Sample records for early onset form

  1. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

    PubMed

    Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

    2017-10-26

    To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

  2. The link between early onset drinking and early onset alcohol-impaired driving in young males.

    PubMed

    Zhang, Lening; Wieczorek, William F; Welte, John W

    2014-05-01

    Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

  3. THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

    PubMed Central

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2014-01-01

    Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

  4. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Early- versus Late-Onset Dysthymia

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

  6. [Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

    PubMed

    Naruse, S; Tsuji, S; Miyatake, T

    1992-09-01

    Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

  7. Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

    PubMed

    Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

    2008-11-01

    To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (onset asthma with risk increasing with the number of adversities experienced (HRs = 1.49-1.71). Early-onset depressive and anxiety disorders also predicted adult-onset asthma (HRs = 1.67-2.11). Childhood adversities and early-onset depressive and anxiety disorders both predicted adult-onset asthma after mutual adjustment (HRs = 1.43-1.91). Childhood adversities and early-onset depressive/anxiety disorders independently predict adult-onset asthma, suggesting that the mental disorder-asthma relationship is not a function of a shared background of childhood adversity.

  8. Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

    PubMed Central

    Vyas, Nora S.; Gogtay, Nitin

    2012-01-01

    Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

  9. Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.

    PubMed

    Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin; Black, Kathleen; Fernandez, Maria Victoria; Budde, John; Ibanez, Laura; Deming, Yuetiva; Kapoor, Manav; Tosto, Giuseppe; Mayeux, Richard P; Holtzman, David M; Fagan, Anne M; Morris, John C; Bateman, Randall J; Goate, Alison M; Harari, Oscar

    2018-02-01

    To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10 -7 ) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10 -7 ) and sLOAD (OR = 1.40; P = 1.21 × 10 -3 ). The PRS was associated with cerebrospinal fluid ptau 181 -Aβ 42 on eADAD (P = 4.36 × 10 -2 ). Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  10. Early- versus Late-Onset Systemic Sclerosis

    PubMed Central

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  11. Hippocampal Morphology and Distinguishing Late-Onset From Early-Onset Elderly Depression

    PubMed Central

    Ballmaier, Martina; Narr, Katherine L.; Toga, Arthur W.; Elderkin-Thompson, Virginia; Thompson, Paul M.; Hamilton, Liberty; Haroon, Ebrahim; Pham, Daniel; Heinz, Andreas; Kumar, Anand

    2010-01-01

    Objective Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual’s hippocampal surface model, between groups. Results Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1–CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects. Conclusions More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. PMID:17986679

  12. Adverse Housing Conditions and Early-Onset Delinquency.

    PubMed

    Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

    2017-09-01

    Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

  13. CDKL5 and ARX mutations in males with early-onset epilepsy.

    PubMed

    Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

    2013-05-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. CDKL5 and ARX mutations in males with early-onset epilepsy

    PubMed Central

    Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Marsh, Eric D.; Berry-Kravis, Elizabeth M.; Medne, Livija; Grix, Art; Wirrell, Elaine C.; Powell, Berkley R.; Nickels, Katherine C.; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B.; Das, Soma

    2013-01-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only ten males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy. PMID:23583054

  15. Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

    PubMed

    Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

    2009-07-15

    Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

  16. Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

    ERIC Educational Resources Information Center

    Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

  17. Lost human capital from early-onset chronic depression.

    PubMed

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  18. Disease evolution in late-onset and early-onset systemic lupus erythematosus.

    PubMed

    Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

    2017-10-01

    Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

  19. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism.

    PubMed

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María; Cobb, Jeff; Planet, Evarist; Cooper, Diane; Pazderska, Agnieszka; Wanic, Krzystof; O'Hanlon, Declan; Gomez, Antonio; de la Ballina, Laura R; Esteller, Manel; Palacin, Manuel; O'Gorman, Donal J; Nolan, John J; Zorzano, Antonio

    2017-10-23

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes.

  20. Are early-onset cannabis smokers at an increased risk of depression spells?

    PubMed

    Fairman, Brian J; Anthony, James C

    2012-04-01

    A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

  1. Are early-onset cannabis smokers at an increased risk of depression spells?

    PubMed Central

    Fairman, Brian J.; Anthony, James C.

    2012-01-01

    Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

  2. Genetics Home Reference: early-onset primary dystonia

    MedlinePlus

    ... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

  3. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

    PubMed Central

    Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

    2018-01-01

    Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

  4. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

    PubMed

    Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

    In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

  5. Evidence for a genetic etiology of early-onset delinquency.

    PubMed

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  6. Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections

    PubMed Central

    Hansen, Nellie I.; Schrag, Stephanie J.; Hale, Ellen; Van Meurs, Krisa; Sánchez, Pablo J.; Cantey, Joseph B.; Faix, Roger; Poindexter, Brenda; Goldberg, Ronald; Bizzarro, Matthew; Frantz, Ivan; Das, Abhik; Benitz, William E.; Shane, Andi L.; Higgins, Rosemary; Stoll, Barbara J.

    2016-01-01

    BACKGROUND: Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth. METHODS: Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006–2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. RESULTS: Early-onset infections were diagnosed in 389 of 396 586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence. CONCLUSIONS: Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected

  7. Early onset marfan syndrome: Atypical clinical presentation of two cases

    PubMed Central

    Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

    2015-01-01

    Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

  8. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

    This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

  9. Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

    PubMed

    Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

    2008-03-15

    Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

  10. Obstetrical outcomes in patients with early onset gestational diabetes.

    PubMed

    Gupta, Simi; Dolin, Cara; Jadhav, Ashwin; Chervenak, Judith; Timor-Tritsch, Ilan; Monteagudo, Ana

    2016-01-01

    The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p < 0.05 was used for significance. Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.

  11. Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

    PubMed Central

    2013-01-01

    Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p < 0.05 for all comparisons). At 18 + 0 to 20 + 0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p = 0.0007, 95% CI 99.0-100.0). At 26 + 0 to 28 + 0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset

  12. Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

    PubMed

    Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

    2015-07-01

    Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Unusual early-onset Huntingtons disease.

    PubMed

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  14. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  15. Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

    PubMed

    Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

    2013-11-01

    Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Comparing Characteristics of Early-Onset Injection Drug Users to Those With Late-Onset Injection in Kermanshah, Iran.

    PubMed

    Jorjoran Shushtari, Zahra; Noroozi, Alireza; Mirzazadeh, Ali; Ahounbar, Elahe; Hajbi, Ahmad; Najafi, Mohammad; Bazrafshan, Ali; Farhadi, Mohammad Hossin; Farhoudian, Ali; Higgs, Peter; Shahboulagh, Farahnaz Mohammadi; Waye, Katherine; Noroozi, Mehdi

    2017-05-12

    Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran. In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses. Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04). Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

  17. Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

    PubMed

    Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

    2004-03-01

    Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the

  18. Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

    PubMed

    Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

    2005-08-01

    Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

  19. Blood-Based Biomarkers of Early-Onset Breast Cancer

    DTIC Science & Technology

    2015-10-01

    n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

  20. [Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

    PubMed

    Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

    2016-07-01

    Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

  1. Early childhood predictors of early onset of smoking: a birth prospective study.

    PubMed

    Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

    2013-10-01

    Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Does Diagnostic Classification of Early-Onset Psychosis Change over Follow-Up?

    ERIC Educational Resources Information Center

    Fraguas, David; de Castro, Maria J.; Medina, Oscar; Parellada, Mara; Moreno, Dolores; Graell, Montserrat; Merchan-Naranjo, Jessica; Arango, Celso

    2008-01-01

    Objective: To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year follow-up period. Methods: A total of 24 patients (18 males (75%) and 6 females (25%), mean age [plus or minus] SD: 15.7 [plus or minus] 1.6 years) with a first episode of EOP formed the sample. Psychotic symptoms…

  3. Intraspinal anomalies in early-onset idiopathic scoliosis.

    PubMed

    Pereira, E A C; Oxenham, M; Lam, K S

    2017-06-01

    In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

  4. EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

    PubMed Central

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2011-01-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

  5. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

    ... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

  6. Early onset obsessive-compulsive disorder with and without tics.

    PubMed

    de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

    2009-07-01

    Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

  7. Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

    PubMed

    Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

    2010-08-01

    The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents

    PubMed Central

    Pacheco, Lorena Sonia; Blanco, Estela; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy

    2017-01-01

    Introduction Obesity and metabolic syndrome (MetS) indicators have increased globally among the pediatric population. MetS indicators in the young elevate their risk of cardiovascular disease and metabolic disorders later in life. This study examined early onset obesity as a risk factor for MetS risk in adolescence. Methods A cohort of Chilean participants (N = 673) followed from infancy was assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was measured at both time points; blood pressure and fasting blood samples were assessed in adolescence only. Early onset obesity was defined as a World Health Organization z score of 2 standard deviations (SDs) or more for body mass index (BMI) at age 5 years. We used linear regression to examine the association between early onset obesity and adolescent MetS risk z score, adjusting for covariates. Results Eighteen percent of participants had early onset obesity, and 50% of these remained obese in adolescence. Mean MetS risk z score in adolescence was significantly higher among those with early onset obesity than among those without (1.0; SD, 0.8 vs 0.2; SD, 0.8 [P < .001]). In the multivariable model, early onset obesity independently contributed to a higher MetS risk score in adolescence (β = 0.27, P < .001), controlling for obesity status at adolescence and sex, and explained 39% of the variance in MetS risk. Conclusion Early onset obesity as young as age 5 years relates to higher MetS risk. PMID:29023232

  9. Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

    ERIC Educational Resources Information Center

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

    2008-01-01

    Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

  10. Early onset marijuana use is associated with learning inefficiencies.

    PubMed

    Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

    2016-05-01

    Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    ClinicalTrials.gov

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  12. Early intervention for late-onset ornithine transcarbamylase deficiency.

    PubMed

    Fujisawa, Daisuke; Mitsubuchi, Hiroshi; Matsumoto, Shirou; Iwai, Masanori; Nakamura, Kimitoshi; Hoshide, Ryuji; Harada, Nawomi; Yoshino, Makoto; Endo, Fumio

    2015-01-01

    We report the case of a family with late-onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3' end of exon 6 of OTC in the X-chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th-generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late-onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late-onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late-onset OTCD, and family members must be provided with genetic counseling. © 2015 Japan Pediatric Society.

  13. Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

    PubMed Central

    Arango, Celso

    2014-01-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  14. Early- and late-onset Alzheimer disease: Are they the same entity?

    PubMed

    Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

    2018-05-01

    Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Early onset of delinquency and the trajectory of alcohol-impaired driving among young males.

    PubMed

    Zhang, Lening; Wieczorek, William F; Welte, John W

    2011-12-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Differentiating early-onset persistent versus childhood-limited conduct problem youth.

    PubMed

    Barker, Edward D; Maughan, Barbara

    2009-08-01

    Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

  17. Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

    ERIC Educational Resources Information Center

    Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  18. Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study.

    PubMed

    Lin, Jing; Gu, Wei; Hou, Yanyan

    2017-11-07

    To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.

  19. Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    1988-01-01

    Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

  20. Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

    PubMed

    Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

    ♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  1. Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

    PubMed

    Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

    2017-07-01

    This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p < 0.05). The rate of secondary hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p < 0.05). Obesity, waist circumference, and SHBG were significantly associated with serum total testosterone level in all, early-onset, and late-onset T2DM. Both all and early-onset T2DM groups had positive correlations between total testosterone and fasting C-peptide, total cholesterol, triglycerides, and uric acid. Our results indicate that in a population of admission to a large urban hospital in China, the prevalence of hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

  2. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  3. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2015-04-01

    autosomal recessive early-onset Parkinson’s disease and juvenile Parkinson disease , Parkin has been shown to promote intracellular Abeta1–42 clearance [15... Parkinsonism . Conclusions Mutations were found in 6/50 families. The presence of an APOE-4 allele may account for disease status in one affected non...AD_________________ Award Number: W81XWH-12-1-0013 TITLE: Whole Exome Analysis of Early Onset Alzheimer’s Disease PRINCIPAL INVESTIGATOR

  4. Key goals and indicators for successful aging of adults with early-onset disability.

    PubMed

    LaPlante, Mitchell P

    2014-01-01

    Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

    PubMed

    Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

    2009-06-01

    Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

  6. [Clinical characteristics and renal uric acid excretion in early-onset gout patients].

    PubMed

    Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

    2018-03-01

    Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

  7. Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

    PubMed Central

    Jouny, Christophe C.; Bergey, Gregory K.

    2011-01-01

    Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

  8. Early onset dementia in New Zealand Pacific boxers: a case series.

    PubMed

    Payman, Vahid; Yates, Susan; Cullum, Sarah

    2018-05-04

    To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.

  9. Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

    PubMed

    Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

    2009-03-01

    The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis

  10. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

    PubMed

    Hartz, Sarah M; Short, Susan E; Saccone, Nancy L; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gubjartsson, Daniel; Hansel, Nadia N; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R; Teumer, Alexander; Thompson, John R; Vink, Jacqueline M; Vogelzangs, Nicole; Wenzlaff, Angela S; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H; Balmforth, Anthony J; Baumeister, Sebastian E; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W; Boyd, Heather A; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K; Hottenga, Jouke Jan; Jensen, Majken K; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M; Mathias, Rasika A; McNeil, Daniel W; Medland, Sarah E; Montgomery, Grant W; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J; Francks, Clyde; Gejman, Pablo V; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S; Lehtimäki, Terho; Levinson, Douglas F; Marazita, Mary L; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D; Murray, Jeffrey C; Nöthen, Markus M; Penninx, Brenda W; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J; Sanders, Alan R; Schwartz, Ann G; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H-Erich; Amos, Christopher I; Breslau, Naomi; Cannon, Dale S; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G; Stevens, Victoria L; Stitzel, Jerry A; Weiss, Robert B; Kraft, Peter; Bierut, Laura J

    2012-08-01

    Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

  11. Operational Thought in Alzheimer's Disease Early Onset and SDAT.

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

  12. The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

    PubMed

    Yang, M Y; Kim, J M; Kim, G W; Mun, J H; Song, M; Ko, H C; Kim, B S; Kim, H S; Kim, M B

    2017-01-01

    Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. © 2016 European Academy of Dermatology and Venereology.

  13. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

    PubMed

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-09-01

    Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

    PubMed

    Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

    1993-05-01

    Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

  15. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

    Donovan, John E.; Molina, Brooke S. G.

    2011-01-01

    Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

  16. Early Onset Malignancies - Genomic Study of Cancer Disparities

    Cancer.gov

    The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

  17. Early onset type 2 diabetes: risk factors, clinical impact and management

    PubMed Central

    Idris, Iskandar

    2014-01-01

    Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

  18. Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

    PubMed Central

    Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

    2012-01-01

    Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

  19. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

    ERIC Educational Resources Information Center

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

    2007-01-01

    Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

  20. Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

    PubMed

    Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

    2008-02-15

    Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

  1. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    PubMed

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

  2. Common variants at five new loci associated with early-onset inflammatory bowel disease.

    PubMed

    Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

    2009-12-01

    The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

  3. Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.

    PubMed

    Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S; Guetta-Baranes, Tamar; Brookes, Keeley J; Chappell, Sally; Turton, James; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David; Morgan, Kevin

    2018-02-01

    Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer's Project consortium, with association data from 17,008 late-onset Alzheimer's disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Risk of early-onset prostate cancer associated with occupation in the Nordic countries.

    PubMed

    Barry, Kathryn Hughes; Martinsen, Jan Ivar; Alavanja, Michael C R; Andreotti, Gabriella; Blair, Aaron; Hansen, Johnni; Kjærheim, Kristina; Koutros, Stella; Lynge, Elsebeth; Sparèn, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Berndt, Sonja I; Pukkala, Eero

    2017-12-01

    Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. We used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e.g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.05-1.13; p heterogeneity  = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (p heterogeneity >0.05). While our early-onset finding for public safety workers was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  6. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    ERIC Educational Resources Information Center

    Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

    2009-01-01

    Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

  7. Early Onset Marijuana Use Is Associated with Learning Inefficiencies

    PubMed Central

    Schuster, Randi Melissa; Hoeppner, Susanne S.; Evins, A. Eden; Gilman, Jodi M.

    2016-01-01

    Objective Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early-onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Method Forty-eight young adults, aged 18–25, who used marijuana at least once per week and 48 matched non-using controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: ‘early onset’ users (EMJ), who started using marijuana at or before age 16 (n = 27), and ‘late onset’ marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Results Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Conclusions Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. PMID:26986749

  8. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    PubMed Central

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  9. Case report of an atypical early onset X-linked retinoschisis in monozygotic twins.

    PubMed

    Murro, Vittoria; Caputo, Roberto; Bacci, Giacomo Maria; Sodi, Andrea; Mucciolo, Dario Pasquale; Bargiacchi, Sara; Giglio, Sabrina Rita; Virgili, Gianni; Rizzo, Stanislao

    2017-02-24

    X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression. We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G > A (p. Trp96Ter) mutation was detected in both patients. Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy.

  10. Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

    PubMed

    Dorobek, Małgorzata; van der Maarel, Silvère M; Lemmers, Richard J L F; Ryniewicz, Barbara; Kabzińska, Dagmara; Frants, Rune R; Gawel, Malgorzata; Walecki, Jerzy; Hausmanowa-Petrusewicz, Irena

    2015-04-01

    Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy). © The Author(s) 2014.

  11. Early onset epilepsy is associated with increased mortality: a population-based study

    PubMed Central

    Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

  12. Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

    PubMed

    Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

    2014-08-20

    Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating

  13. Neural abnormalities in early-onset and adolescence-onset conduct disorder.

    PubMed

    Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

    2010-07-01

    Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

  14. Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

    PubMed

    Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

    2017-12-07

    Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  15. Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and environmental moderation in a sample of african-american youth.

    PubMed

    Kogan, Steven M; Lei, Man-Kit; Beach, Steven R H; Brody, Gene H; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-Fu

    2014-08-01

    Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. The impact of early-onset cannabis use on functional brain correlates of working memory.

    PubMed

    Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

    2010-08-16

    Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  17. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

    PubMed

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

    2007-08-01

    The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

  18. Distinct breast cancer subtypes in women with early-onset disease across races

    PubMed Central

    Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu, Ru-Liang; Lee, Peng

    2014-01-01

    Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. PMID:25057437

  19. Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

    PubMed

    Immanuel, Jincy; Simmons, David

    2017-10-02

    We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

  20. Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

    PubMed

    Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

    2018-04-01

    This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

  1. Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

    PubMed Central

    Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

  2. Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

    PubMed

    Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

    2017-09-01

    Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

  3. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    ERIC Educational Resources Information Center

    Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

    2010-01-01

    Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

  4. ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

    PubMed

    Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

    2015-01-01

    Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

  5. Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations.

    PubMed

    Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy

    2016-01-01

    Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.

  6. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

    PubMed

    Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

    2016-07-01

    Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Indoor tanning and risk of early-onset basal cell carcinoma

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2011-01-01

    Background Despite a rise in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. Objective Evaluate the association between indoor tanning and early-onset BCC. Methods BCC cases (n=376) and controls with minor benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. Results Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI=1.15-2.48). This association was stronger among women (OR=2.14, 95% CI=1.31-3.47), for multiple BCCs (OR=2.16, 95% CI=1.26-3.70), and for BCCs on the trunk and extremities (OR=2.81, 95% CI=1.57-5.02). Risk increased dose-dependently with years used regular indoor tanning devices (p-trend=0.003), number of overall burns (p-trend=<0.001) and burns to biopsy site (p-trend=<0.001) from indoor tanning. Approximately one-quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. Limitations Potential recall bias of indoor tanning by cases and generalizability of the control population suggest replication in other studies is warranted. Conclusions Indoor tanning was a strong risk factor for early-onset BCC, particularly among women. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial. PMID:22153793

  8. Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

    PubMed

    Wahid, Maryam; Kamran, Mohammad

    2016-01-01

    Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

  9. Does theory of mind performance differ in children with early-onset and regressive autism?

    PubMed

    Matthews, Nicole L; Goldberg, Wendy A; Lukowski, Angela F; Osann, Kathryn; Abdullah, Maryam M; Ly, Agnes R; Thorsen, Kara; Spence, M Anne

    2012-01-01

    A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies. © 2011 Blackwell Publishing Ltd.

  10. Isolated early onset anemia after rh isoimmunization: a unique presentation in 3 neonates.

    PubMed

    Louis, Deepak; Oberoi, Sapna; Sundaram, Venkataseshan; Trehan, Amita

    2010-08-01

    Rh isoimmunization manifesting as isolated early onset neonatal anemia has not been reported. We describe the presentation of 3 infants who manifested with isolated early severe anemia. All the infants presented early (3 to 7 d of age) with severe pallor. None had clinically significant jaundice. Evidence for hemolysis was present in all and their direct antiglobulin test was positive. To reduce the hemolysis, immunoglobulin was administered after which their hemoglobin improved. This report highlights the possibility of early onset anemia without significant jaundice as the sole manifestation of Rh isoimmunization and the possible beneficial role of immunoglobulin in them.

  11. Variants of early-onset restrictive eating disturbances in middle childhood.

    PubMed

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2016-01-01

    This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

  12. Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

    PubMed Central

    Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

    2016-01-01

    HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

  13. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

    PubMed

    Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

    2008-09-23

    To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

  14. Stabilization in early adult-onset myopia with corneal refractive therapy.

    PubMed

    González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

    2016-02-01

    To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

    2008-01-01

    Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

  16. Atypical antipsychotics in the treatment of early-onset schizophrenia

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

  17. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

    PubMed

    Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

    2004-09-30

    There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

  18. Early Identification of Autism: Early Characteristics, Onset of Symptoms, and Diagnostic Stability

    ERIC Educational Resources Information Center

    Webb, Sara Jane; Jones, Emily J. H.

    2009-01-01

    In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also…

  19. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

    PubMed

    Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

    2008-11-01

    Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

  20. Social Status of Adolescents with an Early Onset of Externalizing Behavior: The SNARE Study

    ERIC Educational Resources Information Center

    Franken, Aart; Harakeh, Zeena; Veenstra, Rene; Vollebergh, Wilma; Dijkstra, Jan Kornelis

    2017-01-01

    This study investigated the social status (i.e., popularity, likeability, and friendships) of adolescents with an early onset of externalizing behavior (i.e., alcohol use, tobacco use, and antisocial behavior). Building on Moffitt's dual-taxonomy model, it was hypothesized that early onset adolescents were more popular, but not necessarily more…

  1. Cognitive ability in young adulthood predicts risk of early-onset dementia in Finnish men.

    PubMed

    Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Eriksson, Johan G; Räikkönen, Katri

    2018-06-06

    To test if the Finnish Defence Forces Basic Intellectual Ability Test scores at 20.1 years predicted risk of organic dementia or Alzheimer disease (AD). Dementia was defined as inpatient or outpatient diagnosis of organic dementia or AD risk derived from Hospital Discharge or Causes of Death Registers in 2,785 men from the Helsinki Birth Cohort Study, divided based on age at first diagnosis into early onset (<65 years) or late onset (≥65 years). The Finnish Defence Forces Basic Intellectual Ability Test comprises verbal, arithmetic, and visuospatial subtests and a total score (scores transformed into a mean of 100 and SD of 15). We used Cox proportional hazard models and adjusted for age at testing, childhood socioeconomic status, mother's age at delivery, parity, participant's birthweight, education, and stroke or coronary heart disease diagnosis. Lower cognitive ability total and verbal ability (hazard ratio [HR] per 1 SD disadvantage >1.69, 95% confidence interval [CI] 1.01-2.63) scores predicted higher early-onset any dementia risk across the statistical models; arithmetic and visuospatial ability scores were similarly associated with early-onset any dementia risk, but these associations weakened after covariate adjustments (HR per 1 SD disadvantage >1.57, 95% CI 0.96-2.57). All associations were rendered nonsignificant when we adjusted for participant's education. Cognitive ability did not predict late-onset dementia risk. These findings reinforce previous suggestions that lower cognitive ability in early life is a risk factor for early-onset dementia. © 2018 American Academy of Neurology.

  2. Early-Onset Psychosis in Youth with Intellectual Disability

    ERIC Educational Resources Information Center

    Friedlander, R. I.; Donnelly, T.

    2004-01-01

    Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. Just over one half of the patients had a diagnosis of schizophrenia or schizo-affective disorder. One third…

  3. Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

    PubMed

    Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

    2008-06-01

    There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

  4. Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations.

    PubMed

    Marzin, Pauline; Mignot, Cyril; Dorison, Nathalie; Dufour, Louis; Ville, Dorothée; Kaminska, Anna; Panagiotakaki, Eleni; Dienpendaele, Anne-Sophie; Penniello, Marie-José; Nougues, Marie-Christine; Keren, Boris; Depienne, Christel; Nava, Caroline; Milh, Mathieu; Villard, Laurent; Richelme, Christian; Rivier, Clotilde; Whalen, Sandra; Heron, Delphine; Lesca, Gaëtan; Doummar, Diane

    2018-05-31

    Heterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset dystonia-parkinsonism. Next generation sequencing allowed the description of other phenotypes, including early-onset epileptic encephalopathy in two patients. We report on three more patients carrying ATP1A3 mutations with a close phenotype and discuss the relationship of this phenotype to alternating hemiplegia of childhood. The patients' DNA underwent next generation sequencing. A retrospective analysis of clinical case records is reported. Each of the three patients had an unreported heterozygous de novo sequence variant in ATP1A3. These patients shared a similar phenotype characterized by early-onset attacks of movement disorders, some of which proved to be epileptic, and severe developmental delay. (Hemi)plegic attacks had not been considered before genetic testing. Together with the two previously reported cases, our patients confirm that ATP1A3 mutations are associated with a phenotype combining features of early-onset encephalopathy, epilepsy and dystonic fits, as in the most severe forms of alternating hemiplegia of childhood, but in which (hemi)plegic attacks are absent or only suspected retrospectively. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. [Treatment of early onset scoliosis : How far can we go?].

    PubMed

    Studer, D; Hasler, C C; Schulze, A

    2015-11-01

    Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

  6. Early-Onset X-Linked Retinitis Pigmentosa in a Heterozygous Female Harboring an Intronic Donor Splice Site Mutation in the Retinitis Pigmentosa GTPase Regulator Gene.

    PubMed

    Shifera, Amde Selassie; Kay, Christine Nichols

    2015-01-01

    To report a heterozygous female presenting with an early-onset and severe form of X-linked retinitis pigmentosa (XLRP). This is a case series presenting the clinical findings in a heterozygous female with XLRP and two of her family members. Fundus photography, fundus autofluorescence, ocular coherence tomography, and visual perimetry are presented. The proband reported here is a heterozygous female who presented at the age of 8 years with an early onset and aggressive form of XLRP. The patient belongs to a four-generation family with a total of three affected females and four affected males. The patient was initially diagnosed with retinitis pigmentosa (RP) at the age of 4 years. Genetic testing identified a heterozygous donor splice site mutation in intron 1 (IVS1 + 1G > A) of the retinitis pigmentosa GTPase regulator gene. The father of the proband was diagnosed with RP when he was a young child. The sister of the proband, evaluated at the age of 6 years, showed macular pigmentary changes. Although carriers of XLRP are usually asymptomatic or have a mild disease of late onset, the proband presented here exhibited an early-onset, aggressive form of the disease. It is not clear why some carrier females manifest a severe phenotype. A better understanding of the genetic processes involved in the penetrance and expressivity of XLRP in heterozygous females could assist in providing the appropriate counseling to affected families.

  7. Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

    PubMed

    Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

    2013-12-01

    Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

  8. Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

    PubMed

    Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim

    2016-07-01

    Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

    PubMed

    Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

    2013-12-01

    Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

  10. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  11. Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

    PubMed

    Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

    2017-12-01

    To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

  12. Early impact basins and the onset of plate tectonics. Ph.D. Thesis - Maryland Univ.

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1977-01-01

    The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

  13. Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

    PubMed

    Lin, Yu-Ju; Gau, Susan Shur-Fen

    2017-09-01

    We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

  14. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2016-04-01

    Early Onset Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak...relationship between SORL1, AD, and Parkinsonism . 16 Appendix V: ABCA7 Frameshift Deletion Associated with Alzheimer’s Disease in African Americans...onset Alzheimer disease identified using whole-exome sequencing G. W. Beecham1, B. W. Kunkle1, B. Vardarajan2, P. L. Whitehead1, S . Rolati1, E. R

  15. Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy.

    PubMed

    Sainio, Markus T; Ylikallio, Emil; Mäenpää, Laura; Lahtela, Jenni; Mattila, Pirkko; Auranen, Mari; Palmio, Johanna; Tyynismaa, Henna

    2018-06-01

    We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light ( NEFL ) underlying early-onset Charcot-Marie-Tooth (CMT) disease. Motor neurons were differentiated from induced pluripotent stem cells of a patient with early-onset CMT carrying a novel homozygous nonsense mutation in NEFL . Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. We show that the recessive nonsense mutation causes a nearly total loss of NEFL messenger RNA (mRNA), leading to the complete absence of NEFL protein in patient's cultured neurons. Yet the cultured neurons were able to differentiate and form neuronal networks and neurofilaments. Single-neuron gene expression fingerprinting pinpointed NEFL as the most downregulated gene in the patient neurons and provided data of intermediate filament transcript abundancy and dynamics in cultured neurons. Blocking of nonsense-mediated decay partially rescued the loss of NEFL mRNA. The strict neuronal specificity of neurofilament has hindered the mechanistic studies of recessive NEFL nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism. We propose that the neurofilament accumulation, a common feature of many neurodegenerative diseases, mimics the absence of NEFL seen in recessive CMT if aggregation prevents the proper localization of wild-type NEFL in neurons. Our results suggest that the removal of NEFL as a proposed treatment option is harmful in humans.

  16. Evidence for apolipoprotein E {epsilon}4 association in early-onset Alzheimer`s patients with late-onset relatives

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C.

    1995-12-18

    Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD beforemore » age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.« less

  17. Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

    PubMed

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

    2015-01-01

    After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

  18. Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

    PubMed

    Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie; Tita, Alan T N; Leveno, Kenneth J; Reddy, Uma M; Varner, Michael W; Thorp, John M; Mercer, Brian M; Dinsmoor, Mara J; Ramin, Susan M; Carpenter, Marshall W; Samuels, Philip; Sciscione, Anthony; Tolosa, Jorge E; Saade, George; Sorokin, Yoram

    2018-05-23

    To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

  19. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    PubMed Central

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  20. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    PubMed

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2018-01-01

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

    PubMed

    Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

    2014-11-01

    Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

  2. [Analysis of gene mutation of early onset epileptic spasm with unknown reason].

    PubMed

    Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

    2017-11-02

    Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

  3. Early-onset scoliosis: current treatment.

    PubMed

    Cunin, V

    2015-02-01

    Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

  4. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  5. Deferred and immediate imitation in regressive and early onset autism

    PubMed Central

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2010-01-01

    Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation. PMID:18221343

  6. First impression at stroke onset plays an important role in early hospital arrival.

    PubMed

    Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

    2006-01-01

    Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

  7. Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

    PubMed

    Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

    2018-04-01

    Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  8. Early-onset Major Depressive Disorder in men is associated with childlessness.

    PubMed

    Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

    2010-07-01

    The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

  9. Functional Connectivity of the Amygdala in Early Childhood Onset Depression

    PubMed Central

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

  10. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

    PubMed Central

    Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

    2018-01-01

    Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

  11. Rare variants of the 3’-5’ DNA exonuclease TREX1 in early onset small vessel stroke

    PubMed Central

    McGlasson, Sarah; Rannikmäe, Kristiina; Bevan, Steven; Logan, Clare; Bicknell, Louise S.; Jury, Alexa; Jackson, Andrew P.

    2017-01-01

    Background: Monoallelic and biallelic mutations in the exonuclease TREX1 cause monogenic small vessel diseases (SVD). Given recent evidence for genetic and pathophysiological overlap between monogenic and polygenic forms of SVD, evaluation of TREX1 in small vessel stroke is warranted. Methods: We sequenced the TREX1 gene in an exploratory cohort of patients with lacunar stroke (Edinburgh Stroke Study, n=290 lacunar stroke cases). We subsequently performed a fully blinded case-control study of early onset MRI-confirmed small vessel stroke within the UK Young Lacunar Stroke Resource (990 cases, 939 controls). Results: No patients with canonical disease-causing mutations of TREX1 were identified in cases or controls. Analysis of an exploratory cohort identified a potential association between rare variants of TREX1 and patients with lacunar stroke. However, subsequent controlled and blinded evaluation of TREX1 in a larger and MRI-confirmed patient cohort, the UK Young Lacunar Stroke Resource, identified heterozygous rare variants in 2.1% of cases and 2.3% of controls. No association was observed with stroke risk (odds ratio = 0.90; 95% confidence interval, 0.49-1.65 p=0.74). Similarly no association was seen with rare TREX1 variants with predicted deleterious effects on enzyme function (odds ratio = 1.05; 95% confidence interval, 0.43-2.61 p=0.91). Conclusions: No patients with early-onset lacunar stroke had genetic evidence of a TREX1-associated monogenic microangiopathy. These results show no evidence of association between rare variants of TREX1 and early onset lacunar stroke. This includes rare variants that significantly affect protein and enzyme function. Routine sequencing of the TREX1 gene in patients with early onset lacunar stroke is therefore unlikely to be of diagnostic utility, in the absence of syndromic features or family history. PMID:29387804

  12. Perceptions of stigma among people affected by early- and late-onset Alzheimer's disease.

    PubMed

    Ashworth, Rosalie

    2017-07-01

    The aim of this research was to explore perceptions of stigma among people with early- and late-onset Alzheimer's disease and those who support them, using questionnaires ( n = 44) and semi-structured interviews ( n = 14). Perceived stigma reporting was low in the questionnaires, whereas interviews revealed higher levels of perceived stigma in the form of unpredictable reactions to diagnosis, feeling stupid and ignorance of the condition among the public. Perceived stigma was managed in similar ways across age groups, focusing on 'being the lucky ones'. Results support the need to further tackle stigma and challenge expectations, particularly given the drive to diagnose people and thereby expose them to stigma.

  13. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    ERIC Educational Resources Information Center

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  14. Vitrectomy for epiretinal membrane in adult-onset Coats' disease.

    PubMed

    Kumar, Pradeep; Kumar, Vinod

    2017-10-01

    Coats' disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats' disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats' disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed.

  15. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

    PubMed Central

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  16. [The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

    PubMed

    Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

    2016-07-01

    To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

  17. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    PubMed Central

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  18. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

    PubMed

    Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

    2018-05-16

    To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

  19. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    PubMed Central

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear. PMID:26097750

  20. Study protocol: EXERcise and cognition in sedentary adults with early-ONset dementia (EXERCISE-ON).

    PubMed

    Hooghiemstra, Astrid M; Eggermont, Laura H P; Scheltens, Philip; van der Flier, Wiesje M; Bakker, Jet; de Greef, Mathieu H G; Koppe, Peter A; Scherder, Erik J A

    2012-08-16

    Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. The present study is registered within The Netherlands National Trial Register (ref: NTR2124).

  1. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Baldassano, Robert N; Artis, David; Sonnenberg, Gregory F

    2015-09-01

    Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD occurring before the age of 5 represent a unique form of disease, termed Very Early Onset (VEO)-IBD, which is phenotypically- and genetically-distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies, and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal disease. Here we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation.

  2. Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

    PubMed

    Remröd, C; Sjöström, K; Svensson, A

    2013-08-01

    Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age < 20 years) were significantly more anxious and depressed than patients with late-onset psoriasis. In multiple linear regression models, younger age at onset of psoriasis was a significant determinant of higher scores of four personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  3. Onset of Cooperative Dynamics in an Equilibrium Glass-Forming Metallic Liquid

    DOE PAGES

    Jaiswal, Abhishek; O’Keeffe, Stephanie; Mills, Rebecca; ...

    2016-01-22

    Onset of cooperative dynamics has been observed in many molecular liquids, colloids, and granular materials in the metastable regime on approaching their respective glass or jamming transition points, and is considered to play a significant role in the emergence of the slow dynamics. However, the nature of such dynamical cooperativity remains elusive in multicomponent metallic liquids characterized by complex many-body interactions and high mixing entropy. Herein, we report evidence of onset of cooperative dynamics in an equilibrium glass-forming metallic liquid (LM601: Zr 51Cu 36Ni 4Al 9). This is revealed by deviation of the mean effective diffusion coefficient from its high-temperaturemore » Arrhenius behavior below T A ≈ 1300 K, i.e., a crossover from uncorrelated dynamics above T A to landscape-influenced correlated dynamics below T A. Moreover, the onset/ crossover temperature T A in such a multicomponent bulk metallic glass-forming liquid is observed at approximately twice of its calorimetric glass transition temperature (T g ≈ 697 K) and in its stable liquid phase, unlike many molecular liquids.« less

  4. Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

    PubMed

    Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

    2016-07-01

    There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Alcohol intake and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Zhang, Y; Ferrucci, L.M.; Cartmel, B.; Molinaro, A.M.; Leffell, D.J.; Bale, A.E.; Mayne, S.T.

    2014-01-01

    Background Previous epidemiologic studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) light, this has not been evaluated in existing epidemiologic studies. Objective To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Methods BCC cases (n=380) and controls with benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage during an in-person interview. Self-report data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional multivariate logistic regression in the full sample and in women only. Results There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall (above median intake vs. no regular alcohol intake OR 1.10, 95% CI 0.69-1.73) or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly, intake of red wine, white wine, beer or hard liquor and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (pinteraction=0.003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping confidence intervals. Conclusions Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. PMID:25059635

  6. Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

    ERIC Educational Resources Information Center

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

    Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

  7. Vitrectomy for epiretinal membrane in adult-onset Coats’ disease

    PubMed Central

    Kumar, Pradeep; Kumar, Vinod

    2017-01-01

    Coats’ disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats’ disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats’ disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed. PMID:29044085

  8. Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

    PubMed

    Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

    2018-03-20

    To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

  9. Early-onset restrictive eating disturbances in primary school boys and girls.

    PubMed

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2015-07-01

    This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings.

  10. Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

    2015-01-01

    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

  11. Comparison of early versus late onset familial Mediterranean fever.

    PubMed

    Yasar Bilge, Nazife Sule; Sari, Ismail; Solmaz, Dilek; Senel, Soner; Emmungil, Hakan; Kilic, Levent; Yilmaz Oner, Sibel; Yildiz, Fatih; Yilmaz, Sedat; Ersozlu Bozkirli, Duygu; Aydin Tufan, Muge; Yilmaz, Sema; Yazisiz, Veli; Pehlivan, Yavuz; Bes, Cemal; Yildirim Cetin, Gozde; Erten, Sukran; Gonullu, Emel; Sahin, Fezan; Akar, Servet; Aksu, Kenan; Kalyoncu, Umut; Direskeneli, Haner; Erken, Eren; Sayarlioglu, Mehmet; Cınar, Muhammed; Kasifoglu, Timucin

    2018-04-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. Early (≤ 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey. Of the 2246 patients, 1633 (72.7%) were aged ≤ 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas-like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2. Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  12. Alcohol intake and early-onset basal cell carcinoma in a case-control study.

    PubMed

    Zhang, Y; Ferrucci, L M; Cartmel, B; Molinaro, A M; Leffell, D J; Bale, A E; Mayne, S T

    2014-12-01

    Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. © 2014 British Association of Dermatologists.

  13. Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

    ERIC Educational Resources Information Center

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

  14. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    ERIC Educational Resources Information Center

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  15. A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

    PubMed

    Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

    2012-05-01

    Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baldwin, C.T.; Farrer, L.A.; Adair, R.

    Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. Inmore » this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.« less

  17. Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

    PubMed Central

    2012-01-01

    Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered within The Netherlands

  18. Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

    PubMed

    Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

    2018-03-01

    Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (<60 years), and 125 with a late-onset (≥60 years) depression. Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Maturation, Peer Context, and Indigenous Girls' Early-Onset Substance Use

    ERIC Educational Resources Information Center

    Walls, Melissa L.; Whitbeck, Les B.

    2011-01-01

    This article examines a biosocial model of the impact of puberty on indigenous girls' early-onset substance use by considering the potential mediating role of peer context (i.e., mixed-sex peer groups and substance use prototypes) on the puberty and substance use relationship. Data include responses from 360 girls of a common indigenous cultural…

  20. Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

    PubMed

    Silpa-Archa, Sukhum; Cao, Jennifer H; Boonsopon, Sutasinee; Lee, Joan; Preble, Janine M; Foster, C Stephen

    2017-10-01

    To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

  1. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  2. Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

    ERIC Educational Resources Information Center

    Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

    2009-01-01

    Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

  3. CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

    PubMed

    Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

    2009-11-01

    Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

  4. Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

    PubMed

    Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

    2017-06-21

    In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p <0.001) VO2 cost (rate of oxygen consumed per distance traveled). The EOSQ mean score was 102.2 of a possible 120 points, and the SRS mean score was 4.1 of a possible 5 points. A realistic long-term goal for the management of early-onset scoliosis appears to be spine elongation and maintenance of

  5. Early onset of bilateral brachial plexopathy during mantle radiotherapy for Hodgkin's disease.

    PubMed

    Churn, M; Clough, V; Slater, A

    2000-01-01

    We report a case of brachial plexus neuropathy occurring in a 50-year-old man treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost to the right side of the neck (8 Gy in four fractions). The onset of symptoms was early in the course of treatment and a gradual and almost full recovery was observed over 3 years after completion ofradiotherapy. The diagnosis was supported by electromyography. The temporal relationship of the radiotherapy and the onset of the brachial plexus neuropathy suggests a cause and effect, but this association is rarely reported after mantle radiotherapy. We review the aetiology of this condition and postulate possible mechanisms in this patient.

  6. Alertness and cognitive control: Testing the early onset hypothesis.

    PubMed

    Schneider, Darryl W

    2018-05-01

    Previous research has revealed a peculiar interaction between alertness and cognitive control in selective-attention tasks: Congruency effects are larger on alert trials (on which an alerting cue is presented briefly in advance of the imperative stimulus) than on no-alert trials, despite shorter response times (RTs) on alert trials. One explanation for this finding is the early onset hypothesis, which is based on the assumptions that increased alertness shortens stimulus-encoding time and that cognitive control involves gradually focusing attention during a trial. The author tested the hypothesis in 3 experiments by manipulating alertness and stimulus quality (which were intended to shorten and lengthen stimulus-encoding time, respectively) in an arrow-based flanker task involving congruent and incongruent stimuli. Replicating past findings, the alerting manipulation led to shorter RTs but larger congruency effects on alert trials than on no-alert trials. The stimulus-quality manipulation led to longer RTs and larger congruency effects for degraded stimuli than for intact stimuli. These results provide mixed support for the early onset hypothesis, but the author discusses how data and theory might be reconciled if stimulus quality affects stimulus-encoding time and the rate of evidence accumulation in the decision process. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  7. Fatigue-induced early onset of anticipatory postural adjustments in non-fatigued muscles: support for a centrally mediated adaptation.

    PubMed

    Strang, Adam J; Berg, William P; Hieronymus, Mathias

    2009-08-01

    Muscle fatigue has been shown to result in early onset of anticipatory postural adjustments (APAs) relative to those produced in a non-fatigued state. This adaptation is thought to reflect an attempt to preserve postural stability during a focal movement performed in a fatigued state. It remains unclear, however, whether this adaptation is of central (e.g., central nervous system motor command) or peripheral (e.g., muscle contractile properties), origin. One way to confirm that this adaptation is centrally driven is to identify fatigued-induced early APA onsets in non-fatigued muscles. In this study, APAs were obtained using a rapid bilateral reaching maneuver and recorded via surface electromyography before and after conditions of rest (n = 25) or fatigue (n = 25). Fatigue was generated using isokinetic exercise of the right leg. Results showed that fatigue-induced early APA onsets occurred in fatigued and non-fatigued muscles, confirming that fatigue-induced early APA onset is a centrally mediated adaptation.

  8. Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.

    PubMed

    Hakonen, Anna H; Isohanni, Pirjo; Paetau, Anders; Herva, Riitta; Suomalainen, Anu; Lönnqvist, Tuula

    2007-11-01

    Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit, ophthalmoplegia, intractable epilepsy and elevation of serum transaminases. The liver showed mtDNA depletion, whereas the muscle mtDNA was only slightly affected. Alpers-Huttenlocher syndrome has previously been associated with mutations of polymerase gamma, a replicative polymerase of mtDNA. We show here that recessive mutations of the close functional partner of the polymerase, the Twinkle helicase, can also manifest as early encephalopathy with liver involvement, a phenotype reminiscent of Alpers syndrome, and are a new genetic cause underlying tissue-specific mtDNA depletion.

  9. ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum.

    PubMed

    Bertamino, Marta; Severino, Mariasavina; Grossi, Alice; Rusmini, Marta; Tortora, Domenico; Gandolfo, Carlo; Pederzoli, Silvia; Malattia, Clara; Picco, Paolo; Striano, Pasquale; Ceccherini, Isabella; Di Rocco, Maja

    2018-04-12

    Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by fragmented and mineralized elastic fibers in the mid-dermis of the skin, eye, digestive tract and cardiovascular system. Clinical presentation includes typical skin lesions, ocular angioid streaks, and multisystem vasculopathy. The age of onset varies considerably from infancy to old age, but the diagnosis is usually made in young adults due to frequent absence of pathognomonic skin and ocular manifestations in early childhood. We report two children with PXE presenting with isolated multisystem vasculopathy and early-onset stroke. In the first patient, diagnosis was delayed until typical dermatologic alterations appeared; in the second patient, next-generation sequencing (NGS) study led to early diagnosis and specific follow-up, underlying the crucial role in idiopathic pediatric stroke of early genetic testing using NGS-based panels. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  10. [Knowledge of Andalusian pediatricians and parents about early-onset tooth decay].

    PubMed

    González, E; Pérez-Hinojosa, S; Alarcón, J A; Peñalver, M A

    2015-01-01

    To determine the level of knowledge of pediatricians and parents from Andalucía (southern Spain) about early-onset tooth decay, and to assess if pediatricians provide information to parents about pediatric oral care and visits to the pediatric dentist. A random sample of 113 pediatricians and 112 parents with children under 3 years of age received an anonymous questionnaire comprising 14 items for pediatricians and 16 items for parents, grouped into five blocks: visits to the dentist, oral hygiene, caries, nutritional habits, and treatment of caries. The chi-squared test was used to assess differences between groups. Pediatricians showed deficiencies in their knowledge about visits to the dentist and treatment of caries, however their level of knowledge on oral hygiene, tooth decay and nutritional habits were adequate. Parents showed a low level of knowledge in all aspects of the study, mainly about the treatment of tooth decay. There were no significant differences between pediatricians and parents in the knowledge about visits to the dentist, however pediatricians had more knowledge than the parents about hygiene, tooth decay, nutritional habits and treatment (P<0.001). Most of the parents indicated that pediatricians did not provide them detailed information on oral care, and about the possibility of visiting a pediatric dentist. Andalusian pediatricians should improve their knowledge about early-onset tooth decay, and provide more information to parents about the oral care and the possibility of visiting a pediatric dentist. Parents have a very low level of knowledge about early-onset tooth decay, and particularly about treatment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  11. Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia.

    PubMed

    van Rijn, Bas B; Hoeks, Lette B; Bots, Michiel L; Franx, Arie; Bruinse, Hein W

    2006-09-01

    The aim of this study was to report outcome of subsequent pregnancy after early-onset preeclampsia in first pregnancy, and to evaluate potential risk factors for recurrence of preeclampsia and preterm delivery. Reproductive follow-up data were obtained for women with a history of early-onset preeclampsia, resulting in delivery before 34 weeks of gestation at the University Medical Center Utrecht, The Netherlands, between July 1993 and September 2002. The relative contributions of demographic data, outcome variables of first pregnancy, and common thrombophilias to the recurrence risk of preeclampsia and preterm delivery in subsequent pregnancy, were estimated by Cox proportional hazard models. Subsequent pregnancy outcome data were available for 120 women. Overall, preeclampsia reoccurred in the second pregnancy in 30 women (25%). However, 6 women delivered before 34 weeks of gestation (5%), 20 women between 34 and 37 weeks of gestation (17%), and 94 women after 37 weeks of gestation (78%). Forty-one women (34%) had an uneventful pregnancy. Recurrence rates for preeclampsia or preterm delivery were not related to severity of first pregnancy complications, including delivery before 28 weeks of gestation, occurrence of hemolysis, elevated liver enzymes, and low platelet count syndrome, small-for-gestational age infants, and to hereditary or acquired thrombophilias. Chronic hypertension was related to a higher recurrence risk of preeclampsia in the second pregnancy (hazard ratio 2.1, 95% CI 1.0-4.4), and smoking was related to a higher recurrence risk of preterm birth (hazard ratio 2.4, 95% CI 1.1-5.6). Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia is generally favorable.

  12. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

    PubMed

    Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

    2016-04-01

    Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; <34 weeks), and late-onset (n = 8; >36 weeks) preeclampsia and their controls who delivered preterm (n = 5; <34 weeks) or at term (n = 5; >36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value < 0.05. Quantitative real-time reverse transcriptase PCR was used to verify the results. Western blotting was performed to verify the expressions of secreted genes at the protein level. Six hundred twenty-seven genes were differentially expressed in early-compared with late-onset preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early

  13. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

    PubMed

    Veltman-Verhulst, Susanne M; van Rijn, Bas B; Westerveld, H Egbertine; Franx, Arie; Bruinse, Hein W; Fauser, Bart C J M; Goverde, Angelique J

    2010-01-01

    Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

  14. Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

    PubMed

    Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

    2016-01-01

    The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

  15. Definition, clinical profile, microbiological spectrum, and prognostic factors of early-onset prosthetic valve endocarditis.

    PubMed

    López, Javier; Revilla, Ana; Vilacosta, Isidre; Villacorta, Eduardo; González-Juanatey, Carlos; Gómez, Itziar; Rollán, María Jesús; San Román, José Alberto

    2007-03-01

    There is no agreement in the best cutoff time to distinguish between early- and late- onset prosthetic valve endocarditis (PVE). Our objectives are to define early-onset PVE according to the microbiological spectrum and to analyse the profile and short-term prognosis of this entity. The microbiological profile of 172 non-drug users, who were patients with PVE, were compared according to the time elapsed from surgery among 640 endocarditis diagnosed between 1996 and 2004. There were no differences in the microbiological profile of patients with PVE occurred within 2 months of valve replacement and those accounting between 2 and 12 months. The proportion of coagulase-negative Staphylococci (CNS) was higher during the first year post-intervention (37 vs. 18%, P = 0.005) and Streptococci viridans were more common after 1 year (18 vs. 1%, P = 0.001). The percentage of methicilin-resistant CNS strains was higher before 1 year (77 vs. 30%, P = 0.004). Early-onset PVE represented 38% of all episodes of PVE, CNS being the most frequent isolated microorganisms (37%), most of them methicilin resistant (77%). In-hospital mortality of patients who needed urgent surgery was 46% and elective surgery 25%. Overall, in-hospital mortality was 38% and no differences were seen between surgical and medical groups (32 vs. 45%, P = 0.30). Periannular complications were associated with higher in-hospital mortality (60 vs. 27%, P = 0.007). According to the microbiological profile, the most appropriate cutoff time to distinguish between early- and late-onset PVE was 1 year. Methicilin-resistant CNS are the most frequent pathogens and periannular complications, the only risk factor for in-hospital mortality.

  16. Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

    PubMed

    Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2016-06-01

    We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental

  17. Age of crime onset and psychopathic traits in female juvenile delinquents.

    PubMed

    Pechorro, Pedro; Gonçalves, Rui Abrunhosa; Marôco, João; Nunes, Cristina; Jesus, Saul Neves

    2014-09-01

    The aim of this study was to analyze the role of psychopathic traits in the age of crime onset of female juvenile delinquents. Using a sample of 132 young females from the Juvenile Detention Centers of the Portuguese Ministry of Justice and from schools in the Lisbon region, a group of early crime onset (n = 44), a group of late crime onset (n = 44), and a nondelinquent school group (n = 44) were formed. Results showed that early crime onset participants score higher on psychopathy measures, self-reported delinquency, and crime seriousness than late crime onset participants and school participants. Psychopathic-traits scores were significantly associated with age of crime onset, age at first trouble with the law, and frequency and seriousness of crime. © The Author(s) 2013.

  18. Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

    PubMed

    Mendez, Mario F

    2012-11-01

    Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

  19. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

    PubMed Central

    Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

    2014-01-01

    To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

  20. Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

    PubMed

    Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

    2016-06-01

    It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

  1. Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

    PubMed

    Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

    2013-10-01

    Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

  2. Evaluation of intrapartum antibiotic prophylaxis for the prevention of early-onset group B streptococcal infection.

    PubMed

    Sakata, Hiroshi

    2012-12-01

    We retrospectively assessed the medical records of pregnant women who delivered at Asahikawa Kosei Hospital during a period of 3 years between January 2009 and December 2011 and their neonates. Our prophylactic measures against group B Streptococcus (GBS) infection are based on the Japanese guidelines. More specifically, we performed screening by examining bacterial cultures of vaginal-perianal swabs from pregnant women between gestational weeks 33 and 37. Then, sulbactam/ampicillin (SBT/ABPC) was given at a dose of 1.5 g through a drip intravenous infusion at delivery if pregnant women were screened positive for GBS. For neonates born to GBS carrier women, bacterial cultures of pharyngeal swabs, vernix caseosa, stool, and gastric juice were performed at birth. There were 2,399 deliveries and 2,499 births at our hospital. In 169 of the deliveries (175 of the births), GBS was isolated from specimens obtained from gestational weeks 33-37. According to delivery mode, there were 42 cases of cesarean section (45 births) and 127 cases of vaginal delivery (130 births). The GBS-positive neonates accounted for 4.1 % of all deliveries in pregnant women who tested positive for GBS at gestational weeks 33-37. In neonates born by vaginal delivery, the GBS-positive rate was 5.5 %. Of the 2,499 neonates born at our hospital during a period of 3 years, early-onset GBS infection occurred in 1 neonate. The incidence of early-onset GBS infection was 0.40 per 1,000 live births. From 1997 to 2001 (routine GBS screening of mothers was not performed), there were 2,097 deliveries and 2,166 births. Early-onset GBS infection occurred in 1 neonate during this period; thus, the incidence of early-onset GBS infection was 0.46 per 1,000 live births. There were no significant differences in the two periods. The present prophylactic measures such as screening of maternal GBS carriers and intrapartum antibiotic administration are inadequate to decrease the occurrence of early-onset GBS

  3. New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

    PubMed

    Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

    2017-05-01

    The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

  4. Premature adrenarche: novel lessons from early onset androgen excess.

    PubMed

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  5. Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts.

    PubMed

    Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R

    2012-02-01

    The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (<13 years) patients bearing the greatest burden of disease. Greater comorbidity also significantly increased the risk of having self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

    PubMed

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-04-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

  7. Predictors of Early-Onset Permanent Hearing Loss in Malnourished Infants in Sub-Saharan Africa

    ERIC Educational Resources Information Center

    Olusanya, Bolajoko O.

    2011-01-01

    The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the…

  8. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mullan, M.; Bennett, C.; Figueredo, C.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

  9. Growing rod erosion through the lamina causing spinal cord compression in an 8-year-old girl with early-onset scoliosis.

    PubMed

    Abduljabbar, Fahad H; Waly, Feras; Nooh, Anas; Ouellet, Jean

    2016-09-01

    Early-onset scoliosis often occurs by the age of 5 years and is attributed to many structural abnormalities. Syndromic early-onset scoliosis is considered one of the most aggressive types of early-onset scoliosis. Treatment starts with serial casting and bracing, but eventually most of these patients undergo growth-sparing procedures, such as a single growing rod, dual growing rods, or a vertical expandable titanium prosthetic rib. This case report aimed to describe an unusual complication of erosion of a growing rod through the lamina that caused spinal cord compression in an 8-year-old girl with early-onset scoliosis. This is a case report. A retrospective chart review was used to describe the clinical course and radiographic findings of this case after rod erosion into the spinal canal. The patient underwent successful revision surgery removing the rod without neurologic complications. Patients with syndromic early-onset scoliosis are more prone to progressive curves and severe rotational deformity. We believe that the severe kyphotic deformity in addition to the dysplastic nature of the deformity in this population may predispose them to this unusual complication. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Serial elongation-derotation-flexion casting for children with early-onset scoliosis.

    PubMed

    Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

    2015-12-18

    Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois.

  11. Serial elongation-derotation-flexion casting for children with early-onset scoliosis

    PubMed Central

    Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

    2015-01-01

    Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois. PMID:26716089

  12. Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype.

    PubMed

    Berlin, Nicholas L; Cartmel, Brenda; Leffell, David J; Bale, Allen E; Mayne, Susan T; Ferrucci, Leah M

    2015-12-01

    As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. Copyright © 2015. Published by Elsevier Ltd.

  13. Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

    ERIC Educational Resources Information Center

    Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

    2012-01-01

    Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

  14. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2013-04-01

    FTD), FTD with Parkinsonism , and early-onset Alzheimer Disease (EOAD)-like presentations. Using whole exome capture with subsequent sequencing, we...dementia. The MAPT R406W mutation is associated with EOAD-like symptoms and Parkinsonism without FTD, as well as distinct cognitive courses. KEY...OUTCOMES: Carney RM, Kohli MA, Kunkle BW, Naj AC, Gilbert JR, Züchner S, PERICAK-VANCE MA, Parkinsonism and distinct dementia patterns in a

  15. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  16. Age of onset in social anxiety disorder: Relation to clinical variables and major depression comorbidity.

    PubMed

    Koyuncu, Ahmet; Ertekin, Erhan; Deveci, Erdem; Ertekin, Banu Aslanta; Yüksel, Çagrı; Çelebi, Fahri; Binbay, Zerrin; Demir, Esra Yancar; Tükel, Rasit

    2015-05-01

    The aim of this study was to determine the rates of early- and late-onset social anxiety disorder (SAD) and to investigate the effects of onset time on clinical characteristics and the course of SAD. A total of 377 patients with SAD were assessed using a sociodemographic data form, the Liebowitz Social Anxiety Scale (LSAS), Beck Depression Inventory (BDI), and the Global Assessment of Functioning (GAF). Three hundred patients with SAD onset before age 18 were classified as members of the early-onset group, whereas 77 patients with SAD onset at age ≥ 18 comprised the late-onset group. The 2 groups were compared in terms of sociodemographic and clinical characteristics, comorbidity, and scale scores. The rate of SAD onset before age 18 was 79.6%. Compared with the late-onset group, the early-onset group had a younger age at first depressive episode, higher rate of atypical depression, higher LSAS and BDI scores, and lower GAF scores. In cases of early onset of SAD, symptom severity of both SAD and comorbid depression increased and functionality decreased. It is important to assess and treat SAD patients at a younger age because early-onset SAD may be associated with a more severe course and higher rate of major depression comorbidity.

  17. Identifying anomalously early spring onsets in the CESM large ensemble project

    NASA Astrophysics Data System (ADS)

    Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

    2017-06-01

    Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

  18. Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study

    PubMed Central

    2009-01-01

    Background In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. Methods In the UK, two opportunistic samples (aged 16-45 years), paper-based (n = 976) and online (n = 1117), examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Results Overall, 45.6% of females reported menarche ≤ 12 years and 53.3% of males were categorised as having pubertal onset ≤ 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females) and younger age at time of survey (males). For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs <14 years as well as having a sexual debut and unprotected sex <16 years. Males with earlier pubertal onset were more likely to report fighting and aggressive responses to emotional upset during early adolescence while females were more likely to report being bullied and having taken more time off school. Conclusion Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence. PMID:19958543

  19. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

    PubMed

    Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

    2016-02-01

    To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

  20. High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

    PubMed

    Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

    2018-01-01

    Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

  1. The prevention of early-onset neonatal group B streptococcal disease.

    PubMed

    Money, Deborah M; Dobson, Simon

    2004-09-01

    To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal (GBS) disease. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. A review of the literature through MEDLINE from January 1980 to December 2003, relating to neonatal group B streptococcal infection and a review of the Centers for Disease Control and Prevention recommendations. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Exam. 1. Offer all women screening for group B streptococcal disease at 35 to 37 weeks' gestation with culture done from one swab first to the vagina then to the rectal area. (II-1)2. Treat the following women intrapartum at time of labour or rupture of membranes with IV antibiotics: -all women positive by GBS culture screening done at 35 to 37 weeks (II-2) - any women with an infant previously infected with GBS (II-3) - any women with documented GBS bacteriuria (regardless of level of colony-forming units per mL) in this pregnancy (II-2) 3. Treat women at less than 37 weeks' gestation with IV antibiotics unless there has been a negative GBS vaginal/rectal swab culture within 5 weeks. (II-3) 4. Treat women with intrapartum fever with IV antibiotics (i.e., chorioamnionitis must be treated, but broader spectrum antibiotics would be advised). (II-2) 5. If a woman is GBS-positive by culture screening or by history of bacteriuria, with prelabour rupture of membranes at term, treat with GBS antibiotic prophylaxis and initiate induction of

  2. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

    PubMed

    Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

    2013-03-01

    The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

  3. Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

    PubMed

    Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

    2016-08-01

    Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Football and dementia: A qualitative investigation of a community based sports group for men with early onset dementia.

    PubMed

    Carone, Laura; Tischler, Victoria; Dening, Tom

    2016-11-01

    This study investigates the impact of a weekly group providing sport and physical activities for men with early onset dementia established by Notts County Football in the Community (NCFC). There were three aims: to investigate the effect of early onset dementia on individuals with the condition and their carers; to examine the perceptions of current levels of service provision for people with early onset dementia; and to analyse the impact of the group. Men with dementia (n = 5) attending the sessions, their carers (n = 5), NCFC coaching staff (n = 5) and people organizing/facilitating the sessions (n = 5) were interviewed. Semi-structured interviews explored the participants' experiences of dementia, their opinions on current service provisions and on the sessions. Data were analysed using thematic analysis. Four main themes were found: loss related to the condition of dementia and its impact on relationships ('Loss'); lack of age-appropriate services for people with early onset dementia ('Lack of Resources'); enjoyment and positive anticipation related to the group for all involved ('Enjoyment and Anticipation'); and 'the Notts County Effect' which attributed the success of the sessions to the strong brand of the football club, and to personalized service in a "dementia-free" environment. The NCFC sessions provided a safe low-cost intervention with positive effects upon quality of life for both people with early onset dementia, their carers and the staff involved. This suggests that the service may be valuable to a wider range of people living in different areas. © The Author(s) 2014.

  5. Early-Onset Vemurafenib-Induced DRESS Syndrome.

    PubMed

    Munch, Marion; Peuvrel, Lucie; Brocard, Anabelle; Saint Jean, Mélanie; Khammari, Amir; Dreno, Brigitte; Quereux, Gaelle

    2016-01-01

    Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation. © 2015 S. Karger AG, Basel.

  6. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

    2007-01-01

    Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

  7. Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

    PubMed

    Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

    2010-11-01

    The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

  8. Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis.

    PubMed

    Cusmai, Raffaella; Moavero, Romina; Bombardieri, Roberta; Vigevano, Federico; Curatolo, Paolo

    2011-12-01

    In tuberous sclerosis complex, early seizure onset is associated with high risk of intractable epilepsy and cognitive/behavioral impairment. We retrospectively evaluated the long-term outcome of 44 infants presenting with seizures in the first 12 months who received vigabatrin, and were followed up for at least 3.5 years. At the final evaluation 55% of patients were still having seizures, 80% had intellectual disability, and 30% had autism. Sixty-five percent of children who had been treated earlier with vigabatrin after seizure onset achieved seizure freedom, compared with 24% of subjects who received vigabatrin treatment later (P<0.01). Intellectual disability was present in 61% of the children treated early (group A) and in 100% of the children treated later (group B). Nine percent of group A and 52% of group B had autism (P≈0.001). A shorter gap between seizure onset and start of treatment could reduce the risk of epileptic encephalopathy, minimizing the deleterious effect of seizures, but is not able to completely reverse the tuberous sclerosis complex-associated cognitive impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-Marie-Tooth Syndrome

    PubMed Central

    Auer-Grumbach, M.; Fischer, C.; Papić, L.; John, E.; Plecko, B.; Bittner, R. E.; Bernert, G.; Pieber, T. R.; Miltenberger, G.; Schwarz, R.; Windpassinger, C.; Grill, F.; Timmerman, V.; Speicher, M. R.; Janecke, A. R.

    2011-01-01

    Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

  10. Late onset canonical babbling: a possible early marker of abnormal development.

    PubMed

    Oller, D K; Eilers, R E; Neal, A R; Cobo-Lewis, A B

    1998-11-01

    By their 10th month of life, typically developing infants produce canonical babbling, which includes the well-formed syllables required for meaningful speech. Research suggests that emerging speech or language-related disorders might be associated with late onset of canonical babbling. Onset of canonical babbling was investigated for 1,536 high-risk infants, at about 10-months corrected age. Parental report by open-ended questionnaire was found to be an efficient method for ascertaining babbling status. Although delays were infrequent, they were often associated with genetic, neurological, anatomical, and/or physiological abnormalities. Over half the cases of late canonical babbling were not, at the time they were discovered associated with prior significant medical diagnoses. Late canonical-babbling onset may be a predictor of later developmental disabilities, including problems in speech, language, and reading.

  11. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

    PubMed Central

    Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

    2013-01-01

    The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. PMID:22872100

  12. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brice, A.; Tardieu, S.; Campion, D.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelicmore » association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.« less

  13. Problem drinking among Flemish students: beverage type, early drinking onset and negative personal & social consequences.

    PubMed

    De Bruyn, Sara; Wouters, Edwin; Ponnet, Koen; Van Damme, Joris; Maes, Lea; Van Hal, Guido

    2018-02-12

    Although alcohol is socially accepted in most Western societies, studies are clear about its associated negative consequences, especially among university and college students. Studies on the relationship between alcohol-related consequences and both beverage type and drinking onset, however, are scarce, especially in a European context. The aim of this research was, therefore, twofold: (1) What is the relationship between beverage type and the negative consequences experienced by students? and (2) Are these consequences determined by early drinking onset? We will examine these questions within the context of a wide range of alcohol-related consequences. The analyses are based on data collected by the inter-university project 'Head in the clouds?', measuring alcohol use among students in Flanders (Belgium). In total, a large dataset consisting of information from 19,253 anonymously participating students was available. Negative consequences were measured using a shortened version of the Core Alcohol and Drug Survey (CADS_D). Data were analysed using negative binomial regression. Results vary depending on the type of alcohol-related consequences: Personal negative consequences occur frequently among daily beer drinkers. However, a high rate of social negative consequences was recorded for both daily beer drinkers and daily spirits drinkers. Finally, early drinking onset was significantly associated with both personal and social negative consequences, and this association was especially strong between beer and spirits drinking onset and social negative consequences. Numerous negative consequences, both personal and social, are related to frequent beer and spirits drinking. Our findings indicate a close association between drinking beer and personal negative consequences as well as between drinking beer and/or spirits and social negative consequences. Similarly, early drinking onset has a major influence on the rates of both personal and social negative consequences

  14. [Treatment of early-onset generalized dystonia by chronic bilateral stimulation of the internal globus pallidus. Apropos of a case].

    PubMed

    Coubes, P; Echenne, B; Roubertie, A; Vayssière, N; Tuffery, S; Humbertclaude, V; Cambonie, G; Claustres, M; Frerebeau, P

    1999-05-01

    Dystonia musculorum deformans is an inherited severe disease, with a wide clinical polymorphism. The most severe clinical forms with early onset carry a high risk of life-threatening complications. In the absence of any efficient medical treatment, bilateral pallidotomy has previously been reported to be of value in the management of this disease. We report the first clinical case of a severe early-onset generalized dystonia dramatically improved by a bilateral stimulation of the internal globus pallidus. In November 1996, we proposed this neurosurgical procedure for a 8-year-old girl, who had suffered since the age of 3 from severe generalized dystonia, and who progressively became totally dependent and bedridden. She had been under sedation and permanent controlled respiratory assistance for the last two months. The etiology of the disease remained unknown (the DYT1 mutation was absent). Under general anesthesia, we bilaterally implanted a four-contacts electrode in the internal globus pallidus, using the Leksell's stereotactic frame and a 1.5 tesla MRI control. A dramatic improvement was noted 6 weeks later and led us to connect the two electrodes to neurostimulators inserted under the abdominal skin.

  15. Early and Real-Time Detection of Seasonal Influenza Onset

    PubMed Central

    Marques-Pita, Manuel

    2017-01-01

    Every year, influenza epidemics affect millions of people and place a strong burden on health care services. A timely knowledge of the onset of the epidemic could allow these services to prepare for the peak. We present a method that can reliably identify and signal the influenza outbreak. By combining official Influenza-Like Illness (ILI) incidence rates, searches for ILI-related terms on Google, and an on-call triage phone service, Saúde 24, we were able to identify the beginning of the flu season in 8 European countries, anticipating current official alerts by several weeks. This work shows that it is possible to detect and consistently anticipate the onset of the flu season, in real-time, regardless of the amplitude of the epidemic, with obvious advantages for health care authorities. We also show that the method is not limited to one country, specific region or language, and that it provides a simple and reliable signal that can be used in early detection of other seasonal diseases. PMID:28158192

  16. Early-onset schizophrenia: Symptoms and social class of origin.

    PubMed

    Gallagher, Bernard J; Jones, Brian J

    2017-09-01

    The genesis of schizophrenia is multifactorial, including biological and environmental risk factors. We tested for an interactive effect between early-onset schizophrenia (EOS) and social class of origins (socioeconomic status (SES)). Data were further analyzed for a possible connection to type of schizophrenic symptoms. Sampling/Methods: Data for the study are taken from the medical records of 642 patients from a large state hospital in the northeastern United States. Clinical assessments were divided into positive and negative symptomatology through application of the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Positive and Negative Syndrome Scale (PANSS). Detailed information about age of onset and SES of origin was obtained through Social Service Assessment interviews. We uncovered a significant impact of EOS among the poor that elevates risk for negative symptomatology. Poor SES alone does not increase the likelihood of EOS, but it magnifies the deleterious effect of EOS on negative symptoms. Future research on these variables may inform the relative contribution of each.

  17. Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity.

    PubMed

    Mazen, I; El-Gammal, M; Abdel-Hamid, M; Farooqi, I S; Amr, K

    2011-04-01

    Congenital deficiency of the leptin receptor is a very rare cause of severe early-onset obesity. To date, only 9 families have been reported in the literature to have mutations in the leptin receptor gene. The clinical features include severe early onset obesity, severe hyperphagia, hypogonadotropic hypogonadism, and T cell and neuroendocrine/metabolic dysfunction. Here we report two cousins with severe early onset obesity and recurrent respiratory tract infections. Their serum leptin levels were elevated but they were within the range predicted by the elevated fat mass in both cousins. Direct sequencing of the entire coding sequence of the leptin receptor gene revealed a novel homozygous missense mutation in exon 6, P316T. The mutation was found in the homozygous form in both cousins and in the heterozygote state in their parents. This mutation was not found in 200 chromosomes from 100 unrelated normal weight control subjects of Egyptian origin using PCR-RFLP analysis. In conclusion, finding this new mutation in the LEPR beside our previous mutation in the LEP gene implies that monogenic obesity syndromes may be common in the Egyptian population owing to the high rates of consanguineous marriages. Further screening of more families for mutations in LEP, LEPR, and MC4 might confirm this assumption. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Facial emotion identification in early-onset and first-episode psychosis: a systematic review with meta-analysis.

    PubMed

    Barkl, Sophie J; Lah, Suncica; Harris, Anthony W F; Williams, Leanne M

    2014-10-01

    Patients with chronic schizophrenia are characterized by deficits in identifying facial expressions of emotion, and these deficits relate to impaired social and occupational function. It is not yet known if these deficits are trait-like and present at the onset of psychosis, preceding a subsequent diagnosis of schizophrenia. Our objective was to systematically review and analyze the extant literature to assess if there is a consistent profile of emotion identification problems in early-onset and first-episode psychosis. We conducted a systematic review and meta-analysis of 12 peer-reviewed studies of facial emotion identification in early-onset and first-episode psychosis, published between 1980 and March 2013. We examined the average mean difference between patients and controls on measures of facial emotion identification. Findings suggest that patients with early-onset and first-episode psychosis have impairment in identifying facial expressions of biologically salient emotion. Across the 12 studies, the onset of psychosis was distinguished by a generalized effect of significantly poorer accuracy for identifying facial expressions of emotion than healthy controls, and this difference had a substantial effect size (d=-0.88, N=378, 95% CI=-1.42 to -0.32). Within this general effect some emotions were also harder for patients to identify than others, with the magnitude of impairment found to be (i) large for disgust, fear and surprise, and (ii) medium for sadness, and happiness. No between groups mean differences were found for anger or neutral facial expressions. Deficits in facial emotion identification are evident at first onset of a psychotic episode. The findings suggest that, over and above a generalized deficit in identifying facial emotion, patients may find some emotions harder to identifying than others. This reflects findings with chronic schizophrenia populations and suggests that emotion identification impairment represents a trait susceptibility

  19. Sensorineural hearing loss--a common finding in early-onset type 2 diabetes mellitus.

    PubMed

    Lerman-Garber, Israel; Cuevas-Ramos, Daniel; Valdés, Samantha; Enríquez, Lorena; Lobato, Marlette; Osornio, Melannie; Escobedo, Ana Rosa; Pascual-Ramos, Virginia; Mehta, Roopa; Ramírez-Anguiano, Jacqueline; Gómez-Pérez, Francisco J

    2012-01-01

    To evaluate the prevalence and potential associations of hearing impairment in patients 30 to 50 years old with diabetes diagnosed before age 40 years-early-onset type 2 diabetes mellitus (T2DM). The study cohorts consisted of 46 consecutive patients with early-onset T2DM and 47 age-matched control subjects with rheumatoid arthritis. All study subjects completed clinical, serologic, and auditory assessments. The patients with T2DM had a mean age of 42 ± 6 years and a mean disease duration of 11 ± 6 years. Microalbuminuria was present in 26.1%, proliferative retinopathy in 26.1%, and symptomatic peripheral neuropathy in 23.9%. The prevalence of unilateral or bilateral hearing loss was significantly higher in the patients with T2DM than in the patients with rheumatoid arthritis (21.7% versus 6.4%, respectively; P = .01). Most cases of hearing loss were mild and involved high or acute tones. After multivariate analysis with adjustment for age, there was a significant association between hearing loss and hemoglobin A1c (odds ratio, 1.3; 95% confidence interval, 1.02 to 1.81; P = .035). In the patients with T2DM, the lengthening of the brainstem response was not significantly increased; however, the wave morphologic features were abnormal and the reproducibility was poor in both ears in 11 patients (24%). Patients with early-onset T2DM and poor glycemic control have an increased prevalence of subclinical hearing loss and impaired auditory brainstem responses. Hearing impairment may be an underrecognized complication of diabetes.

  20. Internet-Delivered, Family-Based Treatment for Early-Onset OCD: A Preliminary Case Series

    PubMed Central

    Comer, Jonathan S.; Furr, Jami M.; Cooper-Vince, Christine E.; Kerns, Caroline E.; Chan, Priscilla T.; Edson, Aubrey L.; Khanna, Muniya; Franklin, Martin E.; Garcia, Abbe M.; Freeman, Jennifer B.

    2014-01-01

    Given the burdens of early-onset obsessive-compulsive disorder (OCD), limitations in the broad availability and accessibility of evidence-based care for affected youth present serious public health concerns. The growing potential for technological innovations to transform care for the most traditionally remote and underserved families holds enormous promise. This article presents the rationale, key considerations, and a preliminary case series for a promising behavioral telehealth innovation in the evidence-based treatment of early-onset OCD. We developed an Internet-based format for the delivery of family-based treatment for early-onset OCD directly to families in their homes, regardless of their geographic proximity to a mental health facility. Videoteleconferencing (VTC) methods were used to deliver real-time cognitive-behavioral therapy centering on exposure and response prevention to affected families. Participants in the preliminary case series included 5 children between the ages of 4 and 8 (MAge = 6.5) who received the Internet-delivered treatment format. All youth completed a full treatment course, all showed OCD symptom improvements and global severity improvements from pre- to posttreatment, all showed at least partial diagnostic response, and 60% no longer met diagnostic criteria for OCD at posttreatment. No participants got worse, and all mothers characterized the quality of services received as “excellent.” The present work adds to a growing literature supporting the potential of VTC and related computer technology for meaningfully expanding the reach of supported treatments for OCD and lays the foundation for subsequent controlled evaluations to evaluate matters of efficacy and engagement relative to standard in-office evidence-based care. PMID:24295036

  1. Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

    PubMed

    Frazier, Jean A; Giuliano, Anthony J; Johnson, Jacqueline L; Yakutis, Lauren; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A; Hooper, Stephen R

    2012-05-01

    To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published

  2. Premorbid Risk Factors for Major Depressive Disorder: Are They Associated With Early Onset and Recurrent Course?

    PubMed Central

    Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

    2014-01-01

    Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age-11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual SNP-based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early-onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset. PMID:25422974

  3. Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy.

    PubMed

    Mei, Davide; Marini, Carla; Novara, Francesca; Bernardina, Bernardo D; Granata, Tiziana; Fontana, Elena; Parrini, Elena; Ferrari, Anna R; Murgia, Alessandra; Zuffardi, Orsetta; Guerrini, Renzo

    2010-04-01

    Mutations of the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause an X-linked encephalopathy with early onset intractable epilepsy, including infantile spasms and other seizure types, and a Rett syndrome (RTT)-like phenotype. Very limited information is available on the frequency and phenotypic spectrum associated with CDKL5 deletions/duplications. We investigated the role of CDKL5 deletions/duplications in causing early onset intractable epilepsy of unknown etiology in girls. We studied 49 girls with early onset intractable epilepsy, with or without infantile spasms, and developmental impairment, for whom no etiologic factors were obvious after clinical examination, brain magnetic resonance imaging (MRI) and expanded screening for inborn errors of metabolism. We performed CDKL5 gene mutation analysis in all and multiplex ligation dependent probe amplification assay (MLPA) in those who were mutation negative. Custom Array-comparative genomic hybridization (CGH), breakpoint polymerase chain reaction (PCR) analysis, and X-inactivation studies were performed in patients in whom MLPA uncovered a genomic alteration. We found CDKL5 mutations in 8.2% (4 of 49) of patients and genomic deletions in 8.2% (4 of 49). Overall, abnormalities of the CDKL5 gene accounted for 16.3% (8 of 49) of patients. CDKL5 gene deletions are an under-ascertained cause of early onset intractable epilepsy in girls. Genetic testing of CDKL5, including both mutation and deletion/duplication analysis, should be considered in this clinical subgroup.

  4. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

    PubMed

    Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

    2018-01-01

    During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Genomic Analyses of Patients With Unexplained Early-Onset Scoliosis.

    PubMed

    Gao, Xiaochong; Gotway, Garrett; Rathjen, Karl; Johnston, Charles; Sparagana, Steven; Wise, Carol A

    2014-09-01

    To test for rare genetic mutations, a cohort of patients with unexplained early-onset scoliosis (EOS) was screened using high-density microarray genotyping. A cohort of patients with adolescent idiopathic scoliosis (AIS) was similarly screened and the results were compared. Patients with scoliosis in infancy or early childhood (EOS) are at high risk for progressive deformity and associated problems including respiratory compromise. Early-onset scoliosis is frequently associated with genetic disorders but many patients present with nonspecific clinical features and without an associated diagnosis. The authors hypothesized that EOS in these patients may be caused by rare genetic mutations detectable by next-generation genomic methods. The researchers identified 24 patients with unexplained EOS from pediatric orthopedic clinics. They genotyped them, along with 39 connecting family members, using the Illumina OmniExpress-12, version 1.0 beadchip. Resulting genotypes were analyzed for chromosomal changes, specifically copy number variation and absence of heterozygosity. They screened 482 adolescent idiopathic scoliosis (AIS) patients and 744 healthy controls, who were similarly genotyped with the same beadchip, for chromosomal changes identified in the EOS cohort. Copy number variation and absence of heterozygosity analyses revealed a genetic diagnosis of chromosome 15q24 microdeletion syndrome in 1 patient and maternal uniparental disomy of chromosome 14 in a second one. Prior genetic testing and clinical evaluations had been negative in both cases. A large novel chromosome 10 deletion was likely causal in a third EOS patient. These mutations identified in the EOS patients were absent in AIS patients and controls, and thus were not associated with AIS or found in asymptomatic individuals. These data underscore the usefulness of updated genetic evaluations including high-density microarray-based genotyping and other next-generation methods in patients with unexplained

  6. [Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism].

    PubMed

    Creten, C; van der Zwaan, S; Blankespoor, R J; Maatkamp, A; Klinkenberg, S; van Kranen-Mastenbroek, V H J M; Nicolai, J; Dhossche, D M; van Os, J; Schieveld, J N M

    2012-01-01

    Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA.

  7. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Campion, D.; Martinez, M.; Babron, M.C.

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrantmore » by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.« less

  8. The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka, Bangladesh: a propensity score matched analysis

    PubMed Central

    2014-01-01

    Background We estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques. Methods We followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria. Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders. Results Of the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115–1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106–1.225). Conclusions Antibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka. PMID:24742087

  9. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

    PubMed

    Athan, E S; Williamson, J; Ciappa, A; Santana, V; Romas, S N; Lee, J H; Rondon, H; Lantigua, R A; Medrano, M; Torres, M; Arawaka, S; Rogaeva, E; Song, Y Q; Sato, C; Kawarai, T; Fafel, K C; Boss, M A; Seltzer, W K; Stern, Y; St George-Hyslop, P; Tycko, B; Mayeux, R

    2001-11-14

    Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.

  10. Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

    PubMed

    Miller, Jennifer; Kranzler, John; Liu, Yijun; Schmalfuss, Ilona; Theriaque, Douglas W; Shuster, Jonathan J; Hatfield, Ann; Mueller, O Thomas; Goldstone, Anthony P; Sahoo, Trilochan; Beaudet, Arthur L; Driscoll, Daniel J

    2006-08-01

    To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

  11. BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico.

    PubMed

    Ruiz-Flores, Pablo; Sinilnikova, Olga M; Badzioch, Michael; Calderon-Garcidueñas, A L; Chopin, Sandrine; Fabrice, Odefrey; González-Guerrero, J F; Szabo, Csilla; Lenoir, Gilbert; Goldgar, David E; Barrera-Saldaña, Hugo A

    2002-12-01

    The entire coding regions of BRCA1 and BRCA2 were screened for mutations by heteroduplex analysis in 51 Mexican breast cancer patients. One BRCA1 and one BRCA2 truncating mutation each was identified in the group of 32 (6%) early-onset breast cancer patients (< or =35 years). Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case. No mutations or rare sequence variants have been identified in two additional families including each an early-onset breast cancer case and an ovarian cancer patient. The two truncating mutations (BRCA1 3857delT; BRCA2 2663-2664insA) and six of the rare variants have never been reported before and may be of country-specific origin. The majority of the alterations appeared to be distinct, with only one of them being observed in more than one family. Copyright 2002 Wiley-Liss, Inc.

  12. Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

    PubMed Central

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2016-01-01

    Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention. PMID:27799753

  13. Global development and adaptive behaviour in children with early-onset epilepsy: a population-based case-control study.

    PubMed

    Reilly, Colin; Atkinson, Patricia; Memon, Ayesha; Jones, Chloe; Dabydeen, Lyvia; Das, Krishna B; Gillberg, Christopher; Neville, Brian G R; Mahoney, J Matthew; Scott, Rod C

    2018-06-03

    There are limited population-based data on global development and adaptive behaviour in children with early-onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early-onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties. The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community-based study involving children (1-7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally-matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices. Forty-eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy-one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non-white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without. Children with early-onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions. Children with early-onset epilepsy are at significant risk of intellectual disability. Developmental

  14. Comparison of Growing Rod Instrumentation Versus Serial Cast Treatment for Early-Onset Scoliosis.

    PubMed

    Johnston, Charles E; McClung, Anna M; Thompson, George H; Poe-Kochert, Connie; Sanders, James O

    2013-09-01

    A comparison of 2 methods of early-onset scoliosis treatment using radiographic measures and complication rates. To determine whether a delaying tactic (serial casting) has comparable efficacy to a surgical method (insertion of growing rod instrumentation [GRI]) in the initial phase of early-onset deformity management. Serial casts are used in experienced centers to delay operative management of curves of surgical magnitude (greater than 50°) in children up to age 6 years. A total of 27 casted patients from 3 institutions were matched with 27 patients from a multicenter database according to age (within 6 months of each other), curve magnitude (within 10° of each other), and diagnosis. Outcomes were compared according to major curve magnitude, spine length (T1-S1), duration and number of treatment encounters, and complications. There was no difference in age (5.5 years) or initial curve magnitude (65°) between groups, which reflects the accuracy of the matching process. Six pairs of patients had neuromuscular diagnoses, 11 had idiopathic deformities, and 10 had syndromic scoliosis. Growing rod instrumentation patients had smaller curves (45.9° vs. 64.9°; p = .002) at follow-up, but there was no difference in absolute spine length (GRI = 32.0 cm; cast = 30.6 cm; p = .26), even though GRI patients had been under treatment for a longer duration (4.5 vs. 2.4 years; p < .0001) and had undergone a mean of 5.5 lengthenings compared with 4.0 casts. Growing rod instrumentation patients had a 44% complication rate, compared with 1 cast complication. Of 27 casted patients, 15 eventually had operative treatment after a mean delay of 1.7 years after casting. Cast treatment is a valuable delaying tactic for younger children with early-onset scoliosis. Spine deformity is adequately controlled, spine length is not compromised, and surgical complications associated with early GRI treatment are avoided. Copyright © 2013 Scoliosis Research Society. Published by Elsevier Inc

  15. Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families.

    PubMed

    Dominguez-Valentin, Mev; Nakken, Sigve; Tubeuf, Hélène; Vodak, Daniel; Ekstrøm, Per Olaf; Nissen, Anke M; Morak, Monika; Holinski-Feder, Elke; Martins, Alexandra; Møller, Pål; Hovig, Eivind

    2018-01-01

    To study the potential contribution of genes other than BRCA1/2, PTEN, and TP53 to the biological and clinical characteristics of multiple early-onset cancers in Norwegian families, including early-onset breast cancer, Cowden-like and Li-Fraumeni-like syndromes (BC, CSL and LFL, respectively). The Hereditary Cancer Biobank from the Norwegian Radium Hospital was used to identify early-onset BC, CSL or LFL for whom no pathogenic variants in BRCA1/2, PTEN, or TP53 had been found in routine diagnostic DNA sequencing. Forty-four cancer susceptibility genes were selected and analyzed by our in-house designed TruSeq amplicon-based assay for targeted sequencing. Protein- and RNA splicing-dedicated in silico analyses were performed for all variants of unknown significance (VUS). Variants predicted as the more likely to affect splicing were experimentally analyzed by minigene assay. We identified a CSL individual carrying a variant in CHEK2 (c.319+2T>A, IVS2), here considered as likely pathogenic. Out of the five VUS (BRCA2, CDH1, CHEK2, MAP3K1, NOTCH3) tested in the minigene splicing assay, only NOTCH3 c.14090C>T (p.Ser497Leu) showed a significant effect on RNA splicing, notably by inducing partial skipping of exon 9. Among 13 early-onset BC, CSL and LFL patients, gene panel sequencing identified a potentially pathogenic variant in CHEK2 that affects a canonical RNA splicing signal. Our study provides new information on genetic loci that may affect the risk of developing cancer in these patients and their families, demonstrating that genes presently not routinely tested in molecular diagnostic settings may be important for capturing cancer predisposition in these families.

  16. 2014 CODEPEH recommendations: Early detection of late onset deafness, audiological diagnosis, hearing aid fitting and early intervention.

    PubMed

    Núñez-Batalla, Faustino; Jáudenes-Casaubón, Carmen; Sequí-Canet, Jose Miguel; Vivanco-Allende, Ana; Zubicaray-Ugarteche, Jose

    2016-01-01

    The latest scientific literature considers early diagnosis of deafness as the key element to define the educational and inclusive prognosis of the deaf child, because it allows taking advantage of the critical period of development (0-4 years). Highly significant differences exist between deaf people who have been stimulated early and those who have received late or improper intervention. Early identification of late-onset disorders requires special attention and knowledge on the part of every childcare professional. Programs and additional actions beyond neonatal screening should be designed and planed to ensure that every child with a significant hearing loss is detected early. For this purpose, the CODEPEH would like to highlight the need for continuous monitoring of children's auditory health. Consequently, CODEPEH has drafted the recommendations included in the present document. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  17. Impact of substance use on the onset and course of early psychosis.

    PubMed

    Verdoux, Hélène; Tournier, Marie; Cougnard, Audrey

    2005-11-01

    The strong comorbidity between psychosis and substance use is already identifiable in early psychosis, raising the question of the direction of the association between substance use and psychosis onset. It has long been considered that this association was explained by the self-medication hypothesis. This hypothesis has been recently challenged by several prospective studies carried out in population-based samples, showing a dose-response relationship between cannabis exposure and risk of psychosis. This association was independent from potential confounding factors such as exposure to other drugs and pre-existence of psychotic symptoms. As a large percentage of subjects from the general population is now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. Hence, reducing exposure to cannabis may contribute to prevention of some incident cases of psychosis. Regarding prognosis, persistent substance misuse after the onset of psychosis has a deleterious impact on clinical outcome. Therapeutic programs for subjects with dual diagnosis should be implemented early in the course of psychosis to maximise their impact on the course of illness.

  18. Reconceptualizing Early and Late Onset: A Life Course Analysis of Older Heroin Users

    ERIC Educational Resources Information Center

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2008-01-01

    Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…

  19. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  20. Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

    PubMed

    Ruoff, J; Borchardt, S; Heuwieser, W

    2017-07-01

    The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Predicting onset of cannabis use in early adolescence: the interrelation between high-intensity pleasure and disruptive behavior. The TRAILS Study.

    PubMed

    Creemers, Hanneke E; van Lier, Pol A C; Vollebergh, Wilma A M; Ormel, Johan; Verhulst, Frank C; Huizink, Anja C

    2009-11-01

    Increased knowledge about the mechanisms by which some individuals are at risk for early onset of cannabis use might contribute to the improvement of prevention efforts. We focus on the roles of early-adolescent high-intensity pleasure, disruptive behavior, and their interplay in the prediction of onset of cannabis use 2 years later. Data from 81% (n = 1,804) of the participants (51.9% girls) of the Tracking Adolescents' Individual Lives Survey (TRAILS), a prospective general population study in the north of The Netherlands, were analyzed. Measures included parent-reported high-intensity pleasure, and parent- and self-reported general disruptive behavior, attention-deficit hyperactivity, oppositional problems, and conduct problems (Child Behavior Checklist/6-18 and Youth Self-Report) at ages 10-12. Onset of cannabis use was assessed at age 12-14 by means of self-reports. Analyses were carried out in Mplus. Early adolescent high-intensity pleasure and disruptive behavior, mainly conduct problems and to some extent attention-deficit hyperactivity, predicted the onset of cannabis use in adolescence. Although we found some mediation by general disruptive behavior, conduct problems, and attention-deficit hyperactivity, the contribution of high-intensity pleasure in predicting the onset of cannabis use was found to be mainly independent from disruptive behavior. The unique contribution of both high-intensity pleasure and disruptive behavior points in the direction of different pathways toward onset of cannabis use.

  2. Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations.

    PubMed

    Giefer, Matthew J; Lowe, Mark E; Werlin, Steven L; Zimmerman, Bridget; Wilschanski, Michael; Troendle, David; Schwarzenberg, Sarah Jane; Pohl, John F; Palermo, Joseph; Ooi, Chee Y; Morinville, Veronique D; Lin, Tom K; Husain, Sohail Z; Himes, Ryan; Heyman, Melvin B; Gonska, Tanja; Gariepy, Cheryl E; Freedman, Steven D; Fishman, Douglas S; Bellin, Melena D; Barth, Bradley; Abu-El-Haija, Maisam; Uc, Aliye

    2017-07-01

    To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (<6, 6-11, and ≥12 years). Between September 2012 and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6 years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or medication use (P < .01). Children with later-onset disease also were more likely to visit the emergency department (P < .05) or have diabetes (P < .01). Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Escherichia coli early-onset sepsis: trends over two decades.

    PubMed

    Mendoza-Palomar, Natalia; Balasch-Carulla, Milena; González-Di Lauro, Sabina; Céspedes, Maria Concepció; Andreu, Antònia; Frick, Marie Antoinette; Linde, Maria Ángeles; Soler-Palacin, Pere

    2017-09-01

    Escherichia coli early-onset sepsis (EOS) is an important cause of mortality and morbidity in neonates, especially in preterm and very low birth weight (VLBW) newborns. The aim of our study was to evaluate potential changes in the clinical and microbiological characteristics of E. coli EOS in our setting. Epidemiological, clinical, and microbiological data from all neonates with proven E. coli EOS from January 1994 to December 2014 were retrospectively collected in a single tertiary care hospital in Barcelona (Spain). Seventy-eight E. coli EOS cases were analyzed. A slight increase in the incidence of E. coli EOS was observed during the study period. VLBW newborns remained the group with higher incidence (10.4 cases per 1000 live births) and mortality (35.3%). Systematic use of PCR increased E. coli EOS diagnosis, mainly in the term newborn group. There was an increase in resistant E. coli strains causing EOS, with especially high resistance to ampicillin and gentamicin (92.8 and 28.6%, respectively). Nonetheless, resistant strains were not associated with poorer clinical outcomes. There is an urgent need to reconsider the empirical therapy used in neonatal EOS, particularly in VLBW newborns. What is Known: • E. coli early-onset sepsis (EOS) and E. coli resistant strains have been described as overall stable but increasing in VLBW neonates (< 1.500 g) in previous studies. What is New: • Our study shows an increasing incidence of E. coli EOS in all age groups, overruling group B Streptoccocus for the last 10 years. E. coli resistant strains also increased equally in all age groups, with high resistance rates to our first line antibiotics (ampicillin and gentamicin). • Empiric antibiotic therapy of EOS, mainly in VLBW newborns, should be adapted to this new scenario.

  4. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

    PubMed

    Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

    2013-06-01

    The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

  5. Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

    PubMed

    Ratbi, Ilham; Jaouad, Imane Cherkaoui; Elorch, Hamza; Al-Sheqaih, Nada; Elalloussi, Mustapha; Lyahyai, Jaber; Berraho, Amina; Newman, William G; Sefiani, Abdelaziz

    2016-10-01

    Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

    NASA Astrophysics Data System (ADS)

    Hasibuan, B. S.

    2018-03-01

    Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

  7. Epidemiology of early-onset dementia: a review of the literature

    PubMed Central

    Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

    2013-01-01

    Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

  8. The Etiology and Clinical Course of Chronic Pancreatitis in Children With Early Onset of the Disease.

    PubMed

    Wejnarska, Karolina; Kolodziejczyk, Elwira; Wertheim-Tysarowska, Katarzyna; Dadalski, Maciej; Sobczynska-Tomaszewska, Agnieszka; Kierkus, Jarosław; Bal, Jerzy; Rygiel, Agnieszka Magdalena; Oracz, Grzegorz

    2016-12-01

    The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P < 0.05) and underwent surgeries more frequently (25.5% vs 8.9%; P < 0.05). It could be associated with significantly longer follow-up in early onset group (median 6 vs 4 years; P < 0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function. Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries.

  9. Understanding Tobacco Use Onset Among African Americans

    PubMed Central

    Colby, Suzanne M.; Lu, Bo; Ferketich, Amy K.

    2016-01-01

    Introduction: Compared to the majority of non-Hispanic white (“white”) cigarette smokers, many African American smokers demonstrate a later age of initiation. The goal of the present study was to examine African American late-onset smoking (ie, regular smoking beginning at age 18 or later) and determine whether late-onset (vs. early-onset) smoking is protective in terms of quit rates and health outcomes. Methods: We used data from the National Survey of Midlife Development in the United States (MIDUS) because the wide age range of participants (20–75 at baseline) allowed the examination of smoking cessation and mortality incidence across the lifespan. Results: Consistent with previous research, results indicated a later average age of smoking onset among African Americans, compared to whites. Disentangling effects of race from age-of-onset, we found that the cessation rate among late-onset African American smokers was 33%, whereas rates for early-onset African American smokers and early- and late-onset white smokers ranged from 52% to 57%. Finally, results showed that among white, low-socioeconomic status (SES) smokers, the hazard rate for mortality was greater among early- versus late-onset smokers; in contrast, among African American smokers (both low- and high-SES) hazard rates for mortality did not significantly differ among early- versus late-onset smokers. Conclusions: Although late (vs. early) smoking onset may be protective for whites, the present results suggest that late-onset may not be similarly protective for African Americans. Tobacco programs and regulatory policies focused on prevention should expand their perspective to include later ages of initiation, in order to avoid widening tobacco-related health disparities. Implications: This study indicates that late-onset smoking is not only the norm among African American adult smokers, but that late- versus early-onset smoking (ie, delaying onset) does not appear to afford any benefits for African

  10. A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

    PubMed

    Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

    2009-02-01

    Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

  11. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants

    PubMed Central

    Flores, Raquel; González, Juan R.; Argente, Jesús; Pérez-Jurado, Luis A.

    2017-01-01

    Obesity is a multifactorial disorder with high heritability (50–75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity

  12. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    PubMed

    Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A

    2017-05-01

    Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  13. IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma

    PubMed Central

    Balaci, Lenuta ; Spada, Maria Cristina ; Olla, Nazario ; Sole, Gabriella ; Loddo, Laura ; Anedda, Francesca ; Naitza, Silvia ; Zuncheddu, Maria Antonietta ; Maschio, Andrea ; Altea, Daniele ; Uda, Manuela ; Pilia, Sabrina ; Sanna, Serena ; Masala, Marco ; Crisponi, Laura ; Fattori, Matilde ; Devoto, Marcella ; Doratiotto, Silvia ; Rassu, Stefania ; Mereu, Simonetta ; Giua, Enrico ; Cadeddu, Natalina Graziella ; Atzeni, Roberto ; Pelosi, Umberto ; Corrias, Adriano ; Perra, Roberto ; Torrazza, Pier Luigi ; Pirina, Pietro ; Ginesu, Francesco ; Marcias, Silvano ; Schintu, Maria Grazia ; Giacco, Gennaro Sergio Del ; Manconi, Paolo Emilio ; Malerba, Giovanni ; Bisognin, Andrea ; Trabetti, Elisabetta ; Boner, Attilio ; Pescollderungg, Lydia ; Pignatti, Pier Franco ; Schlessinger, David ; Cao, Antonio ; Pilia, Giuseppe 

    2007-01-01

    Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF-κB and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma. PMID:17503328

  14. Co-occurring problems of early onset persistent, childhood limited, and adolescent onset conduct problem youth.

    PubMed

    Barker, Edward D; Oliver, Bonamy R; Maughan, Barbara

    2010-11-01

    It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems differentially co-develop with the EOP, CL and AO trajectories across the childhood and adolescent years. Using data from the Avon Longitudinal Study of Parents and Children, an epidemiological, longitudinal cohort of boys and girls, we estimated growth curves for parent-reported hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors conditional on trajectories of conduct problems (i.e., EOP, CL and AO) from ages 4 to 13 years. At ages 7-8 years, DSM-IV-based diagnoses of conduct disorder, oppositional-defiant disorder, attention deficit/hyperactivity disorder (ADHD), anxiety, depression were examined by conduct problems trajectory. Overall, the development of hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors mirrored the development of conduct problems, showing similar trajectories. Results indicated that the problems of EOP youth were persistent across domains, CL youth showed decreased behavior problems while increasing in prosocial behaviors, and AO youth increased in adjustment problems after 10 years of age. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  15. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    PubMed Central

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological

  16. Early Onset Ageing and Service Preparation in People with Intellectual Disabilities: Institutional Managers' Perspective

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M.

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  17. Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate

    PubMed Central

    Soldovieri, Maria Virginia; Ambrosino, Paolo; Mosca, Ilaria; De Maria, Michela; Moretto, Edoardo; Miceli, Francesco; Alaimo, Alessandro; Iraci, Nunzio; Manocchio, Laura; Medoro, Alessandro; Passafaro, Maria; Taglialatela, Maurizio

    2016-01-01

    Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K+ current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies. PMID:27905566

  18. Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Soldovieri, Maria Virginia; Ambrosino, Paolo; Mosca, Ilaria; De Maria, Michela; Moretto, Edoardo; Miceli, Francesco; Alaimo, Alessandro; Iraci, Nunzio; Manocchio, Laura; Medoro, Alessandro; Passafaro, Maria; Taglialatela, Maurizio

    2016-12-01

    Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K + current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP 2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP 2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies.

  19. Early-Onset Chronic Obstructive Pulmonary Disease Is Associated with Female Sex, Maternal Factors, and African American Race in the COPDGene Study

    PubMed Central

    Foreman, Marilyn G.; Zhang, Lening; Murphy, James; Hansel, Nadia N.; Make, Barry; Hokanson, John E.; Washko, George; Regan, Elizabeth A.; Crapo, James D.; Silverman, Edwin K.

    2011-01-01

    Rationale: The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights. Methods: We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n = 70, age < 55 yr, FEV1 < 50% predicted) were compared with older subjects with COPD (n = 306, age > 64 yr, FEV1 < 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P = 0.0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P < 0.0001. Other risk factors included current smoking (56 vs. 17%, P < 0.0001) and self-report of asthma (39 vs. 25%, P = 0.008). Maternal smoking (70 vs. 44%, P = 0.0001) and maternal COPD (23 vs. 12%, P = 0.03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P = 0.0007); maternal COPD, OR, 4.7 (95% CI, 1.3–17; P = 0.02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P = 0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P = 0.03). Conclusions: These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions. PMID:21562134

  20. Gene expression profiling at birth characterizing the preterm infant with early onset infection.

    PubMed

    Hilgendorff, Anne; Windhorst, Anita; Klein, Manuel; Tchatalbachev, Svetlin; Windemuth-Kieselbach, Christine; Kreuder, Joachim; Heckmann, Matthias; Gkatzoflia, Anna; Ehrhardt, Harald; Mysliwietz, Josef; Maier, Michael; Izar, Benjamin; Billion, Andre; Gortner, Ludwig; Chakraborty, Trinad; Hossain, Hamid

    2017-02-01

    Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

  1. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia.

    PubMed

    Steinbart, E J; Smith, C O; Poorkaj, P; Bird, T D

    2001-11-01

    DNA testing of persons at risk for hereditary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alzheimer disease (FAD) exist, and little is know about the personal and social impact of such testing. In a descriptive, observational study, individuals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal dementia with parkinsonism linked to chromosome 17 underwent DNA testing for the genetic mutations previously identified in affected family members. Individuals were followed up for (1/2) to 3 years and were interviewed regarding attitudes toward the testing process and the impact of the results. Twenty-one (8.4%) of 251 persons at risk for FAD or frontotemporal dementia requested genetic testing. The most common reasons for requesting testing were concern about early symptoms of dementia, financial or family planning, and relief from anxiety. Twelve individuals had positive DNA test results, and 6 of these had early symptoms of dementia; 8 had negative results; and 1 has not yet received results. Of 14 asymptomatic individuals completing testing, 13 believed the testing was beneficial. Two persons reported moderate anxiety and 1 reported moderate depression. As expected, persons with negative test results had happier experiences overall, but even they had to deal with ongoing anxiety and depression. Thus far, there have been no psychiatric hospitalizations, suicide attempts, or denials of insurance. Genetic testing in early-onset FAD and frontotemporal dementia can be completed successfully. Most individuals demonstrate effective coping skills and find the testing to be beneficial, but long-term effects remain unknown.

  2. POLE and POLD1 screening in 155 patients with multiple polyps and early-onset colorectal cancer

    PubMed Central

    Esteban-Jurado, Clara; Giménez-Zaragoza, David; Muñoz, Jenifer; Franch-Expósito, Sebastià; Álvarez-Barona, Miriam; Ocaña, Teresa; Cuatrecasas, Miriam; Carballal, Sabela; López-Cerón, María; Marti-Solano, Maria; Díaz-Gay, Marcos; van Wezel, Tom; Castells, Antoni; Bujanda, Luis; Balmaña, Judith; Gonzalo, Victoria; Llort, Gemma; Ruiz-Ponte, Clara; Cubiella, Joaquín; Balaguer, Francesc; Aligué, Rosa; Castellví-Bel, Sergi

    2017-01-01

    Germline mutations in POLE and POLD1 have been shown to cause predisposition to colorectal multiple polyposis and a wide range of neoplasms, early-onset colorectal cancer being the most prevalent. In order to find additional mutations affecting the proofreading activity of these polymerases, we sequenced its exonuclease domain in 155 patients with multiple polyps or an early-onset colorectal cancer phenotype without alterations in the known hereditary colorectal cancer genes. Interestingly, none of the previously reported mutations in POLE and POLD1 were found. On the other hand, among the genetic variants detected, only two of them stood out as putative pathogenic in the POLE gene, c.1359 + 46del71 and c.1420G > A (p.Val474Ile). The first variant, detected in two families, was not proven to alter correct RNA splicing. Contrarily, c.1420G > A (p.Val474Ile) was detected in one early-onset colorectal cancer patient and located right next to the exonuclease domain. The pathogenicity of this change was suggested by its rarity and bioinformatics predictions, and it was further indicated by functional assays in Schizosaccharomyces pombe. This is the first study to functionally analyze a POLE genetic variant outside the exonuclease domain and widens the spectrum of genetic changes in this DNA polymerase that could lead to colorectal cancer predisposition. PMID:28423643

  3. Early-onset neonatal sepsis is associated with a high heart rate during automatically selected stationary periods.

    PubMed

    Nguyen, Nga; Vandenbroucke, Laurent; Hernández, Alfredo; Pham, Tu; Beuchée, Alain; Pladys, Patrick

    2017-05-01

    This study examined the heart rate variability characteristics associated with early-onset neonatal sepsis in a prospective, observational controlled study. Eligible patients were full-term neonates hospitalised with clinical signs that suggested early-onset sepsis and a C-reactive protein of >10 mg/L. Sepsis was considered proven in cases of symptomatic septicaemia, meningitis, pneumonia or enterocolitis. Heart rate variability parameters (n = 16) were assessed from five-, 15- and 30-minute stationary sequences automatically selected from electrocardiographic recordings performed at admission and compared with a control group using the U-test with post hoc Benjamini-Yekutieli correction. Stationary sequences corresponded to the periods with the lowest changes of heart rate variability over time. A total of 40 full-term infants were enrolled, including 14 with proven sepsis. The mean duration of the cardiac cycle length was lower in the proven sepsis group than in the control group (n = 11), without other significant changes in heart rate variability parameters. These durations, measured in five-minute stationary periods, were 406 (367-433) ms in proven sepsis group versus 507 (463-522) ms in the control group (p < 0.05). Early-onset neonatal sepsis was associated with a high mean heart rate measured during automatically selected stationary periods. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial.

    PubMed

    Sessa, Maria; Lorioli, Laura; Fumagalli, Francesca; Acquati, Serena; Redaelli, Daniela; Baldoli, Cristina; Canale, Sabrina; Lopez, Ignazio D; Morena, Francesco; Calabria, Andrea; Fiori, Rossana; Silvani, Paolo; Rancoita, Paola M V; Gabaldo, Michela; Benedicenti, Fabrizio; Antonioli, Gigliola; Assanelli, Andrea; Cicalese, Maria Pia; Del Carro, Ubaldo; Sora, Maria Grazia Natali; Martino, Sabata; Quattrini, Angelo; Montini, Eugenio; Di Serio, Clelia; Ciceri, Fabio; Roncarolo, Maria Grazia; Aiuti, Alessandro; Naldini, Luigi; Biffi, Alessandra

    2016-07-30

    of nine patients [grade 3 in four of five patients]). No serious adverse events related to the medicinal product were reported. Stable, sustained engraftment of gene-corrected HSCs was observed (a median of 60·4% [range 14·0-95·6] lentiviral vector-positive colony-forming cells across follow-up) and the engraftment level was stable during follow-up; engraftment determinants included the duration of absolute neutropenia and the vector copy number of the medicinal product. A progressive reconstitution of ARSA activity in circulating haemopoietic cells and in the cerebrospinal fluid was documented in all patients in association with a reduction of the storage material in peripheral nerve samples in six of seven patients. Eight patients, seven of whom received treatment when presymptomatic, had prevention of disease onset or halted disease progression as per clinical and instrumental assessment, compared with historical untreated control patients with early-onset disease. GMFM scores for six patients up to the last follow-up showed that gross motor performance was similar to that of normally developing children. The extent of benefit appeared to be influenced by the interval between HSC-GT and the expected time of disease onset. Treatment resulted in protection from CNS demyelination in eight patients and, in at least three patients, amelioration of peripheral nervous system abnormalities, with signs of remyelination at both sites. Our ad-hoc findings provide preliminary evidence of safety and therapeutic benefit of HSC-GT in patients with early-onset metachromatic leukodystrophy who received treatment in the presymptomatic or very early-symptomatic stage. The results of this trial will be reported when all 20 patients have achieved 3 years of follow-up. Italian Telethon Foundation and GlaxoSmithKline. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A neonate with intestinal volvulus without malrotation exhibiting early jaundice with a suspected fetal onset.

    PubMed

    Hara, Kaori; Kinoshita, Mari; Kin, Takane; Arimitsu, Takeshi; Matsuzaki, Yohei; Ikeda, Kazushige; Tomita, Hiroshi; Fujino, Akihiro; Kuroda, Tatsuo

    2015-01-01

    Intestinal volvulus without malrotation is a rare disease that causes volvulus of the small intestine despite normal intestinal rotation and fixation. We encountered a neonate with this disease who developed early jaundice and was suspected to have a fetal onset. This patient was characterized by early jaundice complicating intestinal volvulus without malrotation and is considered to have exhibited reduced fetal movement and early jaundice as a result of volvulus, necrosis, and hemorrhage of the small intestine in the fetal period. If abdominal distention accompanied by early jaundice is noted in a neonate, intestinal volvulus without malrotation and associated intraabdominal hemorrhage should be suspected and promptly treated.

  6. Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

    PubMed

    Mishina, Masahiro; Senda, Michio; Kiyosawa, Motohiro; Ishiwata, Kiichi; De Volder, Anne G; Nakano, Hideki; Toyama, Hinako; Oda, Kei-ichi; Kimura, Yuichi; Ishii, Kenji; Sasaki, Touru; Ohyama, Masashi; Komaba, Yuichi; Kobayashi, Shirou; Kitamura, Shin; Katayama, Yasuo

    2003-05-01

    Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

  7. Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer

    PubMed Central

    Pearlman, Rachel; Frankel, Wendy L.; Swanson, Benjamin; Zhao, Weiqiang; Yilmaz, Ahmet; Miller, Kristin; Bacher, Jason; Bigley, Christopher; Nelsen, Lori; Goodfellow, Paul J.; Goldberg, Richard M.; Paskett, Electra; Shields, Peter G.; Freudenheim, Jo L.; Stanich, Peter P; Lattimer, Ilene; Arnold, Mark; Liyanarachchi, Sandya; Kalady, Matthew; Heald, Brandie; Greenwood, Carla; Paquette, Ian; Prues, Marla; Draper, David J.; Lindeman, Carolyn; Kuebler, J. Philip; Reynolds, Kelly; Brell, Joanna M.; Shaper, Amy A.; Mahesh, Sameer; Buie, Nicole; Weeman, Kisa; Shine, Kristin; Haut, Mitchell; Edwards, Joan; Bastola, Shyamal; Wickham, Karen; Khanduja, Karamjit S.; Zacks, Rosemary; Pritchard, Colin C.; Shirts, Brian H.; Jacobson, Angela; Allen, Brian; de la Chapelle, Albert; Hampel, Heather

    2017-01-01

    IMPORTANCE Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. OBJECTIVE To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. DESIGN, SETTING, AND PARTICIPANTS Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. MAIN OUTCOMES AND MEASURES Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. RESULTS In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10

  8. Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

    PubMed

    Carecchio, Miryam; Picillo, Marina; Valletta, Lorella; Elia, Antonio E; Haack, Tobias B; Cozzolino, Autilia; Vitale, Annalisa; Garavaglia, Barbara; Iuso, Arcangela; Bagella, Caterina F; Pappatà, Sabina; Barone, Paolo; Prokisch, Holger; Romito, Luigi; Tiranti, Valeria

    2017-07-01

    Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.

  9. Understanding Tobacco Use Onset Among African Americans.

    PubMed

    Roberts, Megan E; Colby, Suzanne M; Lu, Bo; Ferketich, Amy K

    2016-04-01

    Compared to the majority of non-Hispanic white ("white") cigarette smokers, many African American smokers demonstrate a later age of initiation. The goal of the present study was to examine African American late-onset smoking (ie, regular smoking beginning at age 18 or later) and determine whether late-onset (vs. early-onset) smoking is protective in terms of quit rates and health outcomes. We used data from the National Survey of Midlife Development in the United States (MIDUS) because the wide age range of participants (20-75 at baseline) allowed the examination of smoking cessation and mortality incidence across the lifespan. Consistent with previous research, results indicated a later average age of smoking onset among African Americans, compared to whites. Disentangling effects of race from age-of-onset, we found that the cessation rate among late-onset African American smokers was 33%, whereas rates for early-onset African American smokers and early- and late-onset white smokers ranged from 52% to 57%. Finally, results showed that among white, low-socioeconomic status (SES) smokers, the hazard rate for mortality was greater among early- versus late-onset smokers; in contrast, among African American smokers (both low- and high-SES) hazard rates for mortality did not significantly differ among early- versus late-onset smokers. Although late (vs. early) smoking onset may be protective for whites, the present results suggest that late-onset may not be similarly protective for African Americans. Tobacco programs and regulatory policies focused on prevention should expand their perspective to include later ages of initiation, in order to avoid widening tobacco-related health disparities. This study indicates that late-onset smoking is not only the norm among African American adult smokers, but that late- versus early-onset smoking (ie, delaying onset) does not appear to afford any benefits for African Americans in terms of cessation or mortality. These results

  10. Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity.

    PubMed

    Dehghani, Mohammad Reza; Mehrjardi, Mohammad Yahya Vahidi; Dilaver, Nafi; Tajamolian, Masoud; Enayati, Samaneh; Ebrahimi, Pirooz; Amoli, Mahsa M; Farooqi, Sadaf; Maroofian, Reza

    2018-03-12

    Congenital Leptin receptor (LEPR) deficiency is a rare genetic cause of early-onset morbid obesity characterised by severe early onset obesity, major hyperphagia, hypogonadotropic hypogonadism and immune and neuroendocrine/metabolic dysfunction. We identified a homozygous loss-of-function mutation, NM_002303.5:c.464 T > G; p.(Tyr155*), in the LEPR in an extended consanguineous family with multiple individuals affected by early-onset severe obesity and hyperphagia. Interestingly, the LEPR-deficient adult females have extremely high body mass index (BMI) with hypogonadal infertility, the BMI of the affected males began to decline around the onset of puberty (13-15 years) with fertility being preserved. These findings lead to the speculation that LEPR deficiency may have a gender-specific effect on the regulation of body weight. In order to elucidate gender-specific effects of LEPR deficiency on reproduction further investigations are needed. The limitations of this study are that our conclusion is based on observations of two males and two females. Further LEPR deficient males and females are required for comparison in order to support this finding more confidently. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. [Early onset scoliosis. What are the options?].

    PubMed

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  12. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

    PubMed Central

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

  13. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2014-01-01

    Objectives Tea and coffee are hypothesized to play a protective role in skin carcinogenesis via bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data supports an inverse association with basal cell carcinoma (BCC) more so than for melanoma or squamous cell carcinoma. To understand if tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. Methods BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, gender, and biopsy site. Subjects completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Results Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38–0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared to non-consumers (OR=0.57, 95% CI=0.34–0.95, p-trend=0.037). Conclusions Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages. PMID:24841641

  14. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study.

    PubMed

    Ferrucci, Leah M; Cartmel, Brenda; Molinaro, Annette M; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2014-07-01

    Tea and coffee are hypothesized to play a protective role in skin carcinogenesis through bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data support an inverse association with basal cell carcinoma (BCC), more so than for melanoma or squamous cell carcinoma. To understand whether tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, sex, and biopsy site. Participants completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38-0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared with nonconsumers (OR=0.57, 95% CI=0.34-0.95, P-trend=0.037). Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages.

  15. Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

    PubMed

    Lee, Younggun; Lee, Jung Hwan; Park, Hyung Jun; Choi, Young Chul

    2017-10-01

    The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis. We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy. Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients. Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy. Copyright © 2017 Korean Neurological Association

  16. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    ERIC Educational Resources Information Center

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  17. A Comparison of the Behavioral and Psychological Symptoms of Dementia (BPSD) in Early-Onset and Late-Onset Alzheimer’s Disease - A Study from South East Asia (Kashmir, India)

    PubMed Central

    Mushtaq, Raheel; Pinto, Charles; Hussain, Arshad; Shoib, Sheikh; Shah, Tabindah; Shah, Sahil; Manzoor, Mushbiq; Bhat, Mudassir; Arif, Tasleem

    2016-01-01

    Background A gradual increase in the longevity due to advancement of treatment modalities and a subsequent surge in elderly population in India have led to a growing curiosity in the geriatric age group with Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) represent epiphenomena of AD. However, no comprehensive study has been carried out in South East Asia (Kashmir, India), to assess the behavioral and psychological symptoms in subtypes of AD. Objectives The purpose of this study was to assess BPSD in early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). Material and Methods The study was conducted in the Memory clinic of the postgraduate department of psychiatry, Government Medical College, Kashmir, India from January 2012 to March 2014. The diagnosis of AD patients was done according to NINCDS-ADRDA criteria. A total of 80 patients of AD were screened (40 with age of onset less than 65, and 40 with age of onset greater than 64). Neuropsychiatric inventory (NPI) was the instrument used for evaluating symptoms of BPSD. The data was analyzed using paired t-test. Results The mean age of presentation of EOAD and LOAD was 63.10 years and 84.28 years, respectively, and the difference between the two was found to be statistically significant. The LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances (NBD) than the EOAD group (p ≤.0001). Conclusion The behavioral and psychological symptoms are significantly severe in late onset subtype compared to the early onset subtype of Alzheimer’s disease in the Kashmiri (Indian) population.  PMID:27433404

  18. Influence of Early Onset of Alcohol Use on the Development of Adolescent Alcohol Problems: A Longitudinal Binational Study

    PubMed Central

    Kim, Min Jung; Mason, W. Alex; Herrenkohl, Todd I.; Catalano, Richard F.; Toumbourou, John W.; Hemphill, Sheryl A.

    2016-01-01

    This study examined cross-national similarities in a developmental model linking early age of alcohol use onset to frequent drinking and heavy drinking and alcohol problems 1 and 2 years later in a binational sample of 13-year-old students from 2 states: Washington State, United States, and Victoria, Australia (N = 1,833). A range of individual, family, school, and peer influences were included in analyses to investigate their unique and shared contribution to development of early and more serious forms of alcohol use and harms from misuse. Data were collected annually over a 3-year period from ages 13 to 15. Analyses were conducted using multiple-group structural equation modeling. For both states, early use of alcohol predicted frequent drinking, which predicted alcohol problems. Family protective influences had no direct effects on heavy drinking, nor effects on alcohol harm in either state, whereas school protection directly reduced the risk of heavy drinking in both states. Exposure to antisocial peers and siblings predicted a higher likelihood of heavy drinking and alcohol harm for students in both Washington and Victoria. Implications for the prevention of adolescent alcohol problems are discussed. PMID:27699620

  19. Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues.

    PubMed

    van den Berg, C B; Chaves, I; Herzog, E M; Willemsen, S P; van der Horst, G T J; Steegers-Theunissen, R P M

    2017-01-01

    The placenta is important in providing a healthy environment for the fetus and plays a central role in the pathophysiology of preeclampsia (PE). Fetal and placental developments are influenced by epigenetic programming. There is some evidence that PE is controlled to an altered circadian homeostasis. In a nested case-control study embedded in the Rotterdam Periconceptional Cohort, we obtained placental tissue, umbilical cord leukocytes (UCL), and human umbilical venous endothelial cells of 13 early-onset PE, 16 late-onset PE and 83 controls comprising 36 uncomplicated and 47 complicated pregnancies, i.e. 27 fetal growth restricted and 20 spontaneous preterm birth. To investigate the associations between PE and the epigenetics of circadian clock and clock-controlled genes in placental and newborn tissues, genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation450K BeadChip and a candidate-gene approach using ANCOVA was applied on 939 CpGs of 39 circadian clock and clock-controlled genes. DNA methylation significantly differed in early-onset PE compared with spontaneous preterm birth at 6 CpGs in placental tissue (3.73 E-5 ≤ p ≤ 0.016) and at 21 CpGs in UCL (1.09 E-5 ≤ p ≤ 0.024). In early-onset PE compared with fetal growth restriction 2 CpGs in placental tissue (p < 0.05) and 8 CpGs in uncomplicated controls (4.78 E-5 ≤ p ≤ 0.049) were significantly different. Moreover, significantly different DNA methylation in early-onset PE compared with uncomplicated controls was shown at 6 CpGs in placental tissue (1.36 E-4 ≤ p ≤ 0.045) and 11 CpGs in uncomplicated controls (2.52 E-6 ≤ p ≤ 0.009). No significant associations were shown with late-onset PE between study groups or tissues. The most differentially methylated CpGs showed hypomethylation in placental tissue and hypermethylation in uncomplicated controls. In conclusion, DNA methylation of circadian clock and clock-controlled genes demonstrated most differences in UCL

  20. Characteristics of the spouse caregiving experience: Comparison between early- and late-onset dementia.

    PubMed

    Wawrziczny, Emilie; Berna, Guillaume; Ducharme, Francine; Kergoat, Marie-Jeanne; Pasquier, Florence; Antoine, Pascal

    2017-06-20

    To investigate the characteristics of the caregiving experience according to age at onset of dementia to adapt support programs. Fifty-seven spouse caregivers of persons with early-onset dementia (PEOD) and 93 spouse caregivers of persons with late-onset dementia (PLOD) participated. The characteristics of the caregiving experience were assessed using questionnaires. We compared the two groups according to age at onset of the disease using a multivariate test, Pillai's Trace test. The analysis showed that there were similarities and differences between the two groups of spouse caregivers. All spouse caregivers were confident in their caregiving role and fairly well prepared for future needs and reported mild depressive and anxious symptoms. However, they lacked informal support, had low confidence in requesting respite care and reported effects on their health. Compared to spouse caregivers of PLOD, spouse caregivers of PEOD had more severe perceptions of the cognitive disorders of persons with dementia (PWD) and had a better sense of preparedness and knowledge of services. Spouse caregivers of PLOD were more confident in their ability to control disturbing thoughts. The results suggest that programs should provide information on support networks to improve preparedness for spouse caregivers of PLOD as well as emphasizing positive coping strategies for caregivers of PEOD to maintain good-quality relationships with PWD, which influences the perception of the symptoms. For both groups, family relationships should be considered.

  1. The prevention of early-onset neonatal group B streptococcal disease.

    PubMed

    Money, Deborah; Allen, Victoria M

    2013-10-01

    reduced with induction of labour. (I) There is no evidence to support safe neonatal outcomes with expectant management in this clinical situation. 1. Offer all women screening for colonization with group B streptococcus at 35 to 37 weeks' gestation with culture taken from one swab first to the vagina and then to the rectum (through the anal sphincter). (II-1A) This includes women with planned Caesarean delivery because of their risk of labour or ruptured membranes earlier than the scheduled Caesarean delivery. (II-2B) 2. Because of the association of heavy colonization with early onset neonatal disease, provide intravenous antibiotic prophylaxis for group B streptococcus at the onset of labour or rupture of the membranes to: • any woman positive for group B streptococcus by vaginal/rectal swab culture screening done at 35 to 37 weeks' gestation (II-2B); • any woman with an infant previously infected with group B streptococcus (II-3B); • any woman with documented group B streptococcus bacteriuria (regardless of level of colony-forming units) in the current pregnancy. (II-2A) 3. Manage all women who are < 37 weeks' gestation and in labour or with rupture of membranes with intravenous group B streptococcus antibiotic prophylaxis for a minimum of 48 hours, unless there has been a negative vaginal/rectal swab culture or rapid nucleic acid-based test within the previous 5 weeks. (II-3A) 4. Treat all women with intrapartum fever and signs of chorioamnionitis with broad spectrum intravenous antibiotics targeting chorioamnionitis and including coverage for group B streptococcus, regardless of group B streptococcus status and gestational age. (II-2A) 5. Request antibiotic susceptibility testing on group B streptococcus-positive urine and vaginal/rectal swab cultures in women who are thought to have a significant risk of anaphylaxis from penicillin. (II-1A) 6. If a woman with pre-labour rupture of membranes at ≥ 37 weeks' gestation is positive for group B streptococcus by

  2. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. The suicidal process: age of onset and severity of suicidal behaviour.

    PubMed

    Thompson, Angus H; Dewa, Carolyn S; Phare, Stephanie

    2012-08-01

    The concept of the suicidal process implies a progression from behaviour of relatively low intent to completed suicide. Evidence from the literature has given rise to the speculation that the age of onset of an early form of the suicidal process may be associated with the ultimate seriousness of suicidal behaviour. This study was designed to test the hypothesis that early onset of the first stage of the suicidal process, a wish to die, is associated with increases in the ultimate position along the suicidal process dimension. Questions on the appearance and timing of suicidal process components (a death wish, ideation, plan, or attempt) were embedded in a telephone survey on mental health and addictions in the workforce. Records of those that had experienced suicidal behaviour were examined for the effects on the age of onset of the first death wish as a function of the level of severity of suicidal behaviour, gender, and depression. The findings showed that increases in suicidal intent were associated with lowered age of the first death wish. This pattern held true for depressed and non-depressed persons alike. The results support the notion that the early onset of a supposed precursor of suicidal behaviour, a death wish in this case, adds to its ability to portend more serious problem levels in later stages of life. Furthermore, mood operates independently in its association with the timing of such suicidal behaviour, suggesting that the effect of a relatively youthful appearance of a wish to die cannot be explained by early onset depression.

  4. Fathers' Alcohol and Cannabis Use Disorder and Early Onset of Drug Use by Their Children.

    PubMed

    Henry, Kimberly L

    2017-05-01

    The unique influence of fathers' alcohol and cannabis use disorder on children's onset of use of these same substances has been rarely studied. A clear understanding of family history in this context is important for the development of family-based prevention initiatives aimed at delaying the onset of substance use among children. Prospective, longitudinal, and intergenerational data on 274 father-child dyads were used. Logistic regression models were estimated to assess the association between fathers' lifetime incidence of an alcohol and cannabis use disorder and children's onset of use of these same substances at or before age 15. The children of fathers who met the criteria for a lifetime cannabis use disorder were more likely to initiate use of alcohol (odds ratio = 6.71, 95% CI [1.92, 23.52]) and cannabis (odds ratio = 8.13, 95% CI [2.07, 31.95]) by age 15, when background covariates and presence of a lifetime alcohol use disorder were controlled for. No unique effect of fathers' alcohol use disorder on children's onset of alcohol and cannabis use was observed. Fathers' lifetime cannabis use disorder had a unique and robust association with children's uptake of alcohol and cannabis by age 15. Future research is needed to identify the mediating mechanisms that link fathers' disorder with children's early onset.

  5. [Early detection on the onset of scarlet fever epidemics in Beijing, using the Cumulative Sum].

    PubMed

    Li, Jing; Yang, Peng; Wu, Shuang-sheng; Wang, Xiao-li; Liu, Shuang; Wang, Quan-yi

    2013-05-01

    Based on data related to scarlet fever which was collected from the Disease Surveillance Information Reporting System in Beijing from 2005 to 2011, to explore the efficiency of Cumulative Sum (CUSUM) in detecting the onset of scarlet fever epidemics. Models as C1-MILD (C1), C2-MEDIUM (C2) and C3-ULTRA (C3) were used. Tools for evaluation as Youden's index and detection time were calculated to optimize the parameters and optimal model. Data on 2011 scarlet fever surveillance was used to verify the efficacy of these models. C1 (k = 0.5, H = 2σ), C2 (k = 0.7, H = 2σ), C3 (k = 1.1, H = 2σ) appeared to be the optimal parameters among these models. Youden's index of C1 was 83.0% and detection time being 0.64 weeks, Youden's index of C2 was 85.4% and detection time being 1.27 weeks, Youden's index of C1 was 85.1% and detection time being 1.36 weeks. Among the three early warning detection models, C1 had the highest efficacy. Three models all triggered the signals within 4 weeks after the onset of scarlet fever epidemics. The early warning detection model of CUSUM could be used to detect the onset of scarlet fever epidemics, with good efficacy.

  6. The high prevalence of impulse control behaviors in patients with early-onset Parkinson's disease: A cross-sectional multicenter study.

    PubMed

    Vela, L; Martínez Castrillo, J C; García Ruiz, P; Gasca-Salas, C; Macías Macías, Y; Pérez Fernández, E; Ybot, I; Lopez Valdés, E; Kurtis, M M; Posada Rodriguez, I J; Mata, M; Ruiz Huete, C; Eimil, M; Borrue, C; Del Val, J; López-Manzanares, L; Rojo Sebastian, A; Marasescu, R

    2016-09-15

    In Parkinson's disease patients, impulse control disorders (ICDs) have been associated with younger age and early disease onset, yet the prevalence of ICDs in early-onset Parkinson's disease (EOPD) patients has yet to be studied. Thus, we set out to compare the prevalence of impulse control behaviors (ICBs) in a cohort of EOPD patients with that in age and gender matched healthy controls (HCs), as well as to analyze the association of these symptoms with the use of dopaminergic drugs and other clinical or demographic factors. A cross-sectional, multicenter study was carried out on patients recruited from outpatient Movement Disorder Clinics, assessing ICBs using the short form of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). In addition, depression and quality of life (QoL) were measured, along with other demographic and clinical variables. Of the 87 EOPD patients, 49 (58.3%) displayed an ICB, as did 28 of the 87 HCs (32.9%; p=0.001). Most of the EOPD patients that displayed an ICB (91.8%) were medicated with a dopamine agonist (DA) and accordingly, DA treatment was associated with a 7-fold increased risk of developing an ICB. Patients with ICBs had a higher depression score and a worse QoL. ICBs are much more prevalent in EOPD patients than in HCs and they are associated with DA intake, depression and a worse QoL. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Facial emotion identification in early-onset psychosis.

    PubMed

    Barkl, Sophie J; Lah, Suncica; Starling, Jean; Hainsworth, Cassandra; Harris, Anthony W F; Williams, Leanne M

    2014-12-01

    Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n=34, mean age=14.11, 53% female) and healthy controls (HC, n=42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia.

    PubMed

    Nizyaeva, N V; Kulikova, G V; Nagovitsyna, M N; Kan, N E; Prozorovskaya, K N; Shchegolev, A I; Sukhikh, G T

    2017-07-01

    We studied the expression of microRNA-146a and microRNA-155 in placental villi from 18 women (26-39 weeks of gestation) of reproductive age with early- or late-onset preeclampsia. The reference group consisted of women with physiological pregnancy and full-term gestation and with preterm birth after caesarian section on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ hybridization with digoxigenin on paraffin sections. It was found that the expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi and syncytial knots was lower at late-onset preeclampsia than at physiologic pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early-onset preeclampsia was higher than in group with preterm delivery (p=0.003). However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the expression of microRNA-155 was lower at late-onset preeclampsia in comparison with full-term physiological pregnancy (p=0.005). In addition, the expression of microRNA-146a and microRNA-155 did not increase in the later terms in preeclampsia, while in the reference groups demonstrating gradual increase in the expression of these markers with increasing gestational age. Expression microRNA-146a and microRNA-155 little differed in early- and late-onset preeclampsia. These findings suggest that different variants of preeclampsia are probably characterized by common pathogenetic pathways. Damaged trophoblast cannot maintain of microRNAs synthesis at the required level, which determines the formation of a vicious circle in preeclampsia and further progression of the disease.

  9. Nearwork in early-onset myopia.

    PubMed

    Saw, Seang-Mei; Chua, Wei-Han; Hong, Ching-Ye; Wu, Hui-Min; Chan, Wai-Ying; Chia, Kee-Seng; Stone, Richard A; Tan, Donald

    2002-02-01

    To determine the relationship of nearwork and myopia in young elementary school-age children in Singapore. A cross-sectional study of 1005 school children aged 7 to 9 years was conducted in two schools in Singapore. Cycloplegic autorefraction, keratometry, and biometry measurements were performed. In addition, the parents completed a detailed questionnaire on nearwork activity (books read per week, reading in hours per day and diopter hours [addition of three times reading, two times computer use, and two times video games use in hours per day]). Other risk factors, such as parental myopia, socioeconomic status, and light exposure history, were assessed. In addition to socioeconomic factors, several nearwork indices were associated with myopia in these young children. The multivariate adjusted odds ratio of higher myopia (at least -3.0 D) for children who read more than two books per week was 3.05 (95% confidence interval [CI], 1.80-5.18). However, the odds ratios of higher myopia for children who read more than 2 hours per day or with more than 8 diopter hours (1.50; 95% CI, 0.87-2.55 and 1.04; 95% CI, 0.61-1.78, respectively) were not significant, after controlling for several factors. Children aged 7 to 9 years with a greater current reading exposure were more likely to be myopic. This association of reading and myopia in a young age cohort was greater than the strength of the reading association generally found in older myopic subjects. Whether these results identify an association of early-onset myopia with nearwork activity or other potentially confounding factors is discussed.

  10. Attention capture by contour onsets and offsets: no special role for onsets.

    PubMed

    Watson, D G; Humphreys, G W

    1995-07-01

    In five experiments, we investigated the power of targets defined by the onset or offset of one of an object's parts (contour onsets and offsets) either to guide or to capture visual attention. In Experiment 1, search for a single contour onset target was compared with search for a single contour offset target against a static background of distractors; no difference was found between the efficiency with which each could be detected. In Experiment 2, onsets and offsets were compared for automatic attention capture, when both occurred simultaneously. Unlike in previous studies, the effects of overall luminance change, new-object creation, and number of onset and offset items were controlled. It was found that contour onset and offset items captured attention equally well. However, display size effects on both target types were also apparent. Such effects may have been due to competition for selection between multiple onset and offset stimuli. In Experiments 3 and 4, single onset and offset stimuli were presented simultaneously and pitted directly against one another among a background of static distractors. In Experiment 3, we examined "guided search," for a target that was formed either from an onset or from an offset among static items. In Experiment 4, the onsets and offsets were uncorrelated with the target location. Similar results occurred in both experiments: target onsets and offsets were detected more efficiently than static stimuli which needed serial search; there remained effects of display size on performance; but there was still no advantage for onsets. In Experiment 5, we examined automatic attention capture by single onset and offset stimuli presented individually among static distractors. Again, there was no advantage for onset over offset targets and a display size effect was also present. These results suggest that, both in isolation and in competition, onsets that do not form new objects neither guide nor gain automatic attention more efficiently

  11. Peer and Teacher Effects on the Early Onset of Sexual Intercourse

    PubMed Central

    Brendgen, Mara; Wanner, Brigitte; Vitaro, Frank

    2007-01-01

    Objectives. We examined the links between peer rejection and verbal abuse by a teacher during childhood with the early onset of sexual intercourse and the mediating role of delinquent behavior and low self-esteem in this context. Methods. We assessed 312 students (159 girls) in northwestern Quebec annually from kindergarten through seventh grade. Peer identifications were used to assess peer rejection and verbal abuse by teachers from kindergarten through fourth grade. In seventh grade, self-reports were used to assess delinquent behavior, self-esteem, and having sexual intercourse. Multiple sources were used to assess control variables. Results. Multiple imputation-based linear and logistic regressions showed that peer rejection was indirectly associated with a higher risk of early intercourse by its link with lower self-esteem, but only for girls. Verbal abuse by teachers during childhood was directly associated with a higher risk of early sexual intercourse and indirectly by its link with delinquent behavior. Conclusions. The results underline the importance of both peers and teachers in healthy sexual development among youths, especially for girls, and emphasize the need for targeted health and sexual education programs. PMID:17901435

  12. General Similarities but Consistent Differences Between Early- and Late-Onset Depression Among Korean Adults Aged 40 and Older.

    PubMed

    Park, Jee Eun; Sohn, Ji Hoon; Seong, Su Jeong; Suk, Hye Won; Cho, Maeng Je

    2015-08-01

    Differences in clinical characteristics, symptomatology, and psychiatric comorbidity between early-onset depression (EOD) and late-onset depression (LOD) were examined in a nationwide representative sample. The Korean Composite International Diagnostic Interview was used to investigate psychiatric diagnoses and age of onset. A total of 319 subjects aged 40 years and older with a current major depressive disorder (MDD) were included, and both a continuous and a dichotomous (40 years) age-of-onset indicator were used in the analyses. Despite general similarities between groups, EOD was related to chronic (recurrent and longer episode) and severe (higher lifetime suicidality) clinical features. Hypersomnia and suicidal plans/attempts were associated with EOD, whereas anhedonia was related to LOD. Lifetime generalized anxiety disorder was associated with EOD, whereas dysthymic disorder was related with higher age of MDD onset. This study provides additional evidence of consistent differences between EOD and LOD among middle-aged and older Asians.

  13. Familial Pathways to Early-Onset Suicidal Behavior: Familial and Individual Antecedents of Suicidal Behavior

    PubMed Central

    Melhem, Nadine M.; Brent, David A.; Ziegler, Melissa; Iyengar, Satish; Kolko, David; Oquendo, Maria; Birmaher, Boris; Burke, Ainsley; Zelazny, Jamie; Stanley, Barbara; Mann, J. John

    2013-01-01

    Objective The authors sought to identify clinical predictors of new-onset suicidal behavior in children of parents with a history of mood disorder and suicidal behavior. Method In a prospective study of offspring of parents with mood disorders, 365 offspring (average age, 20 years) of 203 parents were followed for up to 6 years. Offspring with incident suicide attempts or emergency referrals for suicidal ideation or behavior (“incident events”) were compared with offspring without such events on demographic and clinical characteristics. Multivariate analyses were conducted to examine predictors of incident events and predictors of time to incident event. Results Offspring of probands who had made suicide attempts, compared with offspring of parents with mood disorders who had not made attempts, had a higher rate of incident suicide attempts (4.1% versus 0.6%, relative risk=6.5) as well as overall suicidal events (8.3% versus 1.9%, relative risk=4.4). Mood disorder and self-reported impulsive aggression in offspring and a history of sexual abuse and self-reported depression in parents predicted earlier time to, and greater hazard of, an incident suicidal event. Conclusions In offspring of parents with mood disorders, precursors of early-onset suicidal behavior include mood disorder and impulsive aggression as well as parental history of suicide attempt, sexual abuse, and self-reported depression. These results suggest that efforts to prevent the familial transmission of early-onset suicidal behavior by targeting these domains could reduce the morbidity of suicidal behavior in high-risk youths. PMID:17728421

  14. Internalizing and externalizing psychopathology as predictors of cannabis use disorder onset during adolescence and early adulthood.

    PubMed

    Farmer, Richard F; Seeley, John R; Kosty, Derek B; Gau, Jeff M; Duncan, Susan C; Lynskey, Michael T; Lewinsohn, Peter M

    2015-09-01

    Risk-related liabilities associated with the development of cannabis use disorders (CUDs) during adolescence and early adulthood are thought to be established well before the emergence of the index episode. In this study, internalizing and externalizing psychopathology from earlier developmental periods were evaluated as risk factors for CUDs during adolescence and early adulthood. Participants (N = 816) completed 4 diagnostic assessments between the ages 16 and 30, during which current and past CUDs were assessed as well as a full range of psychiatric disorders associated with internalizing and externalizing psychopathology domains. In unadjusted and adjusted time-to-event analyses, externalizing but not internalizing psychopathology from proximal developmental periods predicted subsequent CUD onset. A large proportion of adolescent and early adult cases, however, did not manifest any externalizing or internalizing psychopathology during developmental periods before CUD onset. Findings are consistent with the emerging view that externalizing disorders from proximal developmental periods are robust risk factors for CUDs. Although the identification of externalizing liabilities may aid in the identification of individuals at risk for embarking on developmental pathways that culminate in CUDs, such liabilities are an incomplete indication of overall risk. (c) 2015 APA, all rights reserved).

  15. Inhibitory control and the onset of combustible cigarette, e-cigarette, and hookah use in early adolescence: The moderating role of socioeconomic status.

    PubMed

    Riggs, Nathaniel R; Pentz, Mary Ann

    2016-01-01

    The purpose of the study was to test the moderating influence of socioeconomic status (SES) on the associations between inhibitory control and the onset of combustible cigarette, electronic (e-) cigarette, and hookah use in early adolescence. A total of 407 adolescents self-reported nicotine use, inhibitory control, and SES. The hypothesis that inhibitory control would be significantly associated with nicotine use onset (i.e., combustible cigarettes, e-cigarettes, and hookah) only under the condition of low SES was tested. Direct associations were found for inhibitory control on "ever use" of all three nicotine use variables. A moderating effect was also found whereby low inhibitory control was significantly associated with nicotine use onset when participants were from low, but not high, SES families. Findings illustrate one contextual condition under which inhibitory control is associated with early onset of nicotine use.

  16. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.

    PubMed

    Aziz, Anne-Laure; Giusiano, Bernard; Joubert, Sven; Duprat, Lauréline; Didic, Mira; Gueriot, Claude; Koric, Lejla; Boucraut, José; Felician, Olivier; Ranjeva, Jean-Philippe; Guedj, Eric; Ceccaldi, Mathieu

    2017-06-01

    Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism.

    PubMed

    Podhajska, Agata; Musso, Alessandra; Trancikova, Alzbeta; Stafa, Klodjan; Moser, Roger; Sonnay, Sarah; Glauser, Liliane; Moore, Darren J

    2012-01-01

    Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygous and heterozygous missense mutations in ATP13A2 have been identified in subjects with early-onset parkinsonism. The mechanism(s) by which missense mutations potentially cause parkinsonism are not understood at present. Here, we demonstrate that homozygous F182L, G504R and G877R missense mutations commonly impair the protein stability of ATP13A2 leading to its enhanced degradation by the proteasome. ATP13A2 normally localizes to endosomal and lysosomal membranes in neurons and the F182L and G504R mutations disrupt this vesicular localization and promote the mislocalization of ATP13A2 to the endoplasmic reticulum. Heterozygous T12M, G533R and A746T mutations do not obviously alter protein stability or subcellular localization but instead impair the ATPase activity of microsomal ATP13A2 whereas homozygous missense mutations disrupt the microsomal localization of ATP13A2. The overexpression of ATP13A2 missense mutants in SH-SY5Y neural cells does not compromise cellular viability suggesting that these mutant proteins lack intrinsic toxicity. However, the overexpression of wild-type ATP13A2 may impair neuronal integrity as it causes a trend of reduced neurite outgrowth of primary cortical neurons, whereas the majority of disease-associated missense mutations lack this ability. Finally, ATP13A2 overexpression sensitizes cortical neurons to neurite shortening induced by exposure to cadmium or nickel ions, supporting a functional interaction between ATP13A2 and heavy metals in post-mitotic neurons, whereas missense mutations influence this sensitizing effect. Collectively, our study provides support for common loss-of-function effects of homozygous and heterozygous missense

  18. Common Pathogenic Effects of Missense Mutations in the P-Type ATPase ATP13A2 (PARK9) Associated with Early-Onset Parkinsonism

    PubMed Central

    Podhajska, Agata; Musso, Alessandra; Trancikova, Alzbeta; Stafa, Klodjan; Moser, Roger; Sonnay, Sarah; Glauser, Liliane; Moore, Darren J.

    2012-01-01

    Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygous and heterozygous missense mutations in ATP13A2 have been identified in subjects with early-onset parkinsonism. The mechanism(s) by which missense mutations potentially cause parkinsonism are not understood at present. Here, we demonstrate that homozygous F182L, G504R and G877R missense mutations commonly impair the protein stability of ATP13A2 leading to its enhanced degradation by the proteasome. ATP13A2 normally localizes to endosomal and lysosomal membranes in neurons and the F182L and G504R mutations disrupt this vesicular localization and promote the mislocalization of ATP13A2 to the endoplasmic reticulum. Heterozygous T12M, G533R and A746T mutations do not obviously alter protein stability or subcellular localization but instead impair the ATPase activity of microsomal ATP13A2 whereas homozygous missense mutations disrupt the microsomal localization of ATP13A2. The overexpression of ATP13A2 missense mutants in SH-SY5Y neural cells does not compromise cellular viability suggesting that these mutant proteins lack intrinsic toxicity. However, the overexpression of wild-type ATP13A2 may impair neuronal integrity as it causes a trend of reduced neurite outgrowth of primary cortical neurons, whereas the majority of disease-associated missense mutations lack this ability. Finally, ATP13A2 overexpression sensitizes cortical neurons to neurite shortening induced by exposure to cadmium or nickel ions, supporting a functional interaction between ATP13A2 and heavy metals in post-mitotic neurons, whereas missense mutations influence this sensitizing effect. Collectively, our study provides support for common loss-of-function effects of homozygous and heterozygous missense

  19. The Burden of Invasive Early-Onset Neonatal Sepsis in the United States, 2005–2008

    PubMed Central

    Weston, Emily J.; Pondo, Tracy; Lewis, Melissa M.; Martell-Cleary, Pat; Morin, Craig; Jewell, Brenda; Daily, Pam; Apostol, Mirasol; Petit, Sue; Farley, Monica; Lynfield, Ruth; Reingold, Art; Hansen, Nellie I.; Stoll, Barbara J.; Shane, Andi L.; Zell, Elizabeth; Schrag, Stephanie J.

    2011-01-01

    Background Sepsis in the first 3 days of life is a leading cause of morbidity and mortality among infants. Group B Streptococcus (GBS), historically the primary cause of early-onset sepsis, has declined through widespread use of intrapartum chemoprophylaxis. We estimated the national burden of invasive early-onset sepsis (EOS) cases and deaths in the era of GBS prevention. Methods Population-based surveillance for invasive EOS was conducted in 4 of CDC’s Active Bacterial Core surveillance (ABCs) sites from 2005–2008. We calculated incidence using state and national live birth files. Estimates of the national number of cases and deaths were calculated, standardizing by race and gestational age. Results ABCs identified 658 cases of EOS; 72 (10.9%) were fatal. Overall incidence remained stable during the three years (2005:0.77 cases/1,000 live births; 2008:0.76 cases/1,000 live births). GBS (~38%) was the most commonly reported pathogen followed by Escherichia coli (~24%). Black preterm infants had the highest incidence (5.14 cases/1,000 live births) and case fatality (24.4%). Non-black term infants had the lowest incidence (0.40 cases/1,000 live births) and case fatality (1.6%). The estimated national annual burden of EOS was approximately 3,320 cases (95% CI: 3,060–3,580) including 390 deaths (95% CI: 300–490). Among preterm infants, 1,570 cases (95% CI: 1,400–1,770; 47.3% of the overall) and 360 deaths (95% CI: 280–460; 92.3% of the overall) occurred annually. Conclusions The burden of invasive early-onset sepsis remains substantial in the era of GBS prevention and disproportionately affects preterm and black infants. Identification of strategies to prevent preterm births is needed to reduce the neonatal sepsis burden. PMID:21654548

  20. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

  1. Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

    PubMed

    Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

    2013-11-01

    The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

  2. [Comparision of risk factors and pathogens in patients with early- and late-onset ventilator-associated pneumonia in intensive care unit].

    PubMed

    Liang, Y J; Li, Z L; Wang, L; Liu, B Y; Ding, R Y; Ma, X C

    2017-10-01

    Objective: To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU). Methods: This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital, China Medical University from Jan 2012 to Jun 2016. Subjects were classified by ventilator status: early-onset VAP (< 5 d ventilation, E-VAP) or late-onset VAP (≥ 5 d ventilation, L-VAP). Potential risk factors and pathogen were evaluated. Results: A total of 4 179 patients in adult ICU were screened, 3 989 (95.5%) of whom were mechanically ventilated, 962 patients with mechanical ventilation time ≥ 48 h. VAP developed in 142 patients. E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male ( OR =1.825, 95% CI 1.006-3.310), chronic obstructive pulmonary disease (COPD; OR =3.746, 95% CI 1.795-7.818), emergency intubation ( OR =1.932, 95% CI 1.139-3.276), aspiration ( OR =3.324, 95% CI 1.359-8.130). Whereas independent risk factors for L-VAP were coma ( OR =2.335, 95% CI 1.300-4.194), renal dysfunction ( OR =0.524, 95% CI 0.290-0.947), emergency intubation ( OR =2.184, 95% CI 1.334-3.574). Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2%(19/63)vs 19.8%(162/820), P =0.044; 29.1%(23/79) vs 19.8%(162/820), P =0.046]. The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups, which the most common ones were acinetobacter baumannii, pseudomonas aeruginosa and klebsiella pneumoniae. Conclusion: E-VAP and L-VAP have different risk factors, however related pathogens are similar. Different specific preventive strategies are suggested based on different onset of VAP.

  3. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…

  4. An admixture analysis of age of onset in agoraphobia.

    PubMed

    Tibi, Lee; van Oppen, Patricia; Aderka, Idan M; van Balkom, Anton J L M; Batelaan, Neeltje M; Spinhoven, Philip; Penninx, Brenda W; Anholt, Gideon E

    2015-07-15

    Age of onset is an important epidemiological indicator in characterizing disorders׳ subtypes according to demographic, clinical and psychosocial determinants. While investigated in various psychiatric conditions, age of onset and related characteristics in agoraphobia have yet to be examined. In light of the new diagnostic status in the DSM-5 edition of agoraphobia as independent from panic disorder, research on agoraphobia as a stand-alone disorder is needed. Admixture analysis was used to determine the best-fitting model for the observed ages at onset of 507 agoraphobia patients participating in the Netherlands Study of Depression and Anxiety (age range 18-65). Associations between agoraphobia age of onset and different demographic, clinical and psychosocial determinants were examined using multivariate logistic regression analysis. Admixture analyses identified two distributions of age of onset, with 27 as the cutoff age (≤27; early onset, >27; late onset). Early onset agoraphobia was only independently associated with family history of anxiety disorders (p<0.01) LIMITATIONS: Age of onset was assessed retrospectively, and analyses were based on cross-sectional data. The best distinguishing age of onset cutoff of agoraphobia was found to be 27. Early onset agoraphobia might constitute of a familial subtype. As opposed to other psychiatric disorders, early onset in agoraphobia does not indicate for increased clinical severity and/or disability. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations.

    PubMed

    Brunner, Patrick M; Israel, Ariel; Zhang, Ning; Leonard, Alexandra; Wen, Huei-Chi; Huynh, Thy; Tran, Gary; Lyon, Sarah; Rodriguez, Giselle; Immaneni, Supriya; Wagner, Annette; Zheng, Xiuzhong; Estrada, Yeriel D; Xu, Hui; Krueger, James G; Paller, Amy S; Guttman-Yassky, Emma

    2018-06-01

    Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (<5 years old) with early-onset AD (<6 months disease duration) compared with age-matched control subjects and adults with longstanding AD. Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored T H 2-centered inflammation, pediatric AD also showed significant T H 17/T H 22 skewing but lacked the T H 1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease. Copyright © 2018 American Academy of Allergy

  6. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    ERIC Educational Resources Information Center

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  7. The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

    PubMed

    Zhu, Jie; Yang, Peng; Liu, Xiang; Yan, Li; Rampersad, Sharvan; Li, Feng; Li, Hong; Sheng, Chunjun; Cheng, Xiaoyun; Zhang, Manna; Qu, Shen

    2017-08-01

    This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients. Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group. Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

  9. PP087. Multicenter external validation and recalibration of a model for preconceptional prediction of recurrent early-onset preeclampsia.

    PubMed

    van Kuijk, Sander; Delahaije, Denise; Dirksen, Carmen; Scheepers, Hubertina C J; Spaanderman, Marc; Ganzevoort, W; Duvekot, Hans; Oudijk, M A; van Pampus, M G; Dadelszen, Peter von; Peeters, Louis L; Smiths, Luc

    2013-04-01

    In an earlier paper we reported on the development of a model aimed at the prediction of preeclampsia recurrence, based on variables obtained before the next pregnancy (fasting glucose, BMI, previous birth of a small-for-gestational-age infant, duration of the previous pregnancy, and the presence of hypertension). To externally validate and recalibrate the prediction model for the risk of recurrence of early-onset preeclampsia. We collected data about course and outcome of the next ongoing pregnancy in 229 women with a history of early-onset preeclampsia. Recurrence was defined as preeclampsia requiring delivery before 34 weeks. We computed risk of recurrence and assessed model performance. In addition, we constructed a table comparing sensitivity, specificity, and predictive values for different suggested risk-thresholds. Early-onset preeclampsia recurred in 6.6% of women. The model systematically underestimated recurrence risk. The model's discriminative ability was modest, the area under the receiver operating characteristic curve was 58.9% (95% CI: 45.1 - 72.7). Using relevant risk-thresholds, the model created groups that were only moderately different in terms of their average risk of recurrent preeclampsia (Table 1). Compared to an AUC of 65% in the development cohort, the discriminate ability of the model was diminished. It had inadequate performance to classify women into clinically relevant risk groups. Copyright © 2013. Published by Elsevier B.V.

  10. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.

    PubMed

    Nemos, C; Lambert, L; Giuliano, F; Doray, B; Roubertie, A; Goldenberg, A; Delobel, B; Layet, V; N'guyen, M A; Saunier, A; Verneau, F; Jonveaux, P; Philippe, C

    2009-10-01

    The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.

  11. Is an Early Age at Illness Onset in Schizophrenia Associated With Increased Genetic Susceptibility? Analysis of Data From the Nationwide Danish Twin Register.

    PubMed

    Hilker, Rikke; Helenius, Dorte; Fagerlund, Birgitte; Skytthe, Axel; Christensen, Kaare; Werge, Thomas M; Nordentoft, Merete; Glenthøj, Birte

    2017-04-01

    Early age at illness onset has been viewed as an important liability marker for schizophrenia, which may be associated with an increased genetic vulnerability. A twin approach can be valuable, because it allows for the investigation of specific illness markers in individuals with a shared genetic background. We linked nationwide registers to identify a cohort of twin pairs born in Denmark from 1951 to 2000 (N=31,524 pairs), where one or both twins had a diagnosis in the schizophrenia spectrum. We defined two groups consisting of; N=788 twin pairs (affected with schizophrenia spectrum) and a subsample of N=448 (affected with schizophrenia). Survival analysis was applied to investigate the effect of age at illness onset. We found that early age at illness onset compared to later onset in the first diagnosed twin can be considered a major risk factor for developing schizophrenia in the second twin. Additionally, we found that the stronger genetic component in MZ twins compared to DZ twins is manifested in the proximity of assigned diagnosis within pairs. Early onset schizophrenia could be linked to a more severe genetic predisposition, indicating that age might be perceived as a clinical marker for genetic vulnerability for the illness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Sex-specific cognitive abnormalities in early-onset psychosis.

    PubMed

    Ruiz-Veguilla, Miguel; Moreno-Granados, Josefa; Salcedo-Marin, Maria D; Barrigon, Maria L; Blanco-Morales, Maria J; Igunza, Evelio; Cañabate, Anselmo; Garcia, Maria D; Guijarro, Teresa; Diaz-Atienza, Francisco; Ferrin, Maite

    2017-01-01

    Brain maturation differs depending on the area of the brain and sex. Girls show an earlier peak in maturation of the prefrontal cortex. Although differences between adult females and males with schizophrenia have been widely studied, there has been less research in girls and boys with psychosis. The purpose of this study was to examine differences in verbal and visual memory, verbal working memory, auditory attention, processing speed, and cognitive flexibility between boys and girls. We compared a group of 80 boys and girls with first-episode psychosis to a group of controls. We found interactions between group and sex in verbal working memory (p = 0.04) and auditory attention (p = 0.01). The female controls showed better working memory (p = 0.01) and auditory attention (p = 0.001) than males. However, we did not find any sex differences in working memory (p = 0.91) or auditory attention (p = 0.93) in the psychosis group. These results are consistent with the presence of sex-modulated cognitive profiles at first presentation of early-onset psychosis.

  13. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

    PubMed

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Late-onset offending: fact or fiction.

    PubMed

    Wiecko, Filip M

    2014-01-01

    This research focuses on a detailed exploration of late-onset offending. Using the National Youth Survey, this work seeks to answer three questions. First, is late-onset offending a real phenomenon? Second, if late onset does exist, is the evidence for it conditioned by how we define crime and delinquency? Finally, is late-onset offending an artifact of measurement methodology? Most literature evidencing late onset relies on official police contact and arrest data. Propensity or control theories in general posit that late onset should not exist. Propensity, namely self-control, should be instilled early in life and if absent, results in early initiation into crime and delinquency. Research in developmental psychology seems to support this notion. The findings from this study indicate that late-onset offending is almost nonexistent when self-reported measures are used leading one to conclude that contemporary evidence for late-onset is heavily conditioned by how we measure crime and delinquency. A comprehensive discussion includes future directions for research, and implications for theory development and methodology.

  15. Atmospheric 7Be Concentration Changes as a Possible New Indicator for Early Warning on Indian Monsoon Onset

    NASA Astrophysics Data System (ADS)

    Terzi, L.; Kalinowski, M.; Schoeppner, M.; kusmierczyk-michulec, J.

    2017-12-01

    With 80 radionuclide detector systems worldwide, the International Monitoring System (IMS) offers an unprecedented opportunity to use 7Be as an aerosol tracer for global atmospheric cell dynamics. Meteorological processes such as ENSO onset, ITCZ shift, location and progression of Hadley-Ferrel cell convergence zone (HFCZ) have been reconstructed using long term timeseries of ground based 7Be observations. Cross correlation of 7Be activity concentrations also demonstrated to serve as an early warning indicator for Indian monsoons showing a possible 30-day warning prior to monsoon onset (Terzi and Kalinowski, 2017). Here we present what role phenomena that we can observe with 7Be, namely ITCZ and HFCZ, play in monsoon formation and how the prediction of monsoon onset relates to ENSO prediction. Performance, lead time and reliability of 7Be as monsoon onset indicator are then compared to current meteorological indicators. Near surface 7Be activity concentrations may help address outstanding challenges in monsoon research by integrating a new perspective across disciplines.

  16. Exploring reasons for late identification of children with early-onset hearing loss.

    PubMed

    Fitzpatrick, Elizabeth M; Dos Santos, Johnny Cesconetto; Grandpierre, Viviane; Whittingham, JoAnne

    2017-09-01

    Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children. Population level data related to age of first assessment, age of identification and clinical characteristics were collected prospectively for all children identified through the UNHS program. We documented the number of children who experienced delay (defined as more than 3 months) from initial audiologic assessment to confirmation of hearing loss. A detailed chart review was subsequently performed to examine the reasons for delay to confirmation. Of 418 children identified from 2003 to 2013, 182 (43.5%) presented with congenital or early onset hearing loss, of whom 30 (16.5%) experienced more than 3 months delay from initial audiologic assessment to confirmation of their hearing disorder. The median age of first assessment and confirmation of hearing loss for these 30 children was 3.7 months (IQR: 2.0, 7.6) and 13.8 months (IQR: 9.7, 26.1) respectively. Close examination of the factors related to delay to confirmation revealed that for the overwhelming majority of children, a constellation of factors contributed to late diagnosis. Several children (n = 22; 73.3%) presented with developmental/medical issues, 15 of whom also had middle ear dysfunction at assessment, and 9 of whom had documented family follow-up concerns. For the remaining eight children, additional reasons included ongoing middle ear dysfunction for five children, complicated by family follow-up concerns (n = 3) and mild

  17. Canadian patient played key role in uncovering secrets about early-onset Alzheimer's disease.

    PubMed Central

    Lyttle, J

    1996-01-01

    Last June, the University of Toronto announced that Canadian scientists and a team of international researchers had discovered the gene responsible for most cases of early-onset Alzheimer's disease. One of the key players in that discovery had died just 3 months earlier. Frances Hodge, who participated in a battery of tests for the 20 years she lived with the disease, helped lead researchers to gene S182--and an ember of hope for future generations. Images p906-a PMID:8634971

  18. The Prevention of Early-Onset Neonatal Group B Streptococcal Disease.

    PubMed

    Money, Deborah; Allen, Victoria M

    2016-12-01

    To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are

  19. X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

    PubMed Central

    Shamim, Daniah; Alleyne, Karen

    2017-01-01

    Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

  20. X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

    PubMed

    Shamim, Daniah; Alleyne, Karen

    2017-01-01

    Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

  1. Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

    PubMed

    Kurz, Ella; Davis, Deborah

    2015-04-17

    Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

  2. Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

    PubMed Central

    Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

    2012-01-01

    Objective To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method Neurocognitive functioning of youth (ages 8–19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site randomized, double-blind clinical trial comparing molindone, olanzapine or risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Results Seventy-seven of 116 TEOSS participants (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Conclusions Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. PMID:22525956

  3. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

    PubMed

    Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

    2013-01-01

    There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

  4. Family socioeconomic position in early life and onset of depressive symptoms and depression: a prospective cohort study.

    PubMed

    Joinson, Carol; Kounali, Daphne; Lewis, Glyn

    2017-01-01

    To investigate whether low parental socioeconomic position (SEP) at birth is associated only with early-onset depressive symptoms in offspring. This prospective cohort study used data on 9193 individuals (4768 females, 4425 males) from the Avon Longitudinal Study of Parents and Children. Depressive symptoms during three age periods (10-12, 12-16, 16-20 years) were assessed using the Short Mood and Feelings Questionnaire, and ICD-10 depression at age 18 was assessed using the Clinical Interview Schedule-Revised. Low SEP was associated with increased incidence rates of depressive symptoms in all age periods, with indicators of low standard of living showing the strongest associations. For instance, incidence rate ratios for material hardship were 1.75 (95% CI [1.42-2.15]) at 10-12 years, 1.36 (1.16-1.61) at 12-16 years and 1.39 (1.21-1.59) at 16-20 years. Low SEP was also associated with increased odds of ICD-10 depression at 18 years, ranging from OR = 1.20 (95% CI [0.94-1.52]) for manual social class to 1.74 (1.35-2.24) for material hardship. There was no evidence that depressive symptoms can be "subtyped" by the age of onset, because the association with low SEP was evident for early- and later-onset symptoms. If socioeconomic inequalities in early life have long-term adverse impacts on mental health, policies addressing these inequalities could benefit the mental health of the population.

  5. Early onset and differential temporospatial expression of melanopsin isoforms in the developing chicken retina.

    PubMed

    Verra, Daniela M; Contín, Maria Ana; Hicks, David; Guido, Mario E

    2011-07-07

    Retinal ganglion cells (RGCs) expressing the photopigment melanopsin (Opn4) display intrinsic photosensitivity. In this study, the presence of nonvisual phototransduction cascade components in the developing chicken retina and primary RGCs cultures was investigated, focusing on the two Opn4 genes: the Xenopus (Opn4x) and the mammalian (Opn4m) orthologs. Retinas were dissected at different embryonic (E) and postnatal (P) days, and primary RGC cultures were obtained at E8 and kept for 1 hour to 5 days. Samples were processed for RT-PCR and immunochemistry. Embryonic retinas expressed the master eye gene Pax6, the prospective RGC specification gene Brn3, and components of the nonvisual phototransduction cascade, such as Opn4m and the G protein q (Gq) mRNAs at very early stages (E4-E5). By contrast, expression of photoreceptor cell markers (CRX, red-opsin, rhodopsin, and α-transducin) was observed from E7 to E12. Opn4m protein was visualized in the whole retina as early as E4 and remained elevated from E6 to the postnatal days, whereas Opn4x was weakly detected at E8 and highly expressed after E11. RGC cultures expressed Gq mRNA, as well as both Opn4 mRNAs and proteins. Opn4m was restricted exclusively to the GC layer at all ages, whereas Opn4x was limited to the forming GC layer and optic nerve at E8, but by E15, its expression was mostly in Prox1(+) horizontal cells. The early expression onset of nonvisual phototransduction molecules could confer premature photosensitivity to RGCs, while the appearance of Opn4x expression in horizontal cells suggests the identification of a novel type of photosensitive cell in birds.

  6. Early onset of industrial-era warming across the oceans and continents.

    PubMed

    Abram, Nerilie J; McGregor, Helen V; Tierney, Jessica E; Evans, Michael N; McKay, Nicholas P; Kaufman, Darrell S

    2016-08-25

    The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-ad 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.

  7. Early Formed Astrophysical Objects and Cosmological Antimatter

    NASA Astrophysics Data System (ADS)

    Dolgov, Alexander D.

    Astronomical observations of recent years show that the universe at high redshifts (about ten) is densely populated by early formed objects: bright galaxies, quasars, gamma-bursters, and it contains a lot of metals and dust. Such a rich variety of early formed objects have not been expected in the standard model of formation of astrophysical objects. There is serious tension between the standard theory and the observations. We describe the model which relaxes this tension and nicely fits the data. The model naturally leads to the creation of cosmologically significant antimatter which may be abundant even in the Galaxy. Phenomenological consequences of our scenario and the possibility of distant registration of antimatter are discussed.

  8. Early formed astrophysical objects and cosmological antimatter

    NASA Astrophysics Data System (ADS)

    Dolgov, Alexander D.

    2016-10-01

    Astronomical observations of recent years show that the universe at high redshifts (about ten) is densely populated by early formed objects: bright galaxies, quasars, gamma-bursters, and it contains a lot of metals and dust. Such a rich variety of early formed objects have not been expected in the standard model of formation of astrophysical objects. There is serious tension between the standard theory and the observations. We describe the model which relaxes this tension and nicely fits the data. The model naturally leads to the creation of cosmologically significant antimatter which may be abundant even in the Galaxy. Phenomenological consequences of our scenario and the possibility of distant registration of antimatter are discussed.

  9. Alcohol use in motion pictures and its relation with early-onset teen drinking.

    PubMed

    Sargent, James D; Wills, Thomas A; Stoolmiller, Mike; Gibson, Jennifer; Gibbons, Frederick X

    2006-01-01

    Little is known about the impact of viewing depictions of alcohol in entertainment media on adolescent drinking behavior. Our aims were to assess drinking in a sample of popular contemporary movies and to examine the association of movie alcohol exposure with early-onset drinking in an adolescent sample. We conducted a school-based cross-sectional survey (N=4655) with longitudinal follow-up of never-drinkers (N=2406) involving adolescents ages 10-14 years and recruited from 15 New Hampshire and Vermont schools. Screen depictions of alcohol use were timed for each of 601 popular contemporary movies. Each adolescent was asked if he/she had seen a unique list of 50 movie titles, randomly selected from the larger pool. Movie alcohol use was summed for movies the adolescent had seen, adjusted to reflect exposure to the larger pool and modeled as a continuous variable. Ninety-two percent of the movies in the sample depicted drinking; median screen time for movie alcohol use was 2.5 minutes (interquartile range [IQR]: 0.9-5.0 minutes). Median exposure to movie alcohol use from the 601 movies was 8.6 hours (IQR: 4.6-13.5 hours). Overall 23.1% of the cross-sectional sample had tried alcohol, and 14.8% of initial nondrinkers had tried alcohol at the follow-up assessment. We found statistical evidence to support a curvilinear association between higher exposure to movie alcohol use and increased risk of prevalent and incident alcohol use, with a statistically significant linear and quadratic effect, and suggesting a higher dose-effect relationship at lower movie alcohol exposure levels compared to higher levels. The linear and the quadratic associations remained strong and significant in cross-sectional and prospective models after controlling for sociodemographics (grade in school, school, gender, parent education), personality characteristics of the adolescent (sensation seeking, rebelliousness, self-esteem), school performance, parenting style, and smoking experimentation

  10. Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

    PubMed

    Kawai, Toshinao; Arai, Katsuhiro; Harayama, Shizuko; Nakazawa, Yumiko; Goto, Fumihiro; Maekawa, Takanobu; Tamura, Eiichiro; Uchiyama, Toru; Onodera, Masafumi

    2015-08-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC. Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records. Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation. Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

  11. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    PubMed

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. The Northern Ireland Early Onset Psychosis Study: Phenomenology and Co-Morbidity in the First 25 Cases

    ERIC Educational Resources Information Center

    Fulton, Karen; Short, Mary; Harvey-Smith, Diane; Rushe, Teresa M.; Mulholland, Ciaran

    2008-01-01

    Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study…

  13. Is adolescent-onset first-episode psychosis different from adult onset?

    PubMed

    Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-08-01

    To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated psychosis, diagnosis, length of prodromal period, premorbid adjustment, level of psychotic, negative, depressive, anxiety, and extrapyramidal symptoms, and alcohol and drug use. Eighty-two patients (40.8%) had an onset of psychosis during adolescence (ages 15-18) and 119 (59.2%) during young adulthood (ages 19-30). The adolescent-onset group experienced longer delays in treatment of psychosis (duration of untreated psychosis) (p < .02), showed modestly worse premorbid functioning during late adolescence (p < .05), and were more likely to present with bizarre behavior (p < .01) and primary negative symptoms (p < .01). Patients with adolescent onset of psychosis are more likely to present with clinical characteristics that portend a poorer outcome and may require a different approach to early identification and treatment.

  14. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

    PubMed

    Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-06-01

    To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease.

    PubMed

    Palmio, Johanna; Jonson, Per Harald; Evilä, Anni; Auranen, Mari; Straub, Volker; Bushby, Kate; Sarkozy, Anna; Kiuru-Enari, Sari; Sandell, Satu; Pihko, Helena; Hackman, Peter; Udd, Bjarne

    2015-11-01

    DNAJB6 is the causative gene for limb-girdle muscular dystrophy 1D (LGMD1D). Four different coding missense mutations, p.F89I, p.F93I, p.F93L, and p.P96R, have been reported in families from Europe, North America and Asia. The previously known mutations cause mainly adult-onset proximal muscle weakness with moderate progression and without respiratory involvement. A Finnish family and a British patient have been studied extensively due to a severe muscular dystrophy. The patients had childhood-onset LGMD, loss of ambulation in early adulthood and respiratory involvement; one patient died of respiratory failure aged 32. Two novel mutations, c.271T > A (p.F91I) and c.271T > C (p.F91L), in DNAJB6 were identified by whole exome sequencing as a cause of this severe form of LGMD1D. The results were confirmed by Sanger sequencing. The anti-aggregation effect of the mutant DNAJB6 was investigated in a filter-trap based system using transient transfection of mammalian cell lines and polyQ-huntingtin as a model for an aggregation-prone protein. Both novel mutant proteins show a significant loss of ability to prevent aggregation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined.more » After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had

  17. Admixture analysis of age of onset in generalized anxiety disorder.

    PubMed

    Rhebergen, Didi; Aderka, Idan M; van der Steenstraten, Ira M; van Balkom, Anton J L M; van Oppen, Patricia; Stek, Max L; Comijs, Hannie C; Batelaan, Neeltje M

    2017-08-01

    Age of onset is a marker of clinically relevant subtypes in various medical and psychiatric disorders. Past research has also reported that age of onset in generalized anxiety disorder (GAD) is clinically significant; but, in research to date, arbitrary cut-off ages have been used. In the present study, admixture analysis was used to determine the best fitting model for age of onset distribution in GAD. Data were derived from 459 adults with a diagnosis of GAD who took part in the Netherlands Study of Depression and Anxiety (NESDA). Associations between age of onset subtypes, identified by admixture analysis, and sociodemographic, clinical, and vulnerability factors were examined using univariate tests and multivariate logistic regression analyses. Two age of onset distributions were identified: an early-onset group (24 years of age and younger) and a late-onset group (greater than 24 years of age). Multivariate analysis revealed that early-onset GAD was associated with female gender (OR 2.1 (95%CI 1.4-3.2)), higher education (OR 1.1 (95%CI 1.0-1.2)), and higher neuroticism (OR 1.4 (95%CI 1.1-1.7)), while late-onset GAD was associated with physical illnesses (OR 1.3 (95%CI 1.1-1.7)). Study limitations include the possibility of recall bias given that age of onset was assessed retrospectively, and an inability to detect a possible very-late-onset GAD subtype. Collectively, the results of the study indicate that GAD is characterized by a bimodal age of onset distribution with an objectively determined early cut-off at 24 years of age. Early-onset GAD is associated with unique factors that may contribute to its aetiology; but, it does not constitute a more severe subtype compared to late-onset GAD. Future research should use 24 years of age as the cut-off for early-onset GAD to when examining the clinical relevance of age of onset for treatment efficacy and illness course. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Intrapartum antibiotics and early onset neonatal sepsis caused by group B Streptococcus and by other organisms in Australia. Australasian Study Group for Neonatal Infections.

    PubMed

    Isaacs, D; Royle, J A

    1999-06-01

    Early onset group B streptococcal (EOGBS) infection, the major neonatal infection in industrialized countries, can be prevented by intrapartum antibiotics, but population studies are lacking. This study aimed to determine the incidence of early onset infections caused by group B Streptococcus (GBS) and other organisms in Australia and to assess intrapartum antibiotic use. Longitudinal, prospective surveillance of neonatal infections in Australian neonatal units from 1991 to 1997. Early onset infection defined as clinical sepsis in first 48 h after birth, with positive cultures of blood or cerebrospinal fluid or positive urine GBS antigen detection. The incidence of EOGBS sepsis fell from 2.0 per 1000 live births (95% confidence interval, 1.4, 2.5) in 1991 to 1993, to 1.3 (1.2, 1.4) in 1993 to 1995, to 0.5 (0.4, 0.7) in 1995 to 1997 (P < 0.0001). The incidence in Aboriginal babies was 5.2 (1.8, 8.6) in 1991 to 1993, 5.1 (3.0, 7.2) in 1993 to 1995 and 1.8 (1.1, 2.5) in 1995 to 1997 (P < 0.05). The incidence of early onset infections caused by organisms other than GBS also fell, from 1.2 per 1000 live births (0.8, 1.7) in 1991 to 1993, to 0.8 (0.7, 0.9) in 1993 to 1995 and 0.5 (0.3, 0.7) in 1995 to 1997 (P < 0.0001). In 1991, 3 of 9 study hospitals had a formal policy on intrapartum antibiotic use, whereas in 1997 all 11 hospitals had a formal policy (P=0.002). A steady fall in EOGBS infections in Australia from 1991 to 1997 has been associated with increasing use of intrapartum antibiotics. Increased antibiotic use is probably causal in the fall in GBS, because the incidence of early onset infections caused by other organisms has also fallen.

  19. Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study.

    PubMed

    Corrado, Bruno; Sommella, Nadia; Ciardi, Gianluca; Raiano, Enza; Scala, Iris; Strisciuglio, Pietro; Servodio Iammarrone, Clemente

    2018-02-19

    The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognityive skills. The study objectives were (a) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome, (b) to examine differences in walking onset by patient characteristics, (c) to verify the effect of early physical therapy (Neurodevelopmental Treatment on the basis of Bobath Concept practised within the first months of life) in the achievement of that skill. A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorobities and rehabilitation practised since birth were the eligibility criteria. The average age at which walking began in the sample was 26 months (Standard Deviation = 9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practised, early physical therapy was able to contrast the delay in walking. NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influences positively the development of the following motor and cognitive skills.

  20. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    ERIC Educational Resources Information Center

    McNamara, Robert S.; Swaim, Randall C.; Rosen, Lee A.

    2010-01-01

    This study examines the moderating effects of negative affect on the relationship between early drinking onset and binge-drinking behavior. Six hundred and thirty-five eleventh- and twelfth-grade students completed the American Drug and Alcohol Survey and reported on a variety of measures, including items assessing anxiety, anger, depression, age…

  1. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

  2. Incidence of early-onset dementia in Mar del Plata.

    PubMed

    Sanchez Abraham, M; Scharovsky, D; Romano, L M; Ayala, M; Aleman, A; Sottano, E; Etchepareborda, I; Colla Machado, C; García, M I; Gonorazky, S E

    2015-03-01

    Early-onset dementia (EOD) is defined as dementia with onset before the age of 65 years. EOD is increasingly recognised as an important clinical and social problem with devastating consequences for patients and caregivers. Determine the annual crude incidence rate and the specific incidence rates by sex and age in patients with EOD, and the standardised rate using the last national census of the population of Argentina (NCPA), from 2010. Hospital Privado de Comunidad, Mar del Plata, Argentina, attends a closed population and is the sole healthcare provider for 17 614 people. Using the database pertaining to the Geriatric Care department, we identified all patients diagnosed with EOD between 1 January, 2005 and 31 December, 2011. EOD was defined as dementia diagnosed in patients younger than 65. The study period yielded 14 patients diagnosed with EOD out of a total of 287 patients evaluated for memory concerns. The crude annual incidence of EOD was 11 per 100 000/year (CI 95%: 6.25-19.1): 17 per 100 000 (CI 95%: 7.2-33.1) in men and 8 per 100 000 (CI 95%: 3.4-17.2) in women. We observed a statistically significant increase when comparing incidence rates between patients aged 21 to <55 years and ≥ 55 to <65 years (3 vs 22 per 100 000, P=.0014). The rate adjusted by NCPA census data was 5.8 cases of EOD habitants/year. This study, conducted in a closed population, yielded an EOD incidence rate of 11 per 100 000 inhabitants/year. To the best of our knowledge, this is the first prospective epidemiological study in Argentina and in Latin America. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  3. Epileptic spasms and early-onset photosensitive epilepsy in Patau syndrome: An EEG study.

    PubMed

    Spagnoli, Carlotta; Kugathasan, Umaiyal; Brittain, Helen; Boyd, Stewart G

    2015-08-01

    Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  4. Rapid onset of efficacy of rasagiline in early Parkinson's disease.

    PubMed

    Zambito Marsala, Sandro; Vitaliani, Roberta; Volpe, Daniele; Capozzoli, Francesca; Baroni, Luciana; Belgrado, Enrico; Borsato, Carlo; Gioulis, Manuela; Marchini, Corrado; Antonini, Angelo

    2013-11-01

    Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson's disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson's Disease Rating Scale (UPDRSIII) and the Hoehn-Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (-6.7 at week 1 and -8.9 at week 4) and single items, as well as mean HY score (-0.40 at week 1 and -0.67 at week 4), significantly decreased from baseline (p < 0.001). Improvements were significant in both therapy-naive and add-on therapy patients: the mean decreases from baseline to week 4 in UPDRSIII and HY score were -8.8 and -0.46, and -9.0 and -0.74, respectively, in the two subgroups. The mean decrease from baseline in UPDRSIII and HY score did not significantly differ in patients aged > or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.

  5. Early and Late Onset Side Effects of Photodynamic Therapy

    PubMed Central

    Borgia, Francesco; Giuffrida, Roberta; Caradonna, Emanuela; Guarneri, Fabrizio; Cannavò, Serafinella P.

    2018-01-01

    Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. PMID:29382133

  6. Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

    PubMed

    Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

    2015-01-01

    Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

  7. Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

    PubMed

    Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

    2018-01-01

    Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

  8. High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    AWARD NUMBER: W81XWH-13-1-0371 TITLE: High-Throughput Sequencing of Germline and Tumor From Men with Early- Onset Metastatic Prostate Cancer...DATES COVERED 30 Sep 2013 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER High-Throughput Sequencing of Germline and Tumor From Men with...presenting with metastatic prostate cancer at a young age (before age 60 years). Whole exome sequencing identified a panel of germline variants that have

  9. Treating Children with Early-Onset Conduct Problems and Callous-Unemotional Traits: An Empirical Evaluation of KooLKIDS

    ERIC Educational Resources Information Center

    Houghton, Stephen; Carroll, Annemaree; Zadow, Corinne; O'connor, Emma Sanders; Hattie, John; Lynn, Sasha

    2017-01-01

    Children with early-onset conduct problems (EOCP) and callous-unemotional (CU) traits are highly resistant to treatment and cost society significantly more than their healthy counterparts. Employing a multiple baseline design, 13 males (9.0-10.2 years of age) with a history of school suspensions were sequentially introduced to KooLKIDS, a…

  10. Melancholia in later life: late and early onset differences in presentation, course, and dementia risk.

    PubMed

    Sachs-Ericsson, Natalie; Moxley, Jerad H; Corsentino, Elizabeth; Rushing, Nicole Collins; Sheffler, Julia; Selby, Edward A; Gotlib, Ian; Steffens, David C

    2014-09-01

    Depression is a risk factor for cognitive decline and dementia. This risk may vary with age of onset and depression subtype. Late onset depression (LOD, 60 years and older) is associated with more cognitive decline, whereas early onset depression (EOD, before 60 years) is associated with more residual depressive symptoms. Potential differences may reflect divergent etiologies. These onset differences, however, have not been examined in the melancholic subtype of depression in older adults. Data were obtained from the Neurocognitive Outcomes of Depression in the Elderly study. Participants (N = 284, 73% EOD-melancholic (EOD-M) and 27% LOD-melancholic (LOD-M)) were followed up over 3 years. Factor analyses examined differences in baseline depressive symptoms. Hierarchical linear growth curve models examined changes in depressive symptoms (Montgomery-Asberg Depression Rating Scale) and cognition (mini mental state examination). An annual clinical review panel assigned diagnoses of dementia. The LOD-M participants had more vegetative symptoms at baseline. LOD-M exhibited greater cognitive decline but fewer residual depressive symptoms than EOD-M. Among participants who remained in the study for at least 1 year, in uncontrolled analyses, a greater percentage of LOD-M compared with EOD-M developed dementia (23.0% vs. 7.8%). Whereas in logistic analyses, controlling for baseline demographics, age at onset remained a predictor of dementia, the odds ratio suggested that the effect was relatively small. The EOD-M and LOD-M participants have a different presentation and course. LOD-M may represent a syndrome of neuropsychiatric deterioration with expression of both depressive symptoms and cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Protocol for systematic review of evidence on the determinants and influence of early glycaemic control in childhood-onset type 1 diabetes.

    PubMed

    Mazarello Paes, Veena; Charalampopoulos, Dimitrios; Khanolkar, Amal R; Taylor-Robinson, David; Viner, Russell; Edge, Julie; Stephenson, Terence; Amin, Rakesh

    2015-11-12

    Landmark studies in adult-onset type 1 diabetes (T1D) populations indicate that improved glycaemic control through use of intensive insulin therapy is strongly associated with reduced risk for the development of diabetes-related complications and mortality in later years. However, it is unclear whether these associations can be extrapolated to childhood-onset T1D, given the influence of other important biological and psychosocial determinants of glycaemic control, particularly during adolescence. The aims of the review are (1) to investigate the impact of early glycaemic control (within the first 2 years after diagnosis) on subsequent glycaemic trends and risk of complications during the life course of childhood-onset T1D and (2) to identify the predictors of early glycaemic control in children and young people (0-25 years). The methods used in this study are systematic identification, review and mapping of quantitative (intervention and observational) and qualitative literature; assessing the effect and predictors of early glycaemic control in T1D (diagnosed ≤18 years) on risk or prevalence of later complications. An iterated search strategy, with no language or period restrictions, was applied to identify studies from six electronic databases. This will be supplemented by hand-searching (reference lists and contacting authors of studies meeting the inclusion criteria). Studies assessing glycaemic control within the first 2 years of diagnosis in children (at baseline) will be quality-assessed against predefined criteria and mapped descriptively to future health outcomes. Extracted data will be analysed and synthesised using narrative and forest plots or harvest plots for quantitative evidence and thematic analyses for qualitative studies. To get a deeper understanding of the predictors of early glycaemic control in reducing complications in childhood and adult life, we will integrate qualitative and quantitative evidence using mixed methods or parallel synthesis

  12. Early-Onset Basal Cell Carcinoma and Indoor Tanning: A Population-Based Study

    PubMed Central

    Zens, M. Scot; Li, Zhigang; Stukel, Therese A.; Perry, Ann E.; Gilbert-Diamond, Diane; Sayarath, Vicki; Stephenson, Rita S.; Barton, Dorothea; Nelson, Heather H.; Spencer, Steven K.

    2014-01-01

    OBJECTIVE: Indoor tanning with UV radiation–emitting lamps is common among adolescents and young adults. Rising incidence rates of basal cell carcinoma (BCC) have been reported for the United States and elsewhere, particularly among those diagnosed at younger ages. Recent epidemiologic studies have raised concerns that indoor tanning may be contributing to early occurrence of BCC, and younger people may be especially vulnerable to cancer risk associated with this exposure. Therefore, we sought to address these issues in a population-based case–control study from New Hampshire. METHODS: Data on indoor tanning were obtained on 657 cases of BCC and 452 controls ≤50 years of age. RESULTS: Early-onset BCC was related to indoor tanning, with an adjusted odds ratio (OR) of 1.6 (95% confidence interval, 1.3–2.1). The strongest association was observed for first exposure as an adolescent or young adult, with a 10% increase in the OR with each age younger at first exposure (OR per year of age ≤23 = 1.1; 95% confidence interval, 1.0–1.2). Associations were present for each type of device examined (ie, sunlamps, tanning beds, and tanning booths). CONCLUSIONS: Our findings suggest early exposure to indoor tanning increases the risk of early development of BCC. They also underscore the importance of counseling adolescents and young adults about the risks of indoor tanning and for discouraging parents from consenting minors to this practice. PMID:24958589

  13. Early-onset basal cell carcinoma and indoor tanning: a population-based study.

    PubMed

    Karagas, Margaret R; Zens, M Scot; Li, Zhigang; Stukel, Therese A; Perry, Ann E; Gilbert-Diamond, Diane; Sayarath, Vicki; Stephenson, Rita S; Barton, Dorothea; Nelson, Heather H; Spencer, Steven K

    2014-07-01

    Indoor tanning with UV radiation-emitting lamps is common among adolescents and young adults. Rising incidence rates of basal cell carcinoma (BCC) have been reported for the United States and elsewhere, particularly among those diagnosed at younger ages. Recent epidemiologic studies have raised concerns that indoor tanning may be contributing to early occurrence of BCC, and younger people may be especially vulnerable to cancer risk associated with this exposure. Therefore, we sought to address these issues in a population-based case-control study from New Hampshire. Data on indoor tanning were obtained on 657 cases of BCC and 452 controls ≤50 years of age. Early-onset BCC was related to indoor tanning, with an adjusted odds ratio (OR) of 1.6 (95% confidence interval, 1.3-2.1). The strongest association was observed for first exposure as an adolescent or young adult, with a 10% increase in the OR with each age younger at first exposure (OR per year of age ≤23 = 1.1; 95% confidence interval, 1.0-1.2). Associations were present for each type of device examined (ie, sunlamps, tanning beds, and tanning booths). Our findings suggest early exposure to indoor tanning increases the risk of early development of BCC. They also underscore the importance of counseling adolescents and young adults about the risks of indoor tanning and for discouraging parents from consenting minors to this practice. Copyright © 2014 by the American Academy of Pediatrics.

  14. Clinical dissection of early onset absence epilepsy in children and prognostic implications.

    PubMed

    Agostinelli, Sergio; Accorsi, Patrizia; Beccaria, Francesca; Belcastro, Vincenzo; Canevini, Maria Paola; Capovilla, Giuseppe; Cappanera, Silvia; Dalla Bernardina, Bernardo; Darra, Francesca; Del Gaudio, Luigi; Elia, Maurizio; Falsaperla, Raffaele; Giordano, Lucio; Gobbi, Giuseppe; Minetti, Carlo; Nicita, Francesco; Parisi, Pasquale; Pavone, Piero; Pezzella, Marianna; Sesta, Michela; Spalice, Alberto; Striano, Salvatore; Tozzi, Elisabetta; Traverso, Monica; Vari, Stella; Vignoli, Aglaia; Zamponi, Nelia; Zara, Federico; Striano, Pasquale; Verrotti, Alberto

    2013-10-01

    To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  15. Focused Molding Using Adhesive Pads in Mehta Casting for Early-Onset Scoliosis.

    PubMed

    Abraham, Roby; Sponseller, Paul D

    2014-11-01

    Prospective clinical series. To determine the effect of adhesive pads placed over the apex of scoliosis curves on curve correction 1) after the first cast and 2) after the final cast. Early-onset scoliosis is often effectively managed by serial casting. Properly localizing the apex of the molds with the cast in place is challenging. The authors explored the effectiveness of a novel technique: incorporation of adhesive pads placed over the major curve apex before Mehta casting. The 27 patients who received body casts (2000-2013) were divided into 2 groups: those without and with apical adhesive pads (5-6 layers of pads placed on the major curve's apex during casting): non-pad (NP) group (n = 12) and pad (P) group (n = 15), respectively. Groups were compared regarding the percentage of Cobb angle change from the first cast and curve correction to a Cobb angle of <25° with Student t and chi-square tests (significance was p < .05). The mean percentage of major first-cast curve correction was 39% ± 18% and 56% ± 17% in the NP and P groups, respectively. Of the 26 patients out of a cast, 11 (42%) had a Cobb angle of <25°: 3 (25%) and 8 (57%) in the NP and P groups, respectively. The mean differences between the 2 groups in percentage of major curve correction and this Cobb angle correction were significant: p = .023 and .005, respectively. Adhesive pads placed over major curve(s) during Mehta casting were effective in increasing the amount of major curve correction from the first cast for idiopathic early-onset scoliosis and in decreasing curves to <25° at final follow-up. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  16. Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.

    PubMed

    Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran

    2010-03-01

    Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (<3%) of TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Elucidating Pathogenic Mechanisms of Early-onset Alzheimer's Disease in Down Syndrome Patients.

    PubMed

    Asai, Masashi; Kawakubo, Takashi; Mori, Ryotaro; Iwata, Nobuhisa

    2017-01-01

    Down syndrome (DS) patients demonstrate the neuropathology of Alzheimer's disease (AD) characterized by the formation of senile plaques and neurofibrillary tangles by age 40-50 years. It has been considered for a number of years that 1.5-fold expression of the gene for the amyloid precursor protein (APP) located on chromosome 21 leading to overproduction of amyloid-β peptide (Aβ) results in the early onset of AD in adults with DS. However, the mean age of onset of familial AD with the Swedish mutation on APP which has high affinity for β-secretase associated with a dramatic increase in Aβ production is about 55 years. This paradox indicates that there is a poor correlation between average ages of AD onset and the theoretical amount of Aβ production and that there are factors exacerbating AD on chromosome 21. We therefore focused on dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), since overexpressing transgenic mice show AD-like brain pathology. The overexpression of DYRK1A caused suppression of the activity of neprilysin (NEP), which is a major Aβ-degrading enzyme in the brain, and phosphorylation at the NEP cytoplasmic domain. NEP activity was markedly reduced in fibroblasts derived from DS patients compared with that in fibroblasts derived from healthy controls. This impaired activity of NEP was rescued by DYRK1A inhibition. These results show that DYRK1A overexpression causes suppression of NEP activity through its phosphorylation in DS patients. Our results suggest that DYRK1A inhibitors could be effective against AD not only in adults with DS but also in sporadic AD patients.

  18. Forming Disk Galaxies Early in the Universe

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-08-01

    What were galaxies like in the first 500 million years of the universe? According to simulations by Yu Feng (UC Berkeley) and collaborators, the earliest massive galaxies to form were mostly disk-shaped, rather than the compact clumps previously predicted. Early-Galaxy Models. Current models for galaxy formation predict that small perturbations in the distribution of matter in the early universe collapsed to form very compact, irregular, clumpy first galaxies. Observations support this: the furthest out that we've spotted disk-shaped galaxies is at z=3, whereas the galaxies we've observed from earlier times -- up to redshifts of z=8-10 -- are very compact. But could this be a selection effect, arising from the rarity of large galaxies in the early universe? Current surveys at high redshift have thus far only covered relatively small volumes of space, so it's not necessarily surprising that we haven't yet spotted any large disk galaxies. Similarly, numerical simulations of galaxy formation are limited in the size of the volume they can evolve, so resulting models of early galaxy formation also tend to favor compact clumpy galaxies over large disks. An Enormous Simulation. Pushing at these limitations, Feng and his collaborators used the Blue Waters supercomputer to carry out an enormous cosmological hydrodynamic simulation called BlueTides. In this simulation, they track 700 billion particles as they evolve in a volume of 400 comoving Mpc/h -- 40 times the volume of the largest previous simulation and 300 times the volume of the largest observational survey at these redshifts. What they find is that by z=8, a whopping 70% of the most massive galaxies (over 7 billion solar masses each) were disk-shaped, though they are more compact, gas-rich, and turbulent than present-day disk galaxies like the Milky Way. The way the most massive galaxies formed in the simulation also wasn't expected: rather than resulting from major mergers, they were built from smooth accretion

  19. Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy.

    PubMed

    Kimura, Nobusuke; Takahashi, Yukitoshi; Shigematsu, Hideo; Imai, Katsumi; Ikeda, Hiroko; Ootani, Hideyuki; Takayama, Rumiko; Mogami, Yukiko; Kimura, Noriko; Baba, Koichi; Matsuda, Kazumi; Tottori, Takayasu; Usui, Naotaka; Inoue, Yushi

    2014-12-01

    The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engel's class I (7.5±3.8) was higher than patients with Engel's class II-IV (2.6±3.4) (unpaired t-test with Welch's correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ≥70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively

  20. Chromosome 14 and late-onset familial alzheimer disease (FAD)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schellenberg, G.D.; Anderson, L.; Nemens, E.

    1993-09-01

    Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analysis were used, in 49 families with a mean age at onset [>=]60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependentmore » penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score [>=]2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P<.02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset [>=]60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 37 refs., 1 fig., 6 tabs.« less

  1. Ultrasound control of magnet growing rod distraction in early onset scoliosis.

    PubMed

    Pérez Cervera, T; Lirola Criado, J F; Farrington Rueda, D M

    2016-01-01

    The growing rod technique is currently one of the most common procedures used in the management of early onset scoliosis. However, in order to preserve spine growth and control the deformity it requires frequent surgeries to distract the rods. Magnetically driven growing rods have recently been introduced with same treatment goal, but without the inconvenience of repeated surgical distractions. One of the limitations of this technical advance is an increase in radiation exposure due to the increase in distraction frequency compared to conventional growing rods. An improvement of the original technique is presented, proposing a solution to the inconvenience of multiple radiation exposure using ultrasound technology to control the distraction process of magnetically driven growing rods. Copyright © 2014 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures.

    PubMed

    Bodian, Dale L; Schreiber, John M; Vilboux, Thierry; Khromykh, Alina; Hauser, Natalie S

    2018-06-01

    Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which clinical genetic testing yields causative mutations in ∼20%-50% of affected individuals. We report the case of a boy presenting with intractable seizures at 2 wk of age, for whom gene panel testing was unrevealing. Research-based whole-genome sequencing of the proband and four unaffected family members identified a de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple alternative transcripts, and the mutation lies in an exon in the brain-expressed forms. The mutation was undetected by gene panel sequencing because of its intronic location in the CDKL5 transcript typically used to define the exons of this gene for clinical exon-based tests (NM_003159). This is the first report of a patient with a mutation in an alternative transcript of CDKL5 This finding suggests that incorporating alternative transcripts into the design and variant interpretation of exon-based tests, including gene panel and exome sequencing, could improve the diagnostic yield. © 2018 Bodian et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures

    PubMed Central

    Bodian, Dale L.; Schreiber, John M.; Vilboux, Thierry; Khromykh, Alina; Hauser, Natalie S.

    2018-01-01

    Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which clinical genetic testing yields causative mutations in ∼20%–50% of affected individuals. We report the case of a boy presenting with intractable seizures at 2 wk of age, for whom gene panel testing was unrevealing. Research-based whole-genome sequencing of the proband and four unaffected family members identified a de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple alternative transcripts, and the mutation lies in an exon in the brain-expressed forms. The mutation was undetected by gene panel sequencing because of its intronic location in the CDKL5 transcript typically used to define the exons of this gene for clinical exon-based tests (NM_003159). This is the first report of a patient with a mutation in an alternative transcript of CDKL5. This finding suggests that incorporating alternative transcripts into the design and variant interpretation of exon-based tests, including gene panel and exome sequencing, could improve the diagnostic yield. PMID:29444904

  4. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

    PubMed

    Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS.

  5. The angiotensin converting enzyme D allele is an independent risk factor for early onset coronary artery disease.

    PubMed

    Vaisi-Raygani, Asad; Ghaneialvar, Hori; Rahimi, Zohreh; Nomani, Hamid; Saidi, Mohmadreza; Bahrehmand, Fariborz; Vaisi-Raygani, Aliakbar; Tavilani, Haidar; Pourmotabbed, Tayebeh

    2010-10-01

    The role of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in early onset coronary artery disease age < 55years (ECAD) is controversial. The aim of this study was to further evaluate the role of this ACE(I/D) gene polymorphism on the risk of premature CAD in patients from western Iran. The ACE(I/D) genotypes were detected by PCR-RFLP in 323 individuals undergoing their first coronary angiography. Patients were placed into two groups: ECAD and late onset CAD age ≥ 55years (LCAD). We found a statistically significant association of the ACE D allele, as homozygous or ACE ID plus DD genotypes (ID+DD), only in the ECAD subjects OR=1.35, p=0.015, OR=3.27, p=0.014, and OR=2.8, p=0.013, respectively. In addition, there was a significant association after adjustment for the absence of history of diabetes, presence of normolipidemia and absence of history of blood pressure [OR 1.38, p=0.017 and 2.35, p=0.02]. Our results indicated that the ACE D allele is a risk factor for early onset of CAD even after correcting for conventional risk factors. The incidence of triple vessel disease was significantly higher in individuals carrying ACE(D/D) genotype in ECAD patients compared to those who carried ACE(I/I) genotype (OR 3.38; p=0.019; 57.5% vs. 42.5%; p=0.013). The presence of D allele of ACE can be important independent risk factor in the onset of CAD patients less than 55 years old in a west population of Iran. Larger collaborative studies are needed to confirm these results. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Differentiation of neuropsychological features between posterior cortical atrophy and early onset Alzheimer's disease.

    PubMed

    Li, Jieying; Wu, Liyong; Tang, Yi; Zhou, Aihong; Wang, Fen; Xing, Yi; Jia, Jianping

    2018-05-10

    Posterior cortical atrophy (PCA) is a group of clinical syndromes characterized by visuospatial and visuoperceptual impairment, with memory relatively preserved. Although PCA is pathologically almost identical to Alzheimer's disease (AD), they have different cognitive features. Those differences have only rarely been reported in any Chinese population. The purpose of the study is to establish neuropsychological tests that distinguish the clinical features of PCA from early onset AD (EOAD). Twenty-one PCA patients, 20 EOAD patients, and 20 healthy controls participated in this study. Patients had disease duration of ≤4 years. All participants completed a series of neuropsychological tests to evaluate their visuospatial, visuoperceptual, visuo-constructive, language, executive function, memory, calculation, writing, and reading abilities. The cognitive features of PCA and EOAD were compared. All the neuropsychological test scores showed that both the PCA and EOAD patients were significantly more impaired than people in the control group. However, PCA patients were significantly more impaired than EOAD patients in visuospatial, visuoperceptual, and visuo-constructive function, as well as in handwriting, and reading Chinese characters. The profile of neuropsychological test results highlights cognitive features that differ between PCA and EOAD. One surprising result is that the two syndromes could be distinguished by patients' ability to read and write Chinese characters. Tests based on these characteristics could therefore form a brief PCA neuropsychological examination that would improve the diagnosis of PCA.

  7. Completed suicide in an autopsy-confirmed case of early onset Alzheimer's disease.

    PubMed

    Hartzell, Jennifer Wiener; Geary, Richard; Gyure, Kymberly; Chivukula, Venkata Ravi; Haut, Marc W

    2018-04-01

    We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer's disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer's disease. In particular, our patient's death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it. The case is discussed in the context of literature differentiating the neural circuitry propagating impulsive versus planned suicidal acts.

  8. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  9. Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study

    PubMed Central

    2014-01-01

    Introduction Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease. Methods In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years). Results LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher

  10. Psychometric Validation of the Traditional Chinese Version of the Early Onset Scoliosis-24 Item Questionnaire (EOSQ-24).

    PubMed

    Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Wong, Carlos King Ho; Samartzis, Dino; Luk, Keith Dip-Kei; Lam, Cindy Lo Kuen; Cheung, Kenneth Man Chee

    2016-12-15

    Questionnaire translation and validation. The aim of this study was to translate and cross-culturally adapt the Early Onset Scoliosis-24 item Questionnaire (EOSQ-24) into traditional Chinese, and to assess its validity, reliability, and sensitivity in Southern-Chinese patients diagnosed with early onset scoliosis (EOS). Relying on radiographs alone for assessing treatment outcomes in EOS patients is inadequate. To properly gauge health-related quality of life, a disease-specific instrument that assesses patient quality of life and the burden of primary caregivers is necessary. The EOSQ-24 was created for this purpose, but it has not been adapted to the Chinese language. The translation and cross-cultural adaptation of the original English EOSQ-24 were performed using the method of double forward and single backward translations, followed by a panel review. EOS patients of Southern-Chinese descent were recruited, via convenience sampling from a scoliosis specialty clinic. These patients' parents/caretakers were then administered the traditional Chinese EOSQ-24, Likert Scale regarding the understanding of completed EOSQ-24, and the Child Health Questionnaire Parent Form 50 (CHQ-PF50) (Traditional Chinese). Reliability was analyzed using Cronbach alpha. Construct validity of domains and subdomains was assessed using Spearman correlation test against CHQ-PF50 domains with similar constructs. Sensitivity of the EOSQ-24 scores was determined by performing known group comparisons. A total of 100 EOS patients were recruited. A very good reliability was demonstrated (Cronbach α: 0.896) and internal consistency of all domains was excellent (Cronbach α: 0.829-0.919). Subdomain scores of EOSQ-24 and CHQ-PF50 had significant correlations (P < 0.001), indicating a good construct validity. This is the first psychometric study to translate and adapt the EOSQ-24 questionnaire for Chinese EOS patients and it has been found to have satisfactory validity, reliability, and

  11. Age of onset group characteristics in forensic patients with schizophrenia.

    PubMed

    Vinokur, D; Levine, S Z; Roe, D; Krivoy, A; Fischel, T

    2014-03-01

    This study aims to empirically identify age of onset groups and their clinical and background characteristics in forensic patients with schizophrenia. Hospital charts were reviewed of all 138 forensic patients with schizophrenia admitted to Geha Psychiatric Hospital that serves a catchment area of approximately 500,000 people, from 2000 to 2009 inclusive. Admixture analysis empirically identified early- (M=19.99, SD=3.31) and late-onset groups (M=36.13, SD=9.25). Early-onset was associated with more suicide attempts, violence before the age of 15, and early conduct problems, whereas late-onset was associated with a greater likelihood of violence after the age of 18 and marriage (P<0.01). The current findings provide clinicians with a unique direction for risk assessment and indicate differences in violence between early- and late-onset schizophrenia, particularly co-occurrence of harmful behavioral phenotypes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  12. Do spouse caregivers of persons with early- and late-onset dementia cope differently? A comparative study.

    PubMed

    Wawrziczny, Emilie; Pasquier, Florence; Ducharme, Francine; Kergoat, Marie-Jeanne; Antoine, Pascal

    To explore spouse caregivers' means of coping with the disease and compare them based on the age of onset of the disease in order to adapt support programs. Interviews were conducted with 38 spouse caregivers of persons with late-onset dementia (PLOD) and 40 spouse caregivers of persons with early onset dementia (PEOD). The first step in the analysis was qualitative, using QSR N'Vivo 10 to identify the coping strategies. The second step was quantitative, comparing the coping strategies based on the age of onset of the disease with a χ2 test. An inventory of 26 strategies used by all caregivers was established and consolidated into two groups: acceptance strategies and avoidance strategies. The statistical results show that some strategies were used by the two groups of caregivers. However, when differences emerged, the "Planning" strategy was used by spouse caregivers of PEOD, whereas the "Re-arranging", "Humor" and "Getting away from the entourage" strategies were used by spouse caregivers of PLOD. It would be interesting to develop a support program with a common framework and specific modules depending on the age of onset of the disease. Common modules would permit developing and strengthening acceptance strategies. Specific modules for caregivers of PEOD would guide them in the acquisition of more adaptability and flexibility in the assistance provided to the PWD, which can sometimes be too rigid and controlled. Specific modules for caregivers of PLOD would help them to develop the ability to request help and identify the intervention limits of the entourage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Meteorite Dichotomy Implies that Jupiter Formed Early

    NASA Astrophysics Data System (ADS)

    Kruijer, T. S.; Burkhardt, C.; Budde, G.; Kleine, T.

    2018-05-01

    Meteorites derive from two distinct nebular reservoirs that co-existed and remained spatially separated between 1 and 3–4 Ma after CAIs. This can most easily be explained if Jupiter acted as a barrier and formed early, within less than 1 Ma.

  14. Comparison of Passive Microwave-Derived Early Melt Onset Records on Arctic Sea Ice

    NASA Technical Reports Server (NTRS)

    Bliss, Angela C.; Miller, Jeffrey A.; Meier, Walter N.

    2017-01-01

    Two long records of melt onset (MO) on Arctic sea ice from passive microwave brightness temperatures (Tbs) obtained by a series of satellite-borne instruments are compared. The Passive Microwave (PMW) method and Advanced Horizontal Range Algorithm (AHRA) detect the increase in emissivity that occurs when liquid water develops around snow grains at the onset of early melting on sea ice. The timing of MO on Arctic sea ice influences the amount of solar radiation absorbed by the ice-ocean system throughout the melt season by reducing surface albedos in the early spring. This work presents a thorough comparison of these two methods for the time series of MO dates from 1979through 2012. The methods are first compared using the published data as a baseline comparison of the publically available data products. A second comparison is performed on adjusted MO dates we produced to remove known differences in inter-sensor calibration of Tbs and masking techniques used to develop the original MO date products. These adjustments result in a more consistent set of input Tbs for the algorithms. Tests of significance indicate that the trends in the time series of annual mean MO dates for the PMW and AHRA are statistically different for the majority of the Arctic Ocean including the Laptev, E. Siberian, Chukchi, Beaufort, and central Arctic regions with mean differences as large as 38.3 days in the Barents Sea. Trend agreement improves for our more consistent MO dates for nearly all regions. Mean differences remain large, primarily due to differing sensitivity of in-algorithm thresholds and larger uncertainties in thin-ice regions.

  15. Mutation analysis of the chromosome 14q24.3 dihydrolipoyl succinyltransferase (DLST) gene in patients with early-onset Alzheimer disease.

    PubMed

    Cruts, M; Backhovens, H; Van Gassen, G; Theuns, J; Wang, S Y; Wehnert, A; van Duijn, C M; Karlsson, T; Hofman, A; Adolfsson, R

    1995-10-13

    Linkage analysis studies have indicated that the chromosome band 14q24.3 harbours a major gene for familial early-onset Alzheimer's disease (AD). Recently we localized the chromosome 14 AD gene (AD3) in the 6.4 cM interval between the markers D14S289 and D14S61. We mapped the gene encoding dihydrolipoyl succinyltransferase (DLST), the E2k component of human alpha-ketoglutarate dehydrogenase complex (KGDHC), in the AD3 candidate region using yeast artificial chromosomes (YACs). The DLST gene is a candidate for the AD3 gene since deficiencies in KGDHC activity have been observed in brain tissue and fibroblasts of AD patients. The 15 exons and the promoter region of the DLST gene were analysed for mutations in chromosome 14 linked AD cases and in two series of unrelated early-onset AD cases (onset age < 55 years). Sequence variations in intronic sequences (introns 3, 5 and 10) or silent mutations in exonic sequences (exons 8 and 14) were identified. However, no AD related mutations were observed, suggesting that the DLST gene is not the chromosome 14 AD3 gene.

  16. Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes)

    PubMed Central

    Oh, Annie; Pearce, Jacqueline W.; Gandolfi, Barbara; Creighton, Erica K.; Suedmeyer, William K.; Selig, Michael; Bosiack, Ann P.; Castaner, Leilani J.; Whiting, Rebecca E. H.; Belknap, Ellen B.; Lyons, Leslie A.; Aderdein, Danielle; Alves, Paulo C.; Barsh, Gregory S.; Beale, Holly C.; Boyko, Adam R.; Castelhano, Marta G.; Chan, Patricia; Ellinwood, N. Matthew; Garrick, Dorian J.; Helps, Christopher R.; Kaelin, Christopher B.; Leeb, Tosso; Lohi, Hannes; Longeri, Maria; Malik, Richard; Montague, Michael J.; Munday, John S.; Murphy, William J.; Pedersen, Niels C.; Rothschild, Max F.; Swanson, William F.; Terio, Karen A.; Todhunter, Rory J.; Warren, Wesley C.

    2017-01-01

    African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management. PMID:28322220

  17. Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome.

    PubMed

    Chen, Jinyun; Etzel, Carol J; Amos, Christopher I; Zhang, Qing; Viscofsky, Nancy; Lindor, Noralane M; Lynch, Patrick M; Frazier, Marsha L

    2009-11-01

    Lynch syndrome is an autosomal dominant syndrome of familial malignancies resulting from germ line mutations in DNA mismatch repair (MMR) genes. Our goal was to take a pathway-based approach to investigate the influence of polymorphisms in cell cycle-related genes on age of onset for Lynch syndrome using a tree model. We evaluated polymorphisms in a panel of cell cycle-related genes (AURKA, CDKN2A, TP53, E2F2, CCND1, TP73, MDM2, IGF1, and CDKN2B) in 220 MMR gene mutation carriers from 129 families. We applied a novel statistical approach, tree modeling (Classification and Regression Tree), to the analysis of data on patients with Lynch syndrome to identify individuals with a higher probability of developing colorectal cancer at an early age and explore the gene-gene interactions between polymorphisms in cell cycle genes. We found that the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 variant genotype, AURKA wild-type genotype, and CCND1 variant genotype had the youngest age of onset, with a 45-year median onset age, while the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 wild-type genotype, and AURKA variant genotype had the latest median age of onset, which was 70 years. Furthermore, we found evidence of a possible gene-gene interaction between E2F2 and AURKA genes related to CRC age of onset. Polymorphisms in these cell cycle-related genes work together to modify the age at the onset of CRC in patients with Lynch syndrome. These studies provide an important part of the foundation for development of a model for stratifying age of onset risk among those with Lynch syndrome.

  18. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    PubMed Central

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  19. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  20. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    ERIC Educational Resources Information Center

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  1. Verbal Behavior in Young Children with Autism Spectrum Disorders at the Onset of an Early Behavioral Intervention Program

    ERIC Educational Resources Information Center

    Rivard, Melina; Forget, Jacques

    2012-01-01

    The scope of this study was direct observation of verbal behaviors of 14 children with autism spectrum disorders at the onset of an early behavioral intervention (EBI) program delivered in a public services agency. Objectives were to (1) describe frequencies of vocal, verbal, and listener behaviors; (2) evaluate the relationship between the…

  2. The E23K and A190A variations of the KCNJ11 gene are associated with early-onset type 2 diabetes and blood pressure in the Chinese population.

    PubMed

    Zhuang, Langen; Zhao, Yu; Zhao, Weijing; Li, Ming; Yu, Ming; Lu, Ming; Zhang, Rong; Ge, Xiaoxu; Zheng, Taishan; Li, Can; Yin, Jun; Yin, Jingyuan; Bao, Yuqian; Liu, Limei; Jia, Weiping; Liu, Yanjun

    2015-06-01

    Conflicting associations between define (KCNJ11) variations and susceptibility to late-onset (>40 years old) type 2 diabetes mellitus (T2DM) have been reported in different ethnic groups. We investigated whether the E23K (G→A, rs5219) or A190A (C→T, rs5218) variations in KCNJ11 are associated with early-onset T2DM and blood pressure in the Chinese population. Case-control study of 175 unrelated Chinese patients with early-onset T2DM (age of onset <40 years old) who receive (ins+, n = 57) or do not receive insulin (ins-, n = 118), and 182 non-diabetic control subjects. PCR-direct sequencing was performed to genotype E23K and A190A; the genotypic frequencies and associations with clinical characteristics were analyzed. The genotypic frequencies of E23K-GA+AA were higher and A190A-TT was lower in the early-onset T2DM group, especially the T2D-ins+ group, compared to the non-diabetic control group (p < 0.01 or 0.05, respectively). In non-diabetic subjects, E23K-AA carriers had significantly higher 2 h plasma glucose and lower 2 h insulin than E23K-GG carriers (both p < 0.05). A190A-TT or E23K-GG carriers had higher systolic blood pressure (SBP) than CC or AA carriers in the non-diabetic control and T2DM groups (both p < 0.05). In the T2DM ins+ group, E23K-AA carriers had lower onset age and duration of diabetes and higher BMI than GG carriers, and A190A-TT carriers had higher SBP than CC carriers (all p < 0.05). The E23K-GA or AA genotypes may increase the susceptibility to early-onset T2DM, while A190A-TT may protect against early-onset T2DM. On the other hand the A190A-TT or E23K-GG genotypes may increase the risk of hypertension in the Chinese population.

  3. Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity

    PubMed Central

    McIlwrick, Silja; Pohl, Tobias; Chen, Alon; Touma, Chadi

    2017-01-01

    Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body’s main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS. PMID:28261058

  4. MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

    PubMed Central

    Arshad, Ahmad R.; Sulaiman, Siti A.; Saperi, Amalia A.; Jamal, Rahman; Mohamed Ibrahim, Norlinah; Abdul Murad, Nor Azian

    2017-01-01

    Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis. PMID:29163029

  5. A neurally inspired musical instrument classification system based upon the sound onset.

    PubMed

    Newton, Michael J; Smith, Leslie S

    2012-06-01

    Physiological evidence suggests that sound onset detection in the auditory system may be performed by specialized neurons as early as the cochlear nucleus. Psychoacoustic evidence shows that the sound onset can be important for the recognition of musical sounds. Here the sound onset is used in isolation to form tone descriptors for a musical instrument classification task. The task involves 2085 isolated musical tones from the McGill dataset across five instrument categories. A neurally inspired tone descriptor is created using a model of the auditory system's response to sound onset. A gammatone filterbank and spiking onset detectors, built from dynamic synapses and leaky integrate-and-fire neurons, create parallel spike trains that emphasize the sound onset. These are coded as a descriptor called the onset fingerprint. Classification uses a time-domain neural network, the echo state network. Reference strategies, based upon mel-frequency cepstral coefficients, evaluated either over the whole tone or only during the sound onset, provide context to the method. Classification success rates for the neurally-inspired method are around 75%. The cepstral methods perform between 73% and 76%. Further testing with tones from the Iowa MIS collection shows that the neurally inspired method is considerably more robust when tested with data from an unrelated dataset.

  6. The role of monogenic disease in children with very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Baldassano, Robert N

    2017-10-01

    Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions. VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options. Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways, these children may allow for true precision medicine with targeted therapy and improved disease course.

  7. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

    PubMed

    Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

    2015-04-01

    Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early onset autoinflammatory syndrome

    PubMed Central

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M.; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J.; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T.; Zaal, Kristien; Chandrasekharappa, Settara C.; Hanson, Eric P.; Yu, Zhen; Mullikin, James C.; Hasni, Sarfaraz A.; Wertz, Ingrid; Ombrello, Amanda K.; Stone, Deborah L.; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K.; Leavis, Helen L.; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D.; Gül, Ahmet; Siegel, Richard M.; Boehm, Manfred; Milner, Joshua D.; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M.; Kastner, Daniel L.; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity1. Herein we describe a new syndrome caused by high penetrance heterozygous germline mutations in the NFκB regulatory protein TNFAIP3 (A20) in six unrelated families with early onset systemic inflammation. The syndrome resembles Behçet’s disease (BD), which is typically considered a polygenic disorder with onset in early adulthood2. A20 is a potent inhibitor of the NFκB signaling pathway3. TNFAIP3 mutant truncated proteins are likely to act by haploinsufficiency since they do not exert a dominant-negative effect in overexpression experiments. Patients’ cells show increased degradation of IκBα and nuclear translocation of NFκB p65, and increased expression of NFκB-mediated proinflammatory cytokines. A20 restricts NFκB signals via deubiquitinating (DUB) activity. In cells expressing the mutant A20 protein, there is defective removal of K63-linked ubiquitin from TRAF6, NEMO, and RIP1 after TNF stimulation. NFκB-dependent pro-inflammatory cytokines are potential therapeutic targets for these patients. PMID:26642243

  9. Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

    PubMed

    Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-10-06

    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Age of onset of marijuana use and executive function.

    PubMed

    Gruber, Staci A; Sagar, Kelly A; Dahlgren, Mary Kathryn; Racine, Megan; Lukas, Scott E

    2012-09-01

    Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In this study, the authors hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function, more poorly than control subjects and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups, and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly 3 times as much MJ per week relative to the late onset smokers. Age of onset, frequency, and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  11. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?

    PubMed Central

    2015-01-01

    Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea. PMID:26706916

  12. Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q.

    PubMed

    Holmans, Peter; Zubenko, George S; Crowe, Raymond R; DePaulo, J Raymond; Scheftner, William A; Weissman, Myrna M; Zubenko, Wendy N; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G; Marta, Diana H; Adams, Philip; Knowles, James A; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F

    2004-06-01

    A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD.

  13. Copy number variations in "classical" obesity candidate genes are not frequently associated with severe early-onset obesity in children.

    PubMed

    Windholz, Jan; Kovacs, Peter; Schlicke, Marina; Franke, Christin; Mahajan, Anubha; Morris, Andrew P; Lemke, Johannes R; Klammt, Jürgen; Kiess, Wieland; Schöneberg, Torsten; Pfäffle, Roland; Körner, Antje

    2017-05-01

    Obesity is genetically heterogeneous and highly heritable, although polymorphisms explain the phenotype in only a small proportion of obese children. We investigated the presence of copy number variations (CNVs) in "classical" genes known to be associated with (monogenic) early-onset obesity in children. In 194 obese Caucasian children selected for early-onset and severe obesity from our obesity cohort we screened for deletions and/or duplications by multiplex ligation-dependent probe amplification reaction (MLPA). As we found one MLPA probe to interfere with a polymorphism in SIM1 we investigated its association with obesity and other phenotypic traits in our extended cohort of 2305 children. In the selected subset of most severely obese children, we did not find CNV with MLPA in POMC, LEP, LEPR, MC4R, MC3R or MC2R genes. However, one SIM1 probe located at exon 9 gave signals suggestive for SIM1 insufficiency in 52 patients. Polymerase chain reaction (PCR) analysis identified this as a false positive result due to interference with single nucleotide polymorphism (SNP) rs3734354/rs3734355. We, therefore, investigated for associations of this polymorphism with obesity and metabolic traits in our extended cohort. We found rs3734354/rs3734355 to be associated with body mass index-standard deviation score (BMI-SDS) (p = 0.003), but not with parameters of insulin metabolism, blood pressure or food intake. In our modest sample of severely obese children, we were unable to find CNVs in well-established monogenic obesity genes. Nevertheless, we found an association of rs3734354 in SIM1 with obesity of early-onset type in children, although not with obesity-related traits.

  14. Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats.

    PubMed

    Ofri, Ron; Reilly, Christopher M; Maggs, David J; Fitzgerald, Paul G; Shilo-Benjamini, Yael; Good, Kathryn L; Grahn, Robert A; Splawski, Danielle D; Lyons, Leslie A

    2015-08-01

    A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness.

  15. Slit ventricle syndrome and early-onset secondary craniosynostosis in an infant

    PubMed Central

    Ryoo, Hyun Gee; Kim, Seung-Ki; Cheon, Jung-Eun; Lee, Ji Yeoun; Wang, Kyu-Chang; Phi, Ji Hoon

    2014-01-01

    Patient: Female, 14 months Final Diagnosis: Slit ventricle syndrome Symptoms: Hydrocephalus • lethargy and seizure • vomiting Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Challenging differential diagnosis Background: Shunt surgery is a common solution for hydrocephalus in infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset complications after shunt placement; these 2 conditions occasionally occur together. Case Report: We report a case of early-onset secondary craniosynostosis with slit ventricle syndrome after shunt surgery in an infant, which led to a catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her head circumference (HC) gradually decreased to approximately the 5th percentile for her age group after shunt surgery. Seven months later, she developed increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt malfunction. Her symptoms were temporarily relieved, but she repeatedly visited the emergency room (ER) for the same symptoms and finally collapsed, with an abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence of sagittal synostosis at 7 months after initial shunt surgery. After reviewing all clinical data, slit ventricle syndrome combined with secondary craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt revision was performed, and the increased ICP signs subsided in the following days. Conclusions: Clinical suspicion and long-term HC monitoring are important in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after shunt surgery, even in infants and young children. PMID:24944727

  16. Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes.

    PubMed

    Chidambaram, Manickam; Liju, Samuel; Saboo, Banshi; Sathyavani, Kumpatla; Viswanathan, Vijay; Pankratz, Nathan; Gross, Myron; Mohan, Viswanathan; Radha, Venkatesan

    2016-12-01

    To evaluate the association of 87 genetic variants previously associated with type 2 diabetes mellitus (T2DM) in genome-wide association studies of populations of European ancestry in an Asian Indian population with early-onset type 2 diabetes mellitus (EOT2DM). The study groups comprised of 877 type 2 diabetes individuals, 436 individuals with EOT2DM (age at diagnosis below 35 years), 441 individuals with older T2DM (diagnosis at 35 years or greater) and controls with normal glucose tolerance (NGT) (n = 400 younger than 35 years; n = 438 older than 35 years). The participants were genotyped for 87 SNPs from 44 genes and 27 intergenic loci. Associations were tested using logistic regression. All the variants in TCF7L2 and CDKN2A/2B showed study-wide significance (p < 1.4 × 10 -4 ) with T2DM, but only rs7903146, rs12243326, rs12255372 of TCF7L2 and rs7020996 of CDKN2A/2B showed study-wide significance (p < 1.4 × 10 -4 ) with EOT2DM in this population. In addition, an intergenic SNP on chromosome 1 (rs10493685) was also shown to be study-wide significant (p = 7.1 × 10 -6 ). Several additional SNPs previously associated with T2DM reached borderline significance in this study, but may have been limited by relatively low sample numbers. Various other SNPs of T2DM were not associated with EOT2DM. Some of the variants in TCF7L2 and CDKN2A/2B associated with T2DM are associated with EOT2DM as well. An intergenic SNP on chromosome 1p31 showed association only with early-onset T2DM in this Asian Indian population. The lack of association with many other SNPs of T2DM may be a reflection of the lack of power of the study, sample size, differences in the frequencies of genetic polymorphisms in different ethnic groups, effect sizes, as well as ancestral differences in pattern of LD between the genetic variants involved in early- and late-onset T2DM.

  17. Staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.

    PubMed

    Fournier, A; Voirol, P; Krähenbühl, M; Bonnemain, C-L; Fournier, C; Dupuis-Lozeron, E; Pantet, O; Pagani, J-L; Revelly, J-P; Sadeghipour, F; Eggimann, P; Que, Y-A

    2017-03-01

    Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.

  18. A Follow-up Study of Early Onset Psychosis: Comparison between Outcome Diagnoses of Schizophrenia, Mood Disorders, and Personality Disorders.

    ERIC Educational Resources Information Center

    McClellan, Jon M.; And Others

    1993-01-01

    This study of 95 youths previously diagnosed with psychotic disorders found that at follow-up, 24 had a diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders, and 1 with schizo-affective disorder. The study confirmed findings regarding early onset schizophrenia and psychotic mood disorders and emphasized the…

  19. "I Need a Cigarette"--The Effects of Cigarette Smoking on Depression and Anxiety of Youth with Early Onset Schizophrenia

    ERIC Educational Resources Information Center

    Chen, Ya-Ling; Rittner, Barbara; Maguin, Eugene; Dziadaszek, Shannon

    2017-01-01

    The aim of this research was to examine effects of cigarette smoking on depression and anxiety among children and adolescents (youth) with early onset schizophrenia and/or psychosis. Data were obtained from the national evaluation of the Comprehensive Community Mental Health Services for Children and Their Families Program (CMHS Program). Cubic…

  20. The DYT1 gene on 9q34 is responsible for most cases of early limb-onset idiopathic torsion dystonia in non-Jews

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kramer, P.L.; Heiman, G.A.; Leon, D. de

    1994-09-01

    Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent markers within a 2-cM region. The associated haplotype occurs in >90% of early limb-onset AJ cases. The authors examined seven non-Jewish ITD families of northern European and French Canadian descent to determine the extent to which early-onset ITD in non-Jews maps to DYT1. Results are consistent with linkage to the DYT1 region. Affected individualsmore » in these families are clinically similar to the AJ cases, i.e., the site of onset is predominantly in the limbs and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably represent different mutations in the DYT1 gene. The two French Canadian families, however, display the same haplotype. Estimates of penetrance in non-Jewish families range from .40 to .75. They identified disease gene carriers and, with adjustments for age at onset, obtained a direct estimate of penetrance of .46. This is consistent with estimates of 30%-40% in the AJ population. Two other non-Jewish families with atypical ITD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia. 26 refs., 1 fig., 3 tabs.« less

  1. Form and Function in Early Clause-Combining

    ERIC Educational Resources Information Center

    Lustigman, Lyle; Berman, Ruth A.

    2016-01-01

    The study characterizes developmental trends in early Hebrew clause-combining (CC) by analyzing the interplay between linguistic form and communicative function in different interactional settings. Analysis applied to all utterances produced by three children aged 2;0-3;0 who combined two or more clauses, either self-initiated or on the basis of…

  2. Plant macrofossil evidence for an early onset of the Holocene summer thermal maximum in northernmost Europe

    PubMed Central

    Väliranta, M.; Salonen, J. S.; Heikkilä, M.; Amon, L.; Helmens, K.; Klimaschewski, A.; Kuhry, P.; Kultti, S.; Poska, A.; Shala, S.; Veski, S.; Birks, H. H.

    2015-01-01

    Holocene summer temperature reconstructions from northern Europe based on sedimentary pollen records suggest an onset of peak summer warmth around 9,000 years ago. However, pollen-based temperature reconstructions are largely driven by changes in the proportions of tree taxa, and thus the early-Holocene warming signal may be delayed due to the geographical disequilibrium between climate and tree populations. Here we show that quantitative summer-temperature estimates in northern Europe based on macrofossils of aquatic plants are in many cases ca. 2 °C warmer in the early Holocene (11,700–7,500 years ago) than reconstructions based on pollen data. When the lag in potential tree establishment becomes imperceptible in the mid-Holocene (7,500 years ago), the reconstructed temperatures converge at all study sites. We demonstrate that aquatic plant macrofossil records can provide additional and informative insights into early-Holocene temperature evolution in northernmost Europe and suggest further validation of early post-glacial climate development based on multi-proxy data syntheses. PMID:25858780

  3. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    PubMed Central

    Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

    2011-01-01

    Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

  4. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

    PubMed

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

    2005-02-22

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

  5. The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of early-life events

    PubMed Central

    Bauer, Patricia J.; Larkina, Marina

    2013-01-01

    The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session, they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children ages 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children ages 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647

  6. [Late-onset Group B Streptococcus disease in twins delivered by caesarean section].

    PubMed

    Escolano Serrano, S; Ruiz Alcántara, I; Alfonso Diego, J; González Muñoz, A; Gastaldo Simeón, E

    2015-01-01

    Group B Streptococcus (GBS) is a commensal pathogen of the gut microflora with a well-established role in the aetiology of early and late onset GBS infections in the newborn. The incidence of early onset infections by vertical transmission has been drastically reduced in recent decades with the use of intravenous intrapartum prophylaxis. Progress in risk factor detection and prophylaxis of late-onset infection has however remained static. The ongoing modifications and improvements of the guidelines regarding prophylaxis, risk factors and prevention of the early-onset GBS disease have not addressed late-onset GBS infection in detail. The following cases illustrate the presence of grey areas in current guidelines and in the knowledge of the pathogenesis of late-onset disease. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  7. The School Psychologist's Primer on Early Onset Schizophrenia: A Review of Research Regarding Epidemiology, Etiology, Assessment, and Treatment

    ERIC Educational Resources Information Center

    Hernandez, Rafael J. C.; Rime, W. Jeremy; Jimerson, Shane R.

    2013-01-01

    The purpose of this article is to provide school psychologists and other educational professionals with important information regarding the epidemiology, etiology, assessment, and treatment of early onset schizophrenia (EOS). The central aim herein is to bring science to practice by succinctly highlighting key considerations for school…

  8. Age at onset typology in opioid dependent men: an exploratory study.

    PubMed

    De, Biswajit; Mattoo, Surendra K; Basu, Debasish

    2002-04-01

    This study attempted to apply age at onset typology in ICD-10 diagnosed opioid dependence. The sample comprised 80 men seeking treatment at an addiction clinic. The measures included socio-demographic and clinical profile, Severity of Opioid Dependence Questionnaire, Modified Sensation Seeking Scale, Multiphasic Personality Questionnaire (MPQ) and Family History Assessment Module. A cut-off age of 20/21 years for an early-onset late-onset typology of opioid dependence was obtained using two methods - the modal age at onset method and one-third sample by age at onset method. The early onset group showed significant differences in terms of it being more often younger, urban, unmarried, wage earning or students, using oral opioids (not heroin or injectables), showing higher lifetime use and dependence of sedatives, earlier onset of use and dependence of sedatives and tobacco, and higher global psychopathology in terms of MPQ. The early onset group also showed statistically insignificant trends for lesser use and dependence of alcohol, higher severity of opioid dependence, more legal and less social complications, higher sensation seeking (except boredom susceptibility), and more frequent substance dependence in first degree relatives. The age at onset typology in opioid dependence appears to be feasible and having some similarities to similar typology in alcoholism.

  9. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1.

    PubMed

    Steichen-Gersdorf, Elisabeth; Lorenz-Depiereux, Bettina; Strom, Tim Matthias; Shaw, Nicholas J

    2015-07-01

    Autosomal recessive hypophosphatemic rickets 2 (ARHR2) is a rare form of renal tubular phosphate wasting disorder. Loss of function mutations of the ecto-nucleotide pyrophosphatase/pyrophosphodiesterase 1 gene (ENPP1) causes a wide spectrum of phenotypes, ranging from lethal generalized arterial calcification of infancy to hypophosphatemic rickets with hypertension. Hearing loss was not previously thought to be one of the features of the disease entities and was merely regarded as a complication rather than a part of the disease. We report two children who presented in mid to late childhood with progressive varus deformity of their legs due to hypophosphatemic rickets caused by mutations in the ENPP1 gene. Both children had evidence of progressive hearing loss requiring the use of hearing aids. This report of two unrelated infants with compound heterozygous mutations in ENPP1 and previously published cases confirms that mild to moderate hearing loss is frequently associated with ARHR2. Early onset conductive hearing loss may further distinguish the autosomal recessive ENPP1 related type from other types of hypophosphatemia.

  10. Caregiver burden and psychosocial services in patients with early and late onset Alzheimer's disease.

    PubMed

    Grønning, Helene; Kristiansen, Susanne; Dyre, Dorte; Rahmani, Abdul; Gyllenborg, Jesper; Høgh, Peter

    2013-07-01

    The purpose of the study was to analyse caregiver burden and consumption of psychosocial services in a consecutive group of patients with early onset Alzheimer's disease (EOAD) compared with a matching group with late onset Alzheimer's disease (LOAD). This was a case-control study with 42 patients who were matched according to disease severity at the time of diagnosis. Caregivers in both groups were interviewed using the Neuro Psychiatric Inventory (NPI), the Activities of Daily Living (ADL) scale and the Resource Utilization in Dementia scale. The quantitative outcomes were compared statistically. The EOAD group had a significantly higher ADL score than the LOAD group. There was a trend towards caregivers in the LOAD group spending more time helping the patients, and they needed more social services than the EOAD group. NPI scores were not significantly different, but a tendency towards a higher caregiver burden in the EOAD group was observed. The higher caregiver burden in patients with EOAD--despite a better ADL function than LOAD patients--suggests that the existing psychosocial services might be particularly insufficient for caregivers in EOAD. The study was funded by a three-month scholarship grant from the research fund at Roskilde Hospital. not relevant.

  11. Neurocognition in early-onset schizophrenia and schizoaffective disorders.

    PubMed

    Hooper, Stephen R; Giuliano, Anthony J; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Frazier, Jean A; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A

    2010-01-01

    We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.

  12. Somatic mutations in early onset luminal breast cancer

    PubMed Central

    de Lyra, Eduardo Carneiro; Hirata Katayama, Maria Lucia; Maistro, Simone; de Vasconcellos Valle, Pedro Wilson Mompean; de Lima Pereira, Gláucia Fernanda; Rodrigues, Lívia Munhoz; de Menezes Pacheco Serio, Pedro Adolpho; de Gouvêa, Ana Carolina Ribeiro Chaves; Geyer, Felipe Correa; Basso, Ricardo Alves; Pasini, Fátima Solange; del Pilar Esteves Diz, Maria; Brentani, Maria Mitzi; Guedes Sampaio Góes, João Carlos; Chammas, Roger; Boutros, Paul C.; Koike Folgueira, Maria Aparecida Azevedo

    2018-01-01

    Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. PMID:29854292

  13. Psychosocial impact of early onset dementia among caregivers.

    PubMed

    Kimura, Nathália R S; Maffioletti, Virgínia L R; Santos, Raquel L; Baptista, Maria Alice Tourinho; Dourado, Marcia C N

    2015-01-01

    There is growing recognition of early onset dementia (EOD) as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD) and their caregivers. To analyze the psychosocial impact of EOD in family caregivers. The study design was qualitative. Nine EOD caregivers (7 women) were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

  14. Juvenile-onset myasthenia gravis: autoantibody status, clinical characteristics and genetic polymorphisms.

    PubMed

    Hong, Yu; Skeie, Geir Olve; Zisimopoulou, Paraskevi; Karagiorgou, Katerina; Tzartos, Socrates J; Gao, Xiang; Yue, Yao-Xian; Romi, Fredrik; Zhang, Xu; Li, Hai-Feng; Gilhus, Nils Erik

    2017-05-01

    Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years). JMG patients were classified into two subgroups: the very early onset group (<8 years) and puberty onset group (8-18 years). The very early onset MG patients had a higher proportion of ocular MG and thymus hyperplasia, compared with puberty onset MG and young adult MG (P < 0.05). AChR antibodies were found in majority of JMG patients and were associated with more severe disease (P < 0.05), while other antibodies were rare in JMG. Moreover, the very early onset MG had a more prominent genetic predisposition than puberty and adult MG, affecting the susceptible genes CHRNA1 and CTLA4. JMG has the same pathogenic background as adult MG, but has typical clinical features and a prominent genetic predisposition in very early onset patients (<8 years). Specific therapeutic considerations are needed.

  15. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons.

    PubMed

    Nicolas, Gaël; Wallon, David; Charbonnier, Camille; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Coutant, Sophie; Le Guennec, Kilan; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Munter, Hans Markus; Bourque, Guillaume; Auld, Daniel; Montpetit, Alexandre; Lathrop, Mark; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Sauvée, Mathilde; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Ceccaldi, Mathieu; Chamard, Ludivine; Blanc, Frédéric; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

    2016-05-01

    Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes.

  16. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

    PubMed

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB-mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.

  17. Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease.

    PubMed

    Muchnik, Carolina; Olivar, Natividad; Dalmasso, María Carolina; Azurmendi, Pablo Javier; Liberczuk, Cynthia; Morelli, Laura; Brusco, Luis Ignacio

    2015-10-01

    Presenilin 2 gene (PSEN2) mutations account for <5% of all early-onset familial Alzheimer's disease (EOFAD) cases and only 13 have strong evidence for pathogenicity. We aimed to investigate the presence of PSEN2 mutation p.N141I and characterize the clinical phenotypes in 2 Argentine pedigrees (AR2 and AR3) with clinical symptoms of EOFAD. Detailed clinical assessments and genetic screening for PSEN2 and APOE genes were carried out in 19 individuals of AR2 and AR3 families. The p.N141I mutation was identified in all affected subjects and was associated with prominent early onset, rapidly progressive dementia, neurologic, and behavioral symptoms. AR2 and AR3 families share the same Volga German ancestry as all the families reported presenting this mutation. To our knowledge, this is the first report of PSEN2 mutation p.N141I in Argentina and even more, in South America. Our contribution increases the total number of described families carrying this mutation and help to improve the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

    PubMed

    Paulo, Paula; Maia, Sofia; Pinto, Carla; Pinto, Pedro; Monteiro, Augusta; Peixoto, Ana; Teixeira, Manuel R

    2018-04-01

    Considering that mutations in known prostate cancer (PrCa) predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS) in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

  19. Comparison of clinical characteristics between familial and non-familial early onset Alzheimer's disease.

    PubMed

    Joshi, Aditi; Ringman, John M; Lee, Albert S; Juarez, Kevin O; Mendez, Mario F

    2012-10-01

    Although familial Alzheimer's disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.

  20. A large early-onset Alzheimer`s disease pedigree linked to chromosome 14q24.3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hannequin, D.; Campion, D.; Brice, A.

    1994-09-01

    A large French pedigree including 34 subjects with early-onset progressive dementia was identified. In patients, the mean age-at-onset was 46 {plus_minus} 3.5 (SD) years and the mean age at death 52.6 {plus_minus} 5.7 (SD) years. No evidence for anticipation or genetic imprinting was found. Twelve patients were clinically diagnosed as probable Alzheimer`s disease (AD) according to the NINCDS-ADRDA criteria. Myoclonus and extrapyramidal signs were common and seizures were found in all affected subjects. At autopsy, neuropathological changes typical of AD were present in two brains. A significant lod score of 5.38 was observed at a recombination fraction of {theta} =more » 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. Furthermore, no obligate recombinant was observed with markers D14S77 and D14S71. Typing other genetic markers in this region will allow us to localize more precisely the pathological gene.« less

  1. A prospective, randomized comparison of an in-line heat moisture exchange filter and heated wire humidifiers: rates of ventilator-associated early-onset (community-acquired) or late-onset (hospital-acquired) pneumonia and incidence of endotracheal tube occlusion.

    PubMed

    Kirton, O C; DeHaven, B; Morgan, J; Morejon, O; Civetta, J

    1997-10-01

    To compare the performance of an in-line heat moisture exchanging filter (HMEF) (Pall BB-100; Pall Corporation; East Hills, NY) to a conventional heated wire humidifier (H-wH) (Marquest Medical Products Inc., Englewood, Colo) in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia (VAP) and the rate of endotracheal tube occlusion. This report describes a prospective, randomized trial of 280 consecutive trauma patients in a 20-bed trauma ICU (TICU). All intubated patients not ventilated elsewhere in the medical center prior to their TICU admission were randomized to either an in-line HMEF or a H-wH in the breathing circuit. Ventilator circuits were changed routinely every 7 days, and closed system suction catheters were changed every 3 days. HMEFs were changed every 24 h, or more frequently if necessary. A specific endotracheal tube suction and lavage protocol was not employed. Patients were dropped from the HMEF group if the filter was changed more than three times a day or the patient was placed on a regimen of ultra high-frequency ventilation. The Centers for Disease Control and Prevention (CDC) criteria for diagnosis of pneumonia were used; early-onset, community-acquired pneumonia was defined if CDC criteria were met in < or =3 days, and late-onset, hospital-acquired pneumonia was defined if criteria were met in >3 days. Laboratory and chest radiograph interpretation were blinded. The patient ages ranged from 15 to 95 years in the HMEF group and 16 to 87 years in the H-wH group (p=not significant), with a mean age of 46 years and 48 years, respectively. The male to female ratio ranged between 78 to 82%/22 to 18%, respectively, and 55% of all admissions were related to blunt trauma, 40% secondary to penetrating trauma, and 5% to major burns. There was no difference in Injury Severity Score (ISS) between the two groups. Moreover, there was no significant difference in mean ISS among those who did not develop pneumonia and those

  2. THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.

    PubMed

    Cheng, Fu Bo; Ozelius, Laurie J; Wan, Xin Hua; Feng, Jia Chun; Ma, Ling Yan; Yang, Ying Mai; Wang, Lin

    2012-02-01

    Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.

  3. Early-versus Late-Onset Alzheimer Disease: Long-Term Functional Outcomes, Nursing Home Placement, and Risk Factors for Rate of Progression.

    PubMed

    Wattmo, Carina; Wallin, Åsa K

    2017-01-01

    Whether age at onset influences functional deterioration in Alzheimer disease (AD) is unclear. We, therefore, investigated risk factors for progression in activities of daily living (ADL) and nursing home placement (NHP) in cholinesterase inhibitor (ChEI)-treated patients with early-onset AD (EOAD) versus late-onset AD (LOAD). This 3-year, prospective, observational, multicenter study included 1,017 participants with mild-to-moderate AD; 143 had EOAD (onset <65 years) and 874 LOAD (onset ≥65 years). Possible sociodemographic and clinical factors that could affect functional outcome and NHP were analyzed using mixed-effects models and logistic regression, respectively. Younger individuals exhibited longer illness duration before AD diagnosis, whereas 6-month functional response to ChEI therapy, 3-year changes in ADL capacities, time from diagnosis to NHP, and survival time in nursing homes were similar between the groups. In LOAD, a higher ChEI dose, no antidepressant use, and lower education level were protective factors for slower instrumental ADL (IADL) decline. In EOAD, antihypertensives/cardiac therapy implied faster IADL progression but lower risk of NHP. This study highlights the clinical importance of an earlier diagnosis and treatment initiation and the need for functional evaluations in EOAD. Despite the age differences between EOAD and LOAD, a similar need for nursing homes was observed.

  4. Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

    PubMed Central

    Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

    2015-01-01

    Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

  5. Validation of Patient-Reported Outcomes Measurement Information System Short Forms for Use in Childhood-Onset Systemic Lupus Erythematosus.

    PubMed

    Jones, Jordan T; Carle, Adam C; Wootton, Janet; Liberio, Brianna; Lee, Jiha; Schanberg, Laura E; Ying, Jun; Morgan DeWitt, Esi; Brunner, Hermine I

    2017-01-01

    To validate the pediatric Patient-Reported Outcomes Measurement Information System short forms (PROMIS-SFs) in childhood-onset systemic lupus erythematosus (SLE) in a clinical setting. At 3 study visits, childhood-onset SLE patients completed the PROMIS-SFs (anger, anxiety, depressive symptoms, fatigue, physical function-mobility, physical function-upper extremity, pain interference, and peer relationships) using the PROMIS assessment center, and health-related quality of life (HRQoL) legacy measures (Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters [SMILEY], and visual analog scales [VAS] of pain and well-being). Physicians rated childhood-onset SLE activity on a VAS and completed the Systemic Lupus Erythematosus Disease Activity Index 2000. Using a global rating scale of change (GRC) between study visits, physicians rated change of childhood-onset SLE activity (GRC-MD1: better/same/worse) and change of patient overall health (GRC-MD2: better/same/worse). Questionnaire scores were compared in support of validity and responsiveness to change (external standards: GRC-MD1, GRC-MD2). In this population-based cohort (n = 100) with a mean age of 15.8 years (range 10-20 years), the PROMIS-SFs were completed in less than 5 minutes in a clinical setting. The PROMIS-SF scores correlated at least moderately (Pearson's r ≥ 0.5) with those of legacy HRQoL measures, except for the SMILEY. Measures of childhood-onset SLE activity did not correlate with the PROMIS-SFs. Responsiveness to change of the PROMIS-SFs was supported by path, mixed-model, and correlation analyses. To assess HRQoL in childhood-onset SLE, the PROMIS-SFs demonstrated feasibility, internal consistency, construct validity, and responsiveness to change in a clinical setting. © 2016, American College of Rheumatology.

  6. Cerebellar pathology in childhood-onset vs. adult-onset essential tremor.

    PubMed

    Louis, Elan D; Kuo, Sheng-Han; Tate, William J; Kelly, Geoffrey C; Faust, Phyllis L

    2017-10-17

    Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Lifetime romantic attachment style and social adaptation in late-onset depression.

    PubMed

    Paradiso, Sergio; Naridze, Rachelle; Holm-Brown, Erika

    2012-10-01

    Measuring social adjustment (including attachment style and current social adaptation) in late-life depression may support planning secondary prevention, rehabilitation, and treatment. Insecure attachment style is a risk factor for developing new depression, and social adjustment may constitute a problem after symptoms abatement. Few studies have examined attachment style and social adjustment in late-onset depression. Subjects 50 years of age and older with early-onset (n = 35), late-onset DSM-IV unipolar depression (n = 38), and never-depressed volunteers (n = 47) were assessed with a widely used measure of attachment style (the Experiences in Close Relationship Scale). Social adjustment was measured using the Social Adjustment Scale. Both early-onset and late-onset patients with depression showed greater insecure attachment and poorer social adaptation compared with never-depressed volunteers. No difference was found between early-onset and late-onset patients with depression on attachment style or social adjustment. There were no significant differences between late-life depression in remission or current on attachment or social adaptation. Insecure attachment style may be a risk factor for late-life depression irrespective of the age of onset. Social maladaptation may persist among individuals with late-life depression in remission. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Differentiating early-onset chronic depression from episodic depression in terms of cognitive-behavioral and emotional avoidance.

    PubMed

    Brockmeyer, Timo; Kulessa, Dominika; Hautzinger, Martin; Bents, Hinrich; Backenstrass, Matthias

    2015-04-01

    Although chronic depression is associated with lower global functioning and poorer treatment response than episodic depression, little is known about the differences between these two forms of depression in terms of psychological factors. Thus, the present study aimed at differentiating chronic and episodic depression regarding cognitive-behavioral and emotional avoidance that have been proposed as important risk factors for depression and promising targets for the treatment of depression. Thirty patients with early onset chronic depression were compared with 30 patients with episodic depression and 30 healthy, never-depressed controls in terms of self-reported cognitive-behavioral (social and non-social) and emotional avoidance. Chronically depressed patients reported more avoidance than healthy controls in each of the measures. Moreover, they reported more cognitive-nonsocial and behavioral-nonsocial as well as behavioral-social and emotional avoidance (in the form of restricted emotional expression to others) than patients with episodic depression. This kind of emotional avoidance also separated best between chronically and episodically depressed patients. Furthermore, general emotion avoidance and behavioral-social avoidance were positively correlated with levels of depression in chronically depressed patients. The results are based on self-report data and should thus be interpreted with caution. Additionally, the cross-sectional design limits any causal conclusions. The findings underscore the relevance of cognitive-behavioral and emotional avoidance in differentiating chronic from episodic depression and healthy controls and advocate a stronger focus on maladaptive avoidance processes in the treatment of chronic depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel β-subunit in a case of early-onset phenotype of Liddle syndrome.

    PubMed

    Polfus, Linda M; Boerwinkle, Eric; Gibbs, Richard A; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan; Grove, Megan; Shete, Sanjay; Wallace, Stephanie; Milewicz, Dianna; Hanchard, Neil; Lupski, James R; Hashmi, Syed Shahrukh; Gupta-Malhotra, Monesha

    2016-11-01

    To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations. Drawing upon clinical presentation, 27 genes were selected evidenced to cause monogenic hypertension and matched to the gene-based results. This resulted in the identification of a stop-gain mutation in an epithelial sodium channel (ENaC), SCNN1B , an established Liddle syndrome gene, shared by the child and her father. Interestingly, the father also harbored a missense mutation (p.Trp552Arg) in the α-subunit of the ENaC trimer, SCNN1A , possibly pointing to pseudohypoaldosteronism type I. This case is unique in that we present the early-onset disease and treatment response caused by a canonical stop-gain mutation (p.Arg566*) as well as ENaC digenic hits in the father, emphasizing the utility of WES informing precision medicine.

  10. A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.

    PubMed

    Röhrs, Susanne; Kalthoff, Donata; Beer, Martin

    2014-05-07

    Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Hypothyroidism in late-onset Pompe disease.

    PubMed

    Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle; Whitley, Chester B; Jarnes Utz, Jeanine

    2016-09-01

    In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p < 0.001 compared with the general UMMC adult population). Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.

  12. Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan.

    PubMed

    Rashid, Muhammad U; Muhammad, Noor; Amin, Asim; Loya, Asif; Hamann, Ute

    2017-01-01

    Germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers. Pakistan has one of the highest rates of breast cancer incidence in Asia, where BRCA1/2 small-range mutations account for 17% of early-onset and familial breast/ovarian cancer patients. We report the first study from Pakistan evaluating the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in breast and/or ovarian cancer patients who do not harbor small-range BRCA1/2 mutations. Both BRCA1/2 genes were comprehensively screened for LGRs using multiplex ligation-dependent probe amplification in 120 BRCA1/2 small-range mutations negative early-onset or familial breast/ovarian cancer patients from Pakistan (Group 1). The breakpoints were characterized by long-range PCR- and DNA-sequencing analyses. An additional cohort of 445 BRCA1/2 negative high-risk patients (Group 2) was analyzed for the presence of LGRs identified in Group 1. Three different BRCA1 LGRs were identified in Group 1 (4/120; 3.3%), two of these were novel. Exon 1-2 deletion was observed in two unrelated patients: an early-onset breast cancer patient and another bilateral breast cancer patient from a hereditary breast cancer (HBC) family. Novel exon 20-21 deletion was detected in a 29-year-old breast cancer patient from a HBC family. Another novel exon 21-24 deletion was identified in a breast-ovarian cancer patient from a hereditary breast and ovarian cancer family. The breakpoints of all deletions were characterized. Screening of the 445 patients in Group 2 for the three LGRs revealed ten additional patients harboring exon 1-2 deletion or exon 21-24 deletion (10/445; 2.2%). No BRCA2 LGRs were identified. LGRs in BRCA1 are found with a considerable frequency in Pakistani breast/ovarian cancer cases. Our findings suggest that BRCA1 exons 1-2 deletion and exons 21-24 deletion should be included in the recurrent BRCA1/2 mutations panel for genetic testing of high-risk Pakistani

  13. Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study.

    PubMed

    Charbit-Henrion, Fabienne; Parlato, Marianna; Hanein, Sylvain; Duclaux-Loras, Rémi; Nowak, Jan; Begue, Bernadette; Rakotobe, Sabine; Bruneau, Julie; Fourrage, Cécile; Alibeu, Olivier; Rieux-Laucat, Frédéric; Lévy, Eva; Stolzenberg, Marie-Claude; Mazerolles, Fabienne; Latour, Sylvain; Lenoir, Christelle; Fischer, Alain; Picard, Capucine; Aloi, Marina; Amil Dias, Jorge; Ben Hariz, Mongi; Bourrier, Anne; Breuer, Christian; Breton, Anne; Bronski, Jiri; Buderus, Stephan; Cananzi, Mara; Coopman, Stéphanie; Crémilleux, Clara; Dabadie, Alain; Dumant-Forest, Clémentine; Egritas Gurkan, Odul; Fabre, Alexandre; Fischer, Aude; German Diaz, Marta; Gonzalez-Lama, Yago; Goulet, Olivier; Guariso, Graziella; Gurcan, Neslihan; Homan, Matjaz; Hugot, Jean-Pierre; Jeziorski, Eric; Karanika, Evi; Lachaux, Alain; Lewindon, Peter; Lima, Rosa; Magro, Fernando; Major, Janos; Malamut, Georgia; Mas, Emmanuel; Mattyus, Istvan; Mearin, Luisa M; Melek, Jan; Navas-Lopez, Victor Manuel; Paerregaard, Anders; Pelatan, Cecile; Pigneur, Bénédicte; Pinto Pais, Isabel; Rebeuh, Julie; Romano, Claudio; Siala, Nadia; Strisciuglio, Caterina; Tempia-Caliera, Michela; Tounian, Patrick; Turner, Dan; Urbonas, Vaidotas; Willot, Stéphanie; Ruemmele, Frank M; Cerf-Bensussan, Nadine

    2018-05-18

    An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases (VEO-IBD). The present study aimed at defining how next-generation sequencing (NGS) methods can be used to improve identification of known molecular diagnosis and adapt treatment. 207 children were recruited in 45 Paediatric centres through an international collaborative network (ESPGHAN GENIUS working group) with a clinical presentation of severe VEO-IBD (n=185) or an anamnesis suggestive of a monogenic disorder (n=22). Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing (WES) of parents-child trios. Genetic findings were validated clinically and/or functionally. Molecular diagnosis was achieved in 66/207 children (32%): 61% with small bowel inflammation, 39% with colitis and perianal lesions and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations and identified large exonic copy number variations previously missed by WES. Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

  14. Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse.

    PubMed

    Devlin, M J; Van Vliet, M; Motyl, K; Karim, L; Brooks, D J; Louis, L; Conlon, C; Rosen, C J; Bouxsein, M L

    2014-10-01

    Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8-10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (-54%), trabecular number (-27%), and connectivity density (-82%) (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.

  15. Childhood and adolescent predictors of late onset criminal careers.

    PubMed

    Zara, Georgia; Farrington, David P

    2009-03-01

    This study explores the emergence of a criminal career in adulthood. The main hypothesis tested is that late criminal onset (at age 21 or later) is influenced by early factors that delay antisocial manifestations. The Cambridge Study in Delinquent Development (CSDD) was used to examine early determinants of criminal behavior. 400 Inner London males were followed from ages 8-10 to 48-50, and were classified as follows: 35 late onsetters who were first convicted at age 21 or later, and did not have high self-reported delinquency at ages 10-14 and 15-18; 129 early onsetters first convicted between ages 10 and 20; and 236 unconvicted males. Odds ratios and logistic regression analyses revealed that the best predictors of late onset offenders compared with early onset offenders included nervousness, having few friends at ages 8-10, and not having sexual intercourse by age 18. The best predictors of late onset offenders compared with nonoffenders included teacher-rated anxiousness at ages 12-14 and high neuroticism at age 16. It is concluded that being nervous and withdrawn protected boys against offending in adolescence but that these protective effects tended to wear off after age 21. These findings show that adult offending can be predicted from childhood, and suggest that early intervention might prevent a variety of maladjustment problems and difficulties in adult life.

  16. Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean D.

    2010-01-01

    Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

  17. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    PubMed

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

    PubMed Central

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be

  19. Factors influencing the development of early- or late-onset Parkinson's disease in a cohort of South African patients.

    PubMed

    van der Merwe, Celia; Haylett, William; Harvey, Justin; Lombard, Debbie; Bardien, Soraya; Carr, Jonathan

    2012-10-01

    Neurodegenerative disorders such as Parkinson's disease (PD) contribute significantly to global disease burden. PD can be categorised into early-onset PD (EOPD) with an age at onset (AAO) of ≤50 years and late-onset PD (LOPD) with an AAO of 50 years. To identify factors influencing EOPD and LOPD development in a group of patients in South Africa (SA). A total of 397 unrelated PD patients were recruited from the Movement Disorders Clinic at Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic and environmental data were recorded and associations with PD onset (EOPD v. LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans-speaking (Afrikaner) white patients were analysed separately. Logistic regression analysis showed that ethnicity (p<0.001) and family history (p=0.004) were independently associated with AAO of PD. Average AAO was younger in black, coloured and Afrikaner patients than English-speaking white patients. A positive family history of PD, seen in 31.1% of LOPD patients, was associated with a younger AAO in the study population. These associations may be attributed to specific genetic and/or environmental risk factors that increase PD susceptibility and influence the clinical course of the disorder. More studies on PD in the unique SA populations are required to provide novel insights into mechanisms underlying this debilitating condition.

  20. Usherin defects lead to early-onset retinal dysfunction in zebrafish.

    PubMed

    Dona, Margo; Slijkerman, Ralph; Lerner, Kimberly; Broekman, Sanne; Wegner, Jeremy; Howat, Taylor; Peters, Theo; Hetterschijt, Lisette; Boon, Nanda; de Vrieze, Erik; Sorusch, Nasrin; Wolfrum, Uwe; Kremer, Hannie; Neuhauss, Stephan; Zang, Jingjing; Kamermans, Maarten; Westerfield, Monte; Phillips, Jennifer; van Wijk, Erwin

    2018-05-16

    Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2a rmc1 : c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a b1245 : c.15520_15523delinsTG; p.Ala5174fsTer). Homozygous mutants were viable and displayed no obvious morphological or developmental defects. Immunohistochemical analyses with antibodies recognizing the N- or C-terminal region of the ush2a-encoded protein, usherin, demonstrated complete absence of usherin in photoreceptors of ush2a rmc1 , but presence of the ectodomain of usherin at the periciliary membrane of ush2a b1245 -derived photoreceptors. Furthermore, defects of usherin led to a reduction in localization of USH2 complex members, whirlin and Adgrv1, at the photoreceptor periciliary membrane of both mutants. Significantly elevated levels of apoptotic photoreceptors could be observed in both mutants when kept under constant bright illumination for three days. Electroretinogram (ERG) recordings revealed a significant and similar decrease in both a- and b-wave amplitudes in ush2a rmc1 as well as ush2a b1245 larvae as compared to strain- and age-matched wild-type larvae. In conclusion, this study shows that mutant ush2a zebrafish models present with early-onset retinal dysfunction that is exacerbated by light exposure. These models provide a better understanding of the pathophysiology underlying USH2A-associated RP and a unique opportunity to evaluate future therapeutic strategies. Copyright

  1. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice

    PubMed Central

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Åke

    2005-01-01

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5α-androstane-3β, 17β-diol (3βAdiol). 3βAdiol is estrogenic in ERα or ERβ positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1–/– mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3βAdiol, CYP7B1 performs two major tasks: (i) it allows 3βAdiol to have growth inhibitory effects through ERβ and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3βAdiol. When CYP7B1 is inactivated, 3βAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  2. Imitating actions on objects in early-onset and regressive autism: Effects and implications of task characteristics on performance

    PubMed Central

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2010-01-01

    This study was designed to examine the nature of object imitation performance in early autism. We hypothesized that imitation would be relatively preserved when behaviors on objects resulted in salient instrumental effects. We designed tasks in which, in one condition, the motor action resulted in a salient, meaningful effect on an object, whereas in the other condition, the same action resulted in a less salient effect because of differing object characteristics. The motor aspects of the tasks did not vary across conditions. Four participant groups of 2- to 5-year-olds were examined: 17 children with early-onset autism, 24 children with regressive onset autism, 22 children with developmental delays, and 22 children with typical development. Groups were matched on nonverbal skills, and differences in verbal development were examined as a moderator of imitative ability. Results revealed an interaction of group by condition, with the combined autism group failing more tasks than the combined comparison groups, and failing more tasks in the less salient condition than in the more salient condition, as hypothesized. Analyses of autism subgroups revealed these effects were primarily because of the regression onset group. Accuracy of motor performance was examined by analyzing errors. Among children passing imitative acts, there were no group differences and no condition effects in the number, type, or pattern of performance errors. Among children passing the tasks, the group with autism did not demonstrate more emulation errors (imitating the goal but not the means) than other groups. There was no evidence that either motor or attentional aspects of the tasks contributed to the poorer imitative performance of the children with autism. PMID:20102648

  3. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns).

    PubMed

    Stocker, Martin; van Herk, Wendy; El Helou, Salhab; Dutta, Sourabh; Fontana, Matteo S; Schuerman, Frank A B A; van den Tooren-de Groot, Rita K; Wieringa, Jantien W; Janota, Jan; van der Meer-Kappelle, Laura H; Moonen, Rob; Sie, Sintha D; de Vries, Esther; Donker, Albertine E; Zimmerman, Urs; Schlapbach, Luregn J; de Mol, Amerik C; Hoffman-Haringsma, Angelique; Roy, Madan; Tomaske, Maren; Kornelisse, René F; van Gijsel, Juliette; Visser, Eline G; Willemsen, Sten P; van Rossum, Annemarie M C

    2017-08-26

    Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844

  4. Developmental differences according to age at onset in juvenile bipolar disorder.

    PubMed

    Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Toni, Cristina; Bertini, Nicoletta; Pfanner, Chiara; Berloffa, Stefano; Pari, Cinzia

    2006-12-01

    This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

  5. A longitudinal analysis of early risk factors for adult-onset offending: What predicts a delayed criminal career?

    PubMed

    Zara, Georgia; Farrington, David P

    2010-10-01

    Late-onset offending, at the age of 21 or thereafter, is an underexplored dimension of the criminal career. Our aims were to explore which factors are precursors of late-onset offending, and the extent to which adult criminality can be predicted in childhood and adolescence. This is the first study that defines late-onset offending based on a combination of official records and self-reports. Longitudinal data from the Cambridge Study in Delinquent Development (CSDD) were used. Four hundred and three South London men, followed from ages 8-10 to ages 48-50, were divided into late-starters (LS, n = 51), early-starters (ES, n = 140) and non-offenders (NO, n = 212). LS men were more likely than NO men to have been neurotic, truants or in poor housing at ages 8-10. At ages 12-14, they tended to be neurotic, and at ages 16-18, they had high unemployment and spent time hanging about on the streets. Compared with ES, LS were nervous at ages 8-10, and at age 18 they were more likely to be sexual virgins. Overall, LS men were more similar to NO men before age 21, but more similar to ES men by age 32. Our hypotheses that late-onset offenders would be particularly characterised by neuroticism or nervousness, but that this would buffer rather than fully protect over the life course, were sustained. Intervention to increase the resilience of children and adolescents who are rated as high on neurotic characteristics may lessen the burden that these factors impose in adult life and reduce the risk of a deteriorating quality of life and late onset criminal careers. © 2010 John Wiley & Sons, Ltd.

  6. Early-onset arthritis in retired National Football League players.

    PubMed

    Golightly, Yvonne M; Marshall, Stephen W; Callahan, Leigh F; Guskiewicz, Kevin

    2009-09-01

    Injury has been identified as a potential risk factor for osteoarthritis. However, no previous study has addressed playing-career injuries and subsequent osteoarthritis in a large sample of former athletes. The purpose of this study was to describe the prevalence and determinants of arthritis and osteoarthritis in retired professional football players. Self-reported arthritis prevalence and retrospectively-recalled injury history were examined in a cross-sectional survey of 2,538 retired football players. Football players reported a high incidence of injury from their professional playing days (52.8% reported knee injuries, 74.1% reported ligament/tendon injuries, and 14.2% reported anterior cruciate ligament tears). For those under 60 years, 40.6% of retired NFL players reported arthritis, compared with 11.7% of U.S. males (prevalence ratio = 3.5, 95% CI: 3.3 to 3.7). Within the retired NFL player cohort, osteoarthritis was more prevalent in those with a history of knee injury (prevalence ratio = 1.7, 95% CI: 1.5 to 1.9) and ligament/tendon injury (prevalence ratio = 1.6, 95% CI: 1.4 to 1.9). In males under the age of 60, arthritis is over 3 times more prevalent in retired NFL players than in the general U.S. population. This excess of early-onset arthritis may be due to the high incidence of injury in football.

  7. Adolescent Rats are Resistant to Forming Ethanol Seeking Habits

    PubMed Central

    Serlin, Hannah; Torregrossa, Mary M.

    2015-01-01

    Early age of onset alcohol drinking is significantly more likely to lead to alcohol use disorders (AUDs) than alcohol drinking that begins after the age of 18. Unfortunately, the majority of people in the United States begin drinking in adolescence. Therefore, it is important to understand how early alcohol drinking leads to increased risk for AUDs so that better treatments and prevention strategies can be developed. Adolescents perceive greater rewarding properties of alcohol, and adolescents may be more likely to form alcohol-seeking habits that promote continued use throughout the lifetime. Therefore, we compared the development of alcohol seeking habits in adolescent and adult male, Sprague-Dawley rats. Rats were trained to lever press to receive 10% ethanol + 0.1% saccharin on a schedule that promotes habit formation. Rats were tested using a contingency degradation procedure at different points in training. Adult rats formed ethanol-seeking habits with only moderate training, while adolescents remained goal-directed even with extended training. Nevertheless, adolescents consumed more ethanol than adults throughout the experiment and continued to consume more ethanol than adults when they reached adulthood. Therefore, early onset alcohol use may promote AUD formation through establishment of high levels of drinking that becomes habitual in adulthood. PMID:25575668

  8. Cooperative Genome-Wide Analysis Shows Increased Homozygosity in Early Onset Parkinson's Disease

    PubMed Central

    Nalls, Michael A.; Martinez, Maria; Schulte, Claudia; Holmans, Peter; Gasser, Thomas; Hardy, John; Singleton, Andrew B.; Wood, Nicholas W.; Brice, Alexis; Heutink, Peter; Williams, Nigel; Morris, Huw R.

    2012-01-01

    Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity. We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort. There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis. PMID:22427796

  9. A phase II trial for the efficacy of physiotherapy intervention for early-onset hip osteoarthritis: study protocol for a randomised controlled trial.

    PubMed

    Kemp, Joanne L; Moore, Kate; Fransen, Marlene; Russell, Trevor G; Crossley, Kay M

    2015-01-27

    Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration

  10. Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity.

    PubMed

    Sibille, E; Su, J; Leman, S; Le Guisquet, A M; Ibarguen-Vargas, Y; Joeyen-Waldorf, J; Glorioso, C; Tseng, G C; Pezzone, M; Hen, R; Belzung, C

    2007-11-01

    Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-HT(1B) receptor (5-HT(1B)R), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT(1B)R (Htr1b(KO) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b(KO) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b(KO) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b(KO) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT.

  11. Bilingualism delays the onset of behavioral but not aphasic forms of frontotemporal dementia.

    PubMed

    Alladi, Suvarna; Bak, Thomas H; Shailaja, Mekala; Gollahalli, Divyaraj; Rajan, Amulya; Surampudi, Bapiraju; Hornberger, Michael; Duggirala, Vasanta; Chaudhuri, Jaydip Ray; Kaul, Subhash

    2017-05-01

    Bilingualism has been found to delay onset of dementia and this has been attributed to an advantage in executive control in bilinguals. However, the relationship between bilingualism and cognition is complex, with costs as well as benefits to language functions. To further explore the cognitive consequences of bilingualism, the study used Frontotemporal dementia (FTD) syndromes, to examine whether bilingualism modifies the age at onset of behavioral and language variants of Frontotemporal dementia (FTD) differently. Case records of 193 patients presenting with FTD (121 of them bilingual) were examined and the age at onset of the first symptoms were compared between monolinguals and bilinguals. A significant effect of bilingualism delaying the age at onset of dementia was found in behavioral variant FTD (5.7 years) but not in progressive nonfluent aphasia (0.7 years), semantic dementia (0.5 years), corticobasal syndrome (0.4 years), progressive supranuclear palsy (4.3 years) and FTD-motor neuron disease (3 years). On dividing all patients predominantly behavioral and predominantly aphasic groups, age at onset in the bilingual behavioral group (62.6) was over 6 years higher than in the monolingual patients (56.5, p=0.006), while there was no difference in the aphasic FTD group (60.9 vs. 60.6 years, p=0.851). The bilingual effect on age of bvFTD onset was shown independently of other potential confounding factors such as education, gender, occupation, and urban vs rural dwelling of subjects. To conclude, bilingualism delays the age at onset in the behavioral but not in the aphasic variants of FTD. The results are in line with similar findings based on research in stroke and with the current views of the interaction between bilingualism and cognition, pointing to advantages in executive functions and disadvantages in lexical tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

    PubMed

    Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

    2018-05-18

    Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

  13. Hyperghrelinemia in Prader-Willi Syndrome Begins in Early Infancy Long Before the Onset of Hyperphagia

    PubMed Central

    Kweh, Frederick A.; Miller, Jennifer L.; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J.; Goldstone, Anthony P.; Driscoll, Daniel J.

    2015-01-01

    Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P<0.001) higher in earlier nutritional phases: phase 1a (7,906 ± 5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P=0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. PMID:25355237

  14. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

    PubMed

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  15. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161+Th1 Cells) to CD161+Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients

    PubMed Central

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase. PMID:27123445

  16. Dysthymic disorder: clinical characteristics in relation to age at onset.

    PubMed

    Barzega, G; Maina, G; Venturello, S; Bogetto, F

    2001-09-01

    The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. The study is retrospective and enrolls a limited number of cases. The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

  17. Comparison between early and late onset breast cancer in Pakistani women undergoing breast conservative therapy: is there any difference?

    PubMed

    Bhatti, Abu Bakar Hafeez; Jamshed, Aarif; Khan, Amina; Siddiqui, Neelam; Muzaffar, Nargis; Shah, Mazhar Ali

    2014-01-01

    Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ≤ 40 and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS) . For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

  18. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  19. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies

    PubMed Central

    Chiesa, Claudio; Pacifico, Lucia; Osborn, John F.; Bonci, Enea; Hofer, Nora; Resch, Bernhard

    2015-01-01

    Abstract To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS. We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies. We found 18 articles (1998–2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing. Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS. PMID:26222858

  20. Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

    PubMed

    la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

    2013-06-01

    Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease

    PubMed Central

    Ringman, John M.; Lee, Albert S.; Juarez, Kevin O.; Mendez, Mario F.

    2012-01-01

    Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD. PMID:22460587

  2. Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease.

    PubMed

    De Roeck, Arne; Van den Bossche, Tobi; van der Zee, Julie; Verheijen, Jan; De Coster, Wouter; Van Dongen, Jasper; Dillen, Lubina; Baradaran-Heravi, Yalda; Heeman, Bavo; Sanchez-Valle, Raquel; Lladó, Albert; Nacmias, Benedetta; Sorbi, Sandro; Gelpi, Ellen; Grau-Rivera, Oriol; Gómez-Tortosa, Estrella; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Graff, Caroline; Thonberg, Håkan; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Almeida, Maria Rosário; Santana, Isabel; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; Tsolaki, Magda; Koutroumani, Maria; Matěj, Radoslav; Rohan, Zdenek; De Deyn, Peter; Engelborghs, Sebastiaan; Cras, Patrick; Van Broeckhoven, Christine; Sleegers, Kristel

    2017-09-01

    Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may

  3. Web survey of sleep problems associated with early-onset bipolar spectrum disorders.

    PubMed

    Lofthouse, Nicholas; Fristad, Mary; Splaingard, Mark; Kelleher, Kelly; Hayes, John; Resko, Susan

    2008-05-01

    As research on sleep difficulties associated with Early-Onset Bipolar Spectrum Disorders (EBSD) is limited, a web-based survey was developed to further explore these problems. 494 parents of 4-to-12 year-olds, identified by parents as being diagnosed with EBSD, completed a web survey about past and current EBSD-related sleep problems. The survey included Children's Sleep Habits Questionnaire (CSHQ) items and sleep problems from the International Classification of Sleep Disorders 2nd edition. Nearly all parents reported some type of past or current EBSD-sleep problem. Most occurred during a worst mood period, particularly with mixed manic-depressive symptoms. Symptoms caused impairments at home, school, or with peers in 96.9% of the sample and across all three contexts in 64.0% of children. Sleep problems were also noted after three-day weekends and Spring and Fall Daylight Savings time changes. Findings, study limitations, and implications for treatment and etiology are discussed.

  4. Investigating autism spectrum disorder and autistic traits in early onset eating disorder.

    PubMed

    Pooni, Jyoti; Ninteman, Aafke; Bryant-Waugh, Rachel; Nicholls, Dasha; Mandy, William

    2012-05-01

    To investigate whether young people (8-16 years) with an eating disorder have a higher prevalence of autism spectrum disorder (ASDs) and elevated autistic traits compared to typically developing (TD) peers. Twenty-two participants with early onset eating disorder (EOED) were assessed using standardized ASD measures and compared to IQ matched TD (n = 24) and ASD (n = 20) controls. An ASD diagnosis was no more common in EOED than in TD controls. However, repetitive and stereotyped behavior was more often observed in the EOED group and, compared to TD controls, there was a trend (p = .07) toward greater autistic social impairment in EOED. Whilst participants with EOED did not show increased ASD prevalence, they did have elevated autistic traits of clinical significance, particularly repetitive and stereotyped behavior. Further work is required to determine whether inflexibility and social difficulties in EOED have identical phenomenology and etiology to those seen in ASD. Copyright © 2012 Wiley Periodicals, Inc.

  5. Prospective Prediction of Juvenile Homicide/Attempted Homicide among Early-Onset Juvenile Offenders

    PubMed Central

    Baglivio, Michael T.; Wolff, Kevin T.

    2017-01-01

    While homicide perpetrated by juveniles is a relatively rare occurrence, between 2010 and 2014, approximately 7%–8% of all murders involved a juvenile offender. Unfortunately, few studies have prospectively examined the predictors of homicide offending, with none examining first-time murder among a sample of adjudicated male and female youth. The current study employed data on 5908 juvenile offenders (70% male, 45% Black) first arrested at the age of 12 or younger to prospectively examine predictors of an arrest for homicide/attempted homicide by the age of 18. Among these early-onset offenders, males, Black youth, those living in households with family members with a history of mental illness, those engaging in self-mutilation, and those with elevated levels of anger/aggression (all measured by age 13) were more likely to be arrested for homicide/attempted homicide by age 18. These findings add to the scant scientific literature on the predictors of homicide, and illustrate potential avenues for intervention. PMID:28212340

  6. Prospective Prediction of Juvenile Homicide/Attempted Homicide among Early-Onset Juvenile Offenders.

    PubMed

    Baglivio, Michael T; Wolff, Kevin T

    2017-02-16

    While homicide perpetrated by juveniles is a relatively rare occurrence, between 2010 and 2014, approximately 7%-8% of all murders involved a juvenile offender. Unfortunately, few studies have prospectively examined the predictors of homicide offending, with none examining first-time murder among a sample of adjudicated male and female youth. The current study employed data on 5908 juvenile offenders (70% male, 45% Black) first arrested at the age of 12 or younger to prospectively examine predictors of an arrest for homicide/attempted homicide by the age of 18. Among these early-onset offenders, males, Black youth, those living in households with family members with a history of mental illness, those engaging in self-mutilation, and those with elevated levels of anger/aggression (all measured by age 13) were more likely to be arrested for homicide/attempted homicide by age 18. These findings add to the scant scientific literature on the predictors of homicide, and illustrate potential avenues for intervention.

  7. Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

    PubMed

    Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

    2012-12-01

    Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Do Substance Use Risk Personality Dimensions Predict the Onset of Substance Use in Early Adolescence? A Variable- and Person-Centered Approach

    ERIC Educational Resources Information Center

    Malmberg, Monique; Kleinjan, Marloes; Vermulst, Ad A.; Overbeek, Geertjan; Monshouwer, Karin; Lammers, Jeroen; Engels, Rutger C. M. E.

    2012-01-01

    Various studies found personality to be related to substance use, but little attention is paid to the role of personality risk dimensions with regard to an early onset of alcohol, tobacco, and marijuana use. Therefore, the current study used a variable-centered approach to examine whether anxiety sensitivity, hopelessness, sensation seeking, and…

  9. Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

    PubMed

    Ensari, Arzu; Kelsen, Judith; Russo, Pierre

    2018-01-01

    Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.

  10. Brain network informed subject community detection in early-onset schizophrenia.

    PubMed

    Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W; Handwerker, Daniel A; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A

    2014-07-03

    Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

  11. Germline TP53 Mutations in Patients With Early-Onset Colorectal Cancer in the Colon Cancer Family Registry

    PubMed Central

    Yurgelun, Matthew B.; Masciari, Serena; Joshi, Victoria A.; Mercado, Rowena C.; Lindor, Noralane M.; Gallinger, Steven; Hopper, John L.; Jenkins, Mark A.; Buchanan, Daniel D.; Newcomb, Polly A.; Potter, John D.; Haile, Robert W.; Kucherlapati, Raju; Syngal, Sapna

    2015-01-01

    IMPORTANCE Li-Fraumeni syndrome, usually characterized by germline TP53 mutations, is associated with markedly elevated lifetime risks of multiple cancers, and has been linked to an increased risk of early-onset colorectal cancer. OBJECTIVE To examine the frequency of germline TP53 alterations in patients with early-onset colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter cross-sectional cohort study of individuals recruited to the Colon Cancer Family Registry (CCFR) from 1998 through 2007 (genetic testing data updated as of January 2015). Both population-based and clinic-based patients in the United States, Canada, Australia, and New Zealand were recruited to the CCFR. Demographic information, clinical history, and family history data were obtained at enrollment. Biospecimens were collected from consenting probands and families, including microsatellite instability and DNA mismatch repair immunohistochemistry results. A total of a 510 individuals diagnosed as having colorectal cancer at age 40 years or younger and lacking a known hereditary cancer syndrome were identified from the CCFR as being potentially eligible. Fifty-three participants were excluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47) or biallelic MUTYH mutations (n = 6). INTERVENTIONS Germline sequencing of the TP53 gene was performed. Identified TP53 alterations were assessed for pathogenicity using literature and international mutation database searches and in silico prediction models. MAIN OUTCOMES AND MEASURES Frequency of nonsynonymous germline TP53 alterations. RESULTS Among 457 eligible participants (314, population-based; 143, clinic-based; median age at diagnosis, 36 years [range, 15–40 years]), 6 (1.3%; 95%CI, 0.5%–2.8%) carried germline missense TP53 alterations, none of whom met clinical criteria for Li-Fraumeni syndrome. Four of the identified TP53 alterations have been previously described in the literature

  12. Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria

    PubMed Central

    Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D’Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano

    2017-01-01

    Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments. PMID:28850618

  13. Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan.

    PubMed

    Rashid, Muhammad U; Muhammad, Noor; Faisal, Saima; Amin, Asim; Hamann, Ute

    2013-06-27

    Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage. In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2). Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women.

  14. Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders.

    PubMed

    Hanssen, Manon; van der Werf, Margriet; Verkaaik, Mike; Arts, Baer; Myin-Germeys, Inez; van Os, Jim; Verhey, Frans; Köhler, Sebastian

    2015-08-01

    To compare the clinical and neurocognitive profile of early-onset (EOP, <40 years), late-onset (LOP, 40-59 years) and very-late-onset (VLOP, ≥60 years) psychosis. Cross-sectional observational study. Secondary, tertiary, and community mental health care. Patients with a DSM-IV diagnosis of non-affective psychotic disorder were included from two complementary studies (GROUP and PSITE) on genetic and environmental risk factors of psychosis in the Netherlands and Belgium. Main outcome measures were the severity of positive and negative symptoms, quality of life, and age-corrected scores on measures of general intelligence, verbal memory, attention, and executive function. One-year follow-up data were used to validate diagnoses and exclude participants with possible or probable dementia. 286 EOP (85%), 24 LOP (7%) and 28 VLOP (8%) participated. VLOP patients reported significantly more positive symptoms than EOP patients. Age-at-onset groups had similar age-corrected scores on IQ, verbal memory, attention and executive functions. A significantly better performance was found in VLOP compared with LOP on the CAMCOG total score, though scores were still within the normal range. After controlling for possible confounding, however, VLOP differed significantly on an attention accuracy task compared with LOP patients. Re-entering data for probable dementia patients (N = 4) did change the results regarding cognition outcomes. VLOP patients show more positive symptoms but do not appear to differ on neuropsychological tests from EOP and LOP when age is controlled for. This questions the idea that VLOP is the expression of underlying neurodegeneration. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Early onset of a microcystin-producing cyanobacterial bloom in an agriculturally-influenced Great Lakes tributary

    NASA Astrophysics Data System (ADS)

    McKay, Robert Michael L.; Tuttle, Taylor; Reitz, Laura A.; Bullerjahn, George S.; Cody, William R.; McDowell, Adam J.; Davis, Timothy W.

    2018-05-01

    In late May 2016, a cyanobacterial harmful algal bloom (cHAB) was detected in the Maumee River, the largest tributary to Lake Erie, the southernmost lake of the Laurentian Great Lakes system. Testing on 31 May identified Planktothrix agardhii as the dominant cyanobacterium with cell abundance exceeding 1.7×10 9 cells/L and total microcystins (MC) reaching 19 μg/L MC-LR equivalents, a level over 10-fold higher than the 2015 revised U.S. Environmental Protection Agency (EPA) national health advisory levels for drinking water exposure to adults. Low river discharge coincident with negligible precipitation through the latter half of May coincided with an 80% decline in river turbidity that likely favored bloom formation by a low-light adapted P. agardhii population. Also contributing to the cHAB were high initial nutrient loads and an increase of the river temperature from 13°C to 26°C over this same period. The bloom persisted through 5 June with microcystins exceeding 22 μg/L MC-LR equivalents at the bloom peak. By 6 June, the river had returned to its muddy character following a rain event and sampling on 7 June detected only low levels of toxin (<0.6 μg/L) at public water systems located near the bloom origin. The elevated toxin production associated with this early onset bloom was without precedent for the Maumee River and an unique attribute of the cHAB was the high proportion of potentially-toxic genotypes. Whereas Planktothrix spp. is common in lotic environments, and has been previously detected in the Maumee, blooms are not commonly reported. This early onset, microcystin-producing cHAB provided a rare opportunity to glean insights into environmental factors that promote bloom development and dominance by Planktothrix in lotic environments.

  16. Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia.

    PubMed

    Kweh, Frederick A; Miller, Jennifer L; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J; Goldstone, Anthony P; Driscoll, Daniel J

    2015-01-01

    Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P < 0.001) higher in earlier nutritional phases: phase 1a (7,906  ±  5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P = 0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. © 2014 Wiley Periodicals, Inc.

  17. The association between season of birth, age at onset, and clozapine use in schizophrenia.

    PubMed

    Kim, J S; Park, C M; Choi, J A; Park, E; Tchoe, H J; Choi, M; Suh, J K; Kim, Y H; Won, S H; Chung, Y C; Bae, K Y; Lee, S K; Park, S C; Lee, S H

    2017-11-01

    This study aimed to determine whether the rate of clozapine use, an indicator of refractoriness in schizophrenia, is associated with the season of birth and age at onset in patients with schizophrenia based on nationwide data. Patients with schizophrenia (n = 114 749) who received prescriptions for antipsychotic medication between 2008 and 2014 were retrospectively identified from the Korean National Health Insurance Service database. The study population was divided into three groups based on their age at the onset of schizophrenia (early, middle, and late onset). We assessed differences in the month of birth between patients and the general population. In addition, the cumulative clozapine use was calculated. Compared to the late-onset schizophrenia group, the early- and middle-onset groups showed a higher probability of birth during the winter season. In addition, the early-onset group showed the highest cumulative clozapine use rate. In the middle-onset group, the initiation of clozapine use was significantly earlier for patients born in winter compared to those born in summer. Our results indicate that the age at onset is an important factor in predicting the prognosis of schizophrenia patients. The season of birth also affects the prognosis, but with less robustness. Specifically, it appears that early disease onset and winter birth might be associated with poor outcomes in Korean patients with schizophrenia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

    PubMed Central

    Etain, Bruno; Mathieu, Flavie; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, S.; Kealey, Carmel; Blackwood, Douglas; Muir, Walter; Bellivier, Franc; Henry, C.; Dina, Christian; Gallina, Sophie; Gurling, H.; Malafosse, Alain; Preisig, Martin; Ferrero, François; Cichon, Sven; Schumacher, J.; Ohlraun, Stéphanie; Borrmann-Hassenbach, M.; Propping, Peter; Abou Jamra, Rami; Schulze, Thomas G.; Marusic, Andrej; Dernovsek, Mojca Z.; Giros, Bruno; Bourgeron, Thomas; Lemainque, Arnaud; Bacq, Delphine; Betard, Christine; Charon, Céline; Nöthen, Markus M.; Lathrop, Mark; Leboyer, Marion

    2006-01-01

    Summary Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (age at onset of 21 years or below). Non parametric multi-point analysis suggested eight regions of linkage with p-values <0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide p-value estimated over 10.000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increase marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non parametric linkage score increased from 3.51 to 3.83. This study is the first to use early onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families. PMID:16534504

  19. Successful Object Encoding Induces Increased Directed Connectivity in Presymptomatic Early-Onset Alzheimer’s Disease

    PubMed Central

    Ochoa, John Fredy; Alonso, Joan Francesc; Duque, Jon Edinson; Tobón, Carlos Andrés; Mañanas, Miguel Angel; Lopera, Francisco; Hernández, Alher Mauricio

    2016-01-01

    Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD. PMID:27792014

  20. Detorsion night-time bracing for the treatment of early onset idiopathic scoliosis.

    PubMed

    Moreau, S; Lonjon, G; Mazda, K; Ilharreborde, B

    2014-12-01

    Management for early onset scoliosis has recently changed, with the development of new surgical procedures. However, multiple surgeries are often required and high complication rates are still reported. Conservative management remains an alternative, serial casting achieving excellent results in young children. Better compliance and improvement over natural history have been reported with night-time bracing in adolescent idiopathic scoliosis (AIS), but this treatment has never been reported in early onset idiopathic scoliosis (EIOS). All patients treated for progressive EOIS by detorsion night-time bracing (DNB), and meeting the Scoliosis Research Society (SRS) criteria for brace studies were reviewed. Recommendations were given to wear the DNB 8h/night and no restriction was given regarding sports activities. Radiological parameters were compared between referral and latest follow-up. Based on the SRS criteria defined for AIS, a similar classification was used as follows to analyze the course of the curves: success group: patients with a progression of 5° or less; unsuccess group (progression or failure): patients with a progression>5°, patients with curves exceeding 45° at maturity, or who have had recommendation for/undergone surgery, or patients who changed orthopaedic treatment, or who were lost to follow-up. Thirty-three patients were included (21 girls and 12 boys), with a median Cobb angle of 31° (Q1-Q3: 22-40). Age at brace initiation averaged 50months (Q1-Q3: 25-60). Median follow-up was 102-months (Q1-Q3: 63-125). Fifteen patients (45.5%) had reached skeletal maturity at last follow-up. The success rate was 67% (22 patients), with a median Cobb angle reduction of 15° (P<0.001). Four patients stopped DNB due to an important regression. Eleven patients were in the unsuccessful group (33%). Only one had surgery. All patients remained balanced in the frontal plane and normokyphotic. Initial curve magnitude and age at brace initiation appeared to be