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  1. Loeys-Dietz Syndrome

    MedlinePlus

    ... syndrome is a genetic disorder of the body’s connective tissue. It has some features in common with Marfan ... a mutation, growth and development of the body’s connective tissue and other body systems is disrupted, leading to ...

  2. Phenotypic variability and diffuse arterial lesions in a family with Loeys-Dietz syndrome type 4.

    PubMed

    Mazzella, J-M; Frank, M; Collignon, P; Langeois, M; Legrand, A; Jeunemaitre, X; Albuisson, J

    2017-03-01

    Syndromic thoracic aortic aneurysm and dissection (TAAD) can suggest Marfan, vascular Ehlers-Danlos or Loeys-Dietz (LDS) syndromes. Several of the TGFβ-pathway-related genes predispose to different types of LDS. Heterozygous loss-of-function variations in TGFβ2 have been shown to be responsible for a novel form of syndromic TAAD associated with an impairment of the mitral valve and cerebrovascular disease called Loeys-Dietz syndrome type 4 (LDS4). We report the clinical characterization of a LDS4 French family with sudden deaths and diffuse vascular lesions, caused by a frameshift mutation in TGFβ2 gene: c.[995del]; p.(Leu332TrpfsTer27). Clinical characteristics include aneurysm of aortic sinus, skeletal and cutaneous features compatible with a syndromic form of TAAD (joint hypermobility, scoliosis, and easy bruises), intracranial aneurysms and rare mitral valve involvement. Iliac aneurysms, systemic medium caliber arteries dissections, and mild developmental delay were present in the family, and have not been described in LDS4. Phenotypic variability was also an important finding, including absence of clinical vascular events at advanced age in one case. Our data expand the phenotype of LDS4: we confirm that TGFβ2 mutations are responsible for true LDS syndrome with non-specific features of connective tissue disorders and diffuse vascular lesions. Adapted vascular follow up and prevention has to be proposed for these patients.

  3. Loeys-Dietz syndrome: life threatening aortic dissection diagnosed on routine family screening

    PubMed Central

    Martin, Claire A; Clowes, Virginia E; Cooper, John P

    2014-01-01

    A 52-year-old man was found to have a severely dilated aortic root and a Stanford type A dissection on familial screening echocardiography, following diagnosis of a dilated aorta in his son. The dissection required urgent surgical repair. Clinical examination suggested features of Loeys-Dietz syndrome type II, and subsequent demonstration of a mutation in the TGFBR1 gene in the patient and his son confirmed the diagnosis. This article highlights the high prevalence of inherited conditions in dilated aortic root presentations and the importance of family screening and surveillance to allow early surgical intervention. PMID:24495977

  4. High Prevalence of Cervical Deformity and Instability Requires Surveillance in Loeys-Dietz Syndrome

    PubMed Central

    Fuhrhop, Sara K.; McElroy, Mark J.; Dietz, Harry C.; MacCarrick, Gretchen L.; Sponseller, Paul D.

    2015-01-01

    Background: Loeys-Dietz syndrome is a connective tissue disorder characterized by vascular, craniofacial, and musculoskeletal malformation. Our goal was to report the manifestations, surgical treatment, and complications in the cervical spine in patients with Loeys-Dietz syndrome. Methods: We reviewed the clinical and cervical spine imaging data of eighty patients with Loeys-Dietz syndrome who were seen at our institution from January 2005 through January 2014. Their mean age at presentation was 17.3 years (range, three months to seventy-five years). We tested associations with use of the Fisher exact test (type of TGF-βR [transforming growth factor-beta receptor] mutation and cervical abnormalities) and the Student t test (age at presentation and type of TGF-βR mutation) (significance, p = 0.05). Results: Vertebral anomalies and cervical instability were common; we found no significant association of TGF-βR-type with cervical abnormalities or age at presentation. Twenty-eight patients had atlas defects (anterior and/or posterior arch defects or hypoplasia), fifty-three had axis malformations (elongation, apex-anterior dens angulation, or spondylolysis), and twelve had focal kyphosis. Ten patients had hypoplastic subaxial vertebrae, leading to focal kyphosis (eight) and subaxial instability (nine). Eight patients had atlantoaxial instability. Of the thirteen patients with cervical instability, nine were treated surgically: fusion (eight patients) and halo application (one) (mean age, four years; range, three months to twelve years). Postoperative complications (seven patients) were pseudarthrosis, failure of fixation, junctional kyphosis or instability, and development of occipital-cervical instability. Conclusions: Cervical midline defects (most often C1-C3) are common in Loeys-Dietz syndrome. Patients have a high prevalence of cervical instability, particularly a pattern of instability at C2-C3 associated with C3 vertebral body hypoplasia and C2-C3 focal

  5. Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation

    PubMed Central

    2014-01-01

    Background The Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder characterized by thoracic aortic aneurysm and dissection and widespread systemic connective tissue involvement. LDS type 1 to 4 are caused by mutations in genes of the TGF-β signaling pathway: TGFBR1 and TGFBR2 encoding the TGF-β receptor (LDS1 and LDS2), SMAD3 encoding the TGF-β receptor cytoplasmic effector (LDS3), and TGFB2 encoding the TGF-β2 ligand (LDS4). LDS4 represents the mildest end of the LDS spectrum, since aneurysms are usually observed in fourth decade and the progression of the disease is slower than in the other forms. Case presentation We report the clinical and molecular findings of an LDS4 Italian family. Genetic testing included TGFBR1, TGFBR2, SMAD3, and TGFB2 analysis by Sanger sequencing. In order to verify the effect of the identified splice mutation, RT-PCR analysis was performed. The proband, a 57-year-old woman, showed high palate, hypoplasic uvula, easy bruising, joint hypermobility, chronic pain, scoliosis, multiple relapsing hernias, dural ectasia, and mitral valve prolapse. Magnetic resonance angiography revealed tortuosity and ectasia of carotid, vertebral, cerebral, and segmental pulmonary arteries. Arterial aneurysm and dissection never occurred. Her 39- and 34-year-old daughters presented with a variable degree of musculoskeletal involvement. Molecular analysis disclosed the novel c.839-1G>A splice site mutation in the TGFB2 gene. This mutation activates a cryptic splice acceptor site in exon 6 leading to frameshift, premature termination codon and haploinsufficiency (p.Gly280Aspfs*41). Conclusions Our data confirm that loss-of-function mutations in TGFB2 gene do not always lead to aggressive vascular phenotypes and that articular and skeletal signs are prevalent, therefore suggesting that LDS4 must be considered in patients with sparse signs of LDS and related disorders also in the absence of vascular events. PMID:25163805

  6. Aortic and Pulmonary Root Aneurysms in a Child With Loeys-Dietz Syndrome.

    PubMed

    Rizzo, Stefania; Stellin, Giovanni; Milanesi, Ornella; Padalino, Massimo; Vricella, Luca A; Thiene, Gaetano; Cameron, Duke E; Basso, Cristina; Vida, Vladimiro L

    2016-03-01

    We report the case of an 11-year-old boy with Loeys-Dietz syndrome, with both aortic and pulmonary aneurysms requiring cardiac operation because of progressive valve incompetence resulting from loss of coaptation of the cusps. Arterial medial changes, consisting of disarray of elastic fibers and increased collagen deposition, were observed in surgical specimens from both the aorta and the pulmonary artery of our patient, and the strong pSmad2 nuclear staining of smooth muscle cells of both aortic and pulmonary tunica media are the best evidence of transforming growth factor-β pathway activation in Loeys-Dietz syndrome.

  7. Increased fracture risk and low bone mineral density in patients with loeys-dietz syndrome.

    PubMed

    Tan, Eric W; Offoha, Roosevelt U; Oswald, Gretchen L; Skolasky, Richard L; Dewan, Ashvin K; Zhen, Gehua; Shapiro, Jay R; Dietz, Harry C; Cao, Xu; Sponseller, Paul D

    2013-08-01

    Loeys-Dietz syndrome is a recently recognized connective tissue disorder with widespread systemic involvement. Little is known about its skeletal phenotype. Our goal was to investigate the risk of fracture and incidence of low bone mineral density in patients with Loeys-Dietz syndrome. We performed a cross-sectional, descriptive, survey-based study with subsequent chart review from July 2011 to April 2012. Fifty-seven patients (26 men, 31 women) with Loeys-Dietz syndrome confirmed by genetic testing completed the survey (average age, 25.3 years; range, 0.9-79.6 years). There were a total of 51 fractures (33 patients): 35 fractures in the upper extremities, 14 in the lower extremities, and two in the spine. Fourteen patients (24.6%) reported two or more fractures. There was a 50% risk of fracture by age 14 years. The incidence of any fracture in this cohort was 3.86 per 100 person-years. Seventeen patients had dual-energy X-ray absorptiometry scans available for review, 11 (64.7%) of whom had at least one fracture. Thirteen included lumbar spine absorptiometry reports; eight (61.5%) indicated low or very low bone mineral density. In the left hip, ten of 14 participants (71.4%) had low or very low bone mineral density. In the left femoral neck, nine of 13 participants (69.2%) had low or very low bone mineral density. The lowest Z- and T-scores were not associated with an increased number of fractures. Patients with Loeys-Dietz syndrome have a high risk of fracture and a high incidence of low bone mineral density.

  8. Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations.

    PubMed

    Söylen, B; Singh, K K; Abuzainin, A; Rommel, K; Becker, H; Arslan-Kirchner, M; Schmidtke, J

    2009-03-01

    Marfan syndrome is an autosomal dominant disorder involving different organ systems. Marfan syndrome type 1 (MFS1) is caused by mutations in the FBN1 gene. Heterozygosity for mutations in the TGFBR1 or TGFBR2 genes cause Loeys-Dietz syndrome (LDS) types 2A and 2B that overlap with MFS1 in their clinical features. The phenotype of MFS1 is defined by the Ghent nosology, which classifies the clinical manifestations in major and minor criteria. Dural ectasia is one of the major criteria for Marfan syndrome but it is rarely tested for. We here report 22 novel and 9 recurrent mutations in the FBN1 gene in 36 patients with clinical features of Marfan syndrome. Sixty patients with identified mutations in the FBN1 gene and three patients with mutations in the TGFBR1 or TGFBR2 genes were examined for dural ectasia. Forty-seven of the 60 patients (78%) with MFS1 showed the dural ectasia criterion and 13 (22%) did not. Thirty-three (55%) patients were suspected of having Marfan syndrome and 24 (73%) of them had dural ectasia. Two of the three patients with LDS had dural ectasia.

  9. Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys-Dietz Syndromes.

    PubMed

    Takeda, Norifumi; Yagi, Hiroki; Hara, Hironori; Fujiwara, Takayuki; Fujita, Daishi; Nawata, Kan; Inuzuka, Ryo; Taniguchi, Yuki; Harada, Mutsuo; Toko, Haruhiro; Akazawa, Hiroshi; Komuro, Issei

    2016-05-25

    Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management.

  10. A patient with Loeys-Dietz syndrome treated with chemoradiotherapy for an oropharyngeal carcinoma.

    PubMed

    Chan, Andrew K; Teoh, Daren; Matthews, Paul; Fresco, Lydia

    2013-09-17

    We present the first published case of a patient with Loeys-Dietz syndrome (LDS) who was treated with radical chemoradiotherapy for an oropharyngeal carcinoma. In view of this newly recognised connective tissue disease, the uncertainty of severe toxicity from chemoradiotherapy to treat a potentially curative cancer posed a management challenge. The patient was treated with chemoradiotherapy and remains well with no evidence of recurrence at 3 years. Furthermore, we have observed minimal late effects secondary to chemoradiotherapy at 3 years following the completion of treatment suggesting that the underlying pathogenesis of LDS may provide an interesting human model to further elucidate the complex interactions of transforming growth factor β1 (TGF-β1) and tissue fibrosis secondary to chemoradiotherapy. A review of LDS as well as the association of TGF-β1 expression and tissue fibrosis is presented.

  11. Valve-sparing replacement of the ascending aorta and aortic arch in a child with Loeys-Dietz syndrome.

    PubMed

    Ozker, Emre; Vuran, Can; Saritas, Bülent; Türköz, Riza

    2012-05-01

    We describe a successful surgical treatment in a 2.5-year old boy with Loeys-Dietz syndrome, in whom we performed aortic arch and ascending aorta replacement with a valve-sparing operation (VSO) of the aortic root because of significant aortic insufficiency and dilation of the aortic root. We believe that VSO is ideal for treating young patients with aortic root aneurysm with normal or minimally diseased aortic cusps to avoid the disadvantages of prosthetic valve replacements.

  12. Detection of 15 novel mutations in 52 children from 40 families with the Marfan or Loeys-Dietz syndrome and phenotype-genotype correlations.

    PubMed

    Pees, C; Michel-Behnke, I; Hagl, M; Laccone, F

    2014-12-01

    We report about 52 pediatric patients of 40 different families with confirmed Marfan syndrome (MFS) in 49 patients and Loeys-Dietz syndrome (LDS) in 3 patients. We found 39 different mutations, 15 of them being novel. Phenotype-genotype correlation in the 49 MFS patients showed that the majority of patients carrying mutations in exons 1-21 had ectopic lens (80%). Patients having mutations in exons 23-32 had a higher probability of aortic root dilation, in 50% even above a z score of 3. We found three children with neonatal MFS form, two of them with novel mutations. Of the three LDS patients, only one presented with the typical phenotype of LDS type 1.

  13. Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome

    PubMed Central

    Zimmermann, Michael T.; Urrutia, Raul A.; Blackburn, Patrick R.; Cousin, Margot A.; Boczek, Nicole J.; Klee, Eric W.; Macmurdo, Colleen

    2017-01-01

    Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular findings of aneurysm and/or dissection of cerebral, thoracic, or abdominal arteries and skeletal findings. We report a case of a novel pathogenic variant in TGFBR2 and phenotype consistent with classic LDS. The proband was a 10-year-old presenting to the genetics clinic with an enlarged aortic root (Z-scores 5-6), pectus excavatum, and congenital contractures of the right 2nd and 3rd digit. Molecular testing of TGFBR2 was sent to a commercial laboratory and demonstrated a novel, likely pathogenic, variant in exon 4, c.1061T>C, p.(L354P). Molecular modeling reveals alteration of local protein structure as a result of this pathogenic variant. This pathogenic variant has not been previously reported in LDS and thus expands the pathogenic variant spectrum of this condition. PMID:28163941

  14. Early Diagnosis and Repair of Double Saccular Aneurysms of the Aortic Arch Associated With Aortic Coarctation in an Infant With Loeys-Dietz Syndrome.

    PubMed

    Ilyin, Vladimir N; Kornoukhov, O Ju; Khovrin, Valery V; Kryukov, Vladislav A; Valitova, Asia A; Ilina, Maria V

    2016-03-01

    Multiple saccular aneurysms of the thoracic aorta in neonates and infants are exceedingly rare. An association of these aneurysms with Loeys-Dietz syndrome (LDS) in older age-groups is well known. This case report describes the diagnosis and subsequent successful repair of aortic coarctation associated with double saccular aneurysms of the thoracic aorta in patient with LDS during the first year of life.

  15. Genetics Home Reference: Loeys-Dietz syndrome

    MedlinePlus

    ... Diagnosis & Management Formal Diagnostic Criteria (1 link) Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, ... M, Rousseau H, Sechtem U, Sirnes PA, Allmen RS, Vrints CJ; ESC Committee for Practice Guidelines. 2014 ...

  16. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

    PubMed

    Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes.

  17. What Are Related Disorders?

    MedlinePlus

    ... physical problems. Some examples are Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and Familial Thoracic Aortic Aneurysm and Dissection. ... are related to Marfan syndrome: Loeys-Dietz Syndrome Ehlers-Danlos Syndrome Familial Thoracic Aortic Aneurysm and Dissection MASS ...

  18. De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and a clinical review.

    PubMed

    Au, P Y Billie; Racher, Hilary E; Graham, John M; Kramer, Nancy; Lowry, R Brian; Parboosingh, Jillian S; Innes, A Micheil

    2014-03-01

    Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder characterized by craniosynostosis, distinctive craniofacial features, skeletal abnormalities, marfanoid body habitus, aortic dilatation, and intellectual disability. Mutations in exon 1 of SKI have recently been identified as being responsible for approximately 90% of reported individuals diagnosed clinically with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFβ signaling. Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome is likely caused by deregulated TGFβ signals, explaining the considerable phenotypic overlap between these three disorders. We describe two additional patients with exon 1 SKI mutations and review the clinical features and literature of Shprintzen-Goldberg syndrome.

  19. Analysis of TGFBR1*6A variant in individuals evaluated for Marfan syndrome.

    PubMed

    Somers, Allyson E; Hinton, Robert B; Pilipenko, Valentina; Miller, Erin; Ware, Stephanie M

    2016-07-01

    Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are genetic disorders that affect connective tissue as a result of dysregulated TGF-β signaling. MFS is most frequently caused by mutations in FBN1 whereas Loeys-Dietz syndrome results from mutations in TGFBR1 or TGFBR2. There is substantial inter- and intra-familial phenotypic variability among these disorders, suggesting the presence of genetic modifiers. Previously, a polymorphism in the TGFβR1 protein termed the TFGBR1*6A allele was found to be overrepresented in patients with MFS and was identified as a low penetrance allele with suggestion as a possible modifier. To further investigate the importance of this variant, a retrospective review of genetic and phenotypic findings was conducted for 335 patients evaluated for suspicion of MFS or related disorders. In patients with a diagnosis of MFS, the presence of the TFGBR1*6A allele was not associated with phenotypic differences. Similarly, careful phenotyping of patients who carried the TFGBR1*6A allele but did not have MFS did not identify an altered frequency of specific connective tissue features. In this small cohort, the results did not reach significance to identify the TFGBR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. © 2016 Wiley Periodicals, Inc.

  20. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    PubMed Central

    Cury, Marcelo; Zeidan, Fernanda; Lobato, Armando C.

    2013-01-01

    There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research. PMID:23401778

  1. Development of a Novel Treatment for Food Allergy Using a New Genetically Defined Mouse Model of the Disease

    DTIC Science & Technology

    2012-07-01

    13. SUPPLEMENTARY NOTES 14. ABSTRACT Loeys Dietz Syndrome (LDS) is an autosomal dominant disorder caused by mutations in the...development of these disorders , frustrating efforts to develop mechanism-based therapies. Loeys-Dietz Syndrome (LDS), a recently described autosomal...dominant disorder caused by mutations in either of the two genes encoding subunits of the TGFbeta receptor (TGFBR1 or TGFBR2), is the first

  2. Cardiovascular manifestations in Marfan syndrome and related diseases; multiple genes causing similar phenotypes.

    PubMed

    Cook, J R; Carta, L; Galatioto, J; Ramirez, F

    2015-01-01

    Cardiovascular abnormalities are the major cause of morbidity and mortality in Marfan syndrome (MFS) and a few clinically related diseases that share, with MFS, the pathogenic contribution of dysregulated transforming growth factor β (TGFβ) signaling. They include Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome, aneurysm-osteoarthritis syndrome and syndromic thoracic aortic aneurysms. Unlike the causal association of MFS with mutations in an extracellular matrix protein (ECM), the aforementioned conditions are due to defects in components of the TGFβ pathway. While TGFβ antagonism is being considered as a potential new therapy for these heritable syndromes, several points still need to be clarified in relevant animal models before this strategy could be safely applied to patients. Among others, unresolved issues include whether elevated TGFβ signaling is responsible for all MFS manifestations and is the common trigger of disease in MFS and related conditions. The scope of our review is to highlight the clinical and experimental findings that have forged our understanding of the natural history and molecular pathogenesis of cardiovascular manifestations in this group of syndromic conditions.

  3. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.

    PubMed

    Doyle, Alexander J; Doyle, Jefferson J; Bessling, Seneca L; Maragh, Samantha; Lindsay, Mark E; Schepers, Dorien; Gillis, Elisabeth; Mortier, Geert; Homfray, Tessa; Sauls, Kimberly; Norris, Russell A; Huso, Nicholas D; Leahy, Dan; Mohr, David W; Caulfield, Mark J; Scott, Alan F; Destrée, Anne; Hennekam, Raoul C; Arn, Pamela H; Curry, Cynthia J; Van Laer, Lut; McCallion, Andrew S; Loeys, Bart L; Dietz, Harry C

    2012-11-01

    Elevated transforming growth factor (TGF)-β signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-β signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-β signaling cascades and higher expression of TGF-β-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-β signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.

  4. The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen-Goldberg syndrome.

    PubMed

    Schepers, Dorien; Doyle, Alexander J; Oswald, Gretchen; Sparks, Elizabeth; Myers, Loretha; Willems, Patrick J; Mansour, Sahar; Simpson, Michael A; Frysira, Helena; Maat-Kievit, Anneke; Van Minkelen, Rick; Hoogeboom, Jeanette M; Mortier, Geert R; Titheradge, Hannah; Brueton, Louise; Starr, Lois; Stark, Zornitza; Ockeloen, Charlotte; Lourenco, Charles Marques; Blair, Ed; Hobson, Emma; Hurst, Jane; Maystadt, Isabelle; Destrée, Anne; Girisha, Katta M; Miller, Michelle; Dietz, Harry C; Loeys, Bart; Van Laer, Lut

    2015-02-01

    Shprintzen-Goldberg syndrome (SGS) is a rare, systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations that show a significant overlap with the features observed in the Marfan (MFS) and Loeys-Dietz syndrome (LDS). A distinguishing observation in SGS patients is the presence of intellectual disability, although not all patients in this series present this finding. Recently, SGS was shown to be due to mutations in the SKI gene, encoding the oncoprotein SKI, a repressor of TGFβ activity. Here, we report eight recurrent and three novel SKI mutations in eleven SGS patients. All were heterozygous missense mutations located in the R-SMAD binding domain, except for one novel in-frame deletion affecting the DHD domain. Adding our new findings to the existing data clearly reveals a mutational hotspot, with 73% (24 out of 33) of the hitherto described unrelated patients having mutations in a stretch of five SKI residues (from p.(Ser31) to p.(Pro35)). This implicates that the initial molecular testing could be focused on mutation analysis of the first half of exon 1 of SKI. As the majority of the known mutations are located in the R-SMAD binding domain of SKI, our study further emphasizes the importance of TGFβ signaling in the pathogenesis of SGS.

  5. Differential Diagnosis of Genetic Disorders Associated with Moderate to Severe Refractory Eczema and Elevated Immunoglobulin E.

    PubMed

    Arjona Aguilera, C; Albarrán Planelles, C; Tercedor Sánchez, J

    2016-03-01

    The association of moderate to severe eczema and elevated plasma levels of immunoglobulin E is a characteristic not only of atopic dermatitis but also of various genodermatoses: hyperimmunoglobulin E syndromes, Omenn syndrome, Netherton syndrome, peeling skin syndrome type B, severe dermatitis, multiple allergies, and metabolic wasting syndrome, Wiskott-Aldrich syndrome, prolidase deficiency, Loeys-Dietz syndrome, IPEX syndrome, STAT5B deficiency, and pentasomy X. The clinical presentation of these genodermatoses -typically in children- is consistent with severe atopic dermatitis. Immunoglobulin E is elevated from birth and response to conventional treatments is poor. Diagnosis is further complicated by the fact that these genodermatoses often share other clinical manifestations and laboratory findings. We present practical guidelines for differentiating among these various entities, with the aim of helping physicians decide what type of genetic test should be carried out -and when- in order to establish a definitive diagnosis.

  6. Genes Predisposing to Thoracic Aortic Aneurysms and Dissections: Associated Phenotypes, Gene-Specific Management, and Genetic Testing

    PubMed Central

    Milewicz, Dianna M.; Carlson, Alicia A.; Regalado, Ellen S.

    2011-01-01

    Thoracic aortic aneurysms leading to type A dissections (TAAD) are the major diseases affecting the aorta. A genetic predisposition for TAAD can occur as part of a genetic syndrome, as is the case for Marfan syndrome, due to mutations in FBN1, and Loeys-Dietz syndrome, which results from mutations in either TGFBR1 or TGFBR2. A predisposition to TAAD in the absence of syndromic features can be inherited in an autosomal dominant manner with decreased penetrance and variable expression, termed familial TAAD. Familial TAAD exhibits clinical and genetic heterogeneity. Genetic heterogeneity for familial TAAD has been demonstrated by the identification of four genes leading to TAAD, including TGFBR2 and TGFBR1, MYH11, and ACTA2. The phenotype and management of patients harboring mutations in these genes, along with genetic testing, will be addressed in this review. PMID:20452526

  7. Griscelli syndrome type-3

    PubMed Central

    Shah, Bela J.; Jagati, Ashish K.; Katrodiya, Nilesh K.; Patel, Sonal M.

    2016-01-01

    Griscelli syndrome (GS) is a rare autosomal recessive multisystem disorder of pigmentary dilution of skin, silver gray hair, variable immunodeficiency, neurological impairment, and abnormal accumulation of melanosomes in melanocytes. GS type 3 is characterized by hypomelanosis with no immunological and neurological manifestation. Prognosis is very good in type 3 GS and usually require no active intervention, as opposed to type 1 and 2 where early diagnosis and treatment plays a crucial role in patient's survival. The characteristic phenotypic appearance, especially the pigment dilution of the patient's hair, is emphasized here. PMID:27990386

  8. Modified pediatric Bentall procedure: A novel technique in a rare case

    PubMed Central

    Salve, Gananjay G; Javali, Satish R; Dalvi, Bharat V; Krishnanaik, Shivaprakash

    2016-01-01

    Aneurysms of ascending aorta are rarely seen in pediatric age group. Only few cases with Marfans syndrome have been reported in the literature. Preferred treatment for these children has been the standard Bentall procedure (aortic root replacement with composite graft prosthesis). We report a 4-year-old male child with huge aneurysm of ascending aorta and aortic root dilation with severe aortic regurgitation, having phenotypic features of Loeys-Dietz syndrome type I. He underwent Bentall procedure with a novel modification (medial trap-door technique for coronary reimplantation). Short-term result of this procedure is encouraging and he is asymptomatic for the last 14 months of follow-up. PMID:27625523

  9. Type 4 cardiorenal syndrome.

    PubMed

    Pinheiro da Silva, Ana Luísa; Vaz da Silva, Manuel Joaquim

    2016-11-01

    The Acute Dialysis Quality Initiative consensus conference proposed a classification of cardiorenal syndrome (CRS), aiming for a better delineation of each subtype. Although the exact pathophysiology of type 4 CRS is not completely understood, the mechanisms involved are probably multifactorial. There is growing evidence that oxidative stress is a major connector in the development and progression of type 4 CRS. Giving its complexity, poor prognosis and increasing incidence, type 4 CRS is becoming a significant public health problem. Patients with chronic kidney disease are particularly predisposed to cardiac dysfunction, due to the high prevalence of traditional cardiovascular risk factors in this population, but the contribution of risk factors specific to chronic kidney disease should also be taken into account. Much remains to be elucidated about type 4 CRS: despite progress over the last decade, there are still significant questions regarding its pathophysiology and there is as yet no specific therapy. A better understanding of the mechanisms involved may provide potential targets for intervention. The present review will provide a brief description of the definition, epidemiology, diagnosis, prognosis, biomarkers and management strategies of type 4 CRS, and the pathophysiological mechanisms and risk factors presumably involved in its development will be particularly highlighted.

  10. National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions

    ClinicalTrials.gov

    2016-12-19

    Marfan Syndrome; Turner Syndrome; Ehlers-Danlos Syndrome; Loeys-Dietz Syndrome; FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation; Bicuspid Aortic Valve Without Known Family History; Bicuspid Aortic Valve With Family History; Bicuspid Aortic Valve With Coarctation; Familial Thoracic Aortic Aneurysm and Dissections; Shprintzen-Goldberg Syndrome; Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo; Other Congenital Heart Disease

  11. Genetics Home Reference: otopalatodigital syndrome type 2

    MedlinePlus

    ... Conditions otopalatodigital syndrome type 2 otopalatodigital syndrome type 2 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Otopalatodigital syndrome type 2 is a disorder involving abnormalities in skeletal development ...

  12. Types of Myelodysplastic Syndromes

    MedlinePlus

    ... the bone marrow have at least one certain chromosome abnormality that is only seen in MDS or leukemia. The number of blasts in the bone marrow is less than 5%. Because this type ... this type of MDS, the chromosomes of the bone marrow cells are normal except ...

  13. Ehlers-Danlos Syndrome Hypermobility Type

    MedlinePlus

    ... should be considered with caution What is the life expectancy of someone with Ehlers-Danlos syndrome hypermobility type? Ehlers-Danlos syndrome hypermobility type does not affect life expectancy. Do you have questions? Would you like more ...

  14. Genetic Risk for Aortic Aneurysm in Adolescent Idiopathic Scoliosis

    PubMed Central

    Haller, Gabe; Alvarado, David M.; Willing, Marcia C.; Braverman, Alan C.; Bridwell, Keith H.; Kelly, Michael; Lenke, Lawrence G.; Luhmann, Scott J.; Gurnett, Christina A.; Dobbs, Matthew B.

    2015-01-01

    Background: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. Methods: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. Results: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. Conclusions: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. Clinical

  15. ADPKD: Prototype of Cardiorenal Syndrome Type 4

    PubMed Central

    Virzì, Grazia Maria; Corradi, Valentina; Panagiotou, Anthi; Gastaldon, Fiorella; Cruz, Dinna N.; de Cal, Massimo; Clementi, Maurizio; Ronco, Claudio

    2011-01-01

    The cardiorenal syndrome type 4 (Chronic Renocardiac Syndrome) is characterized by a condition of primary chronic kidney disease (CKD) that leads to an impairment of the cardiac function, ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. Clinically, it is very difficult to distinguish between CRS type 2 (Chronic Cardiorenal Syndrome) and CRS type 4 (Chronic Renocardiac Syndrome) because often it is not clear whether the primary cause of the syndrome depends on the heart or the kidney. Autosomal dominant polycystic kidney disease (ADPKD), a genetic disease that causes CKD, could be viewed as an ideal prototype of CRS type 4 because it is certain that the primary cause of cardiorenal syndrome is the kidney disease. In this paper, we will briefly review the epidemiology of ADPKD, conventional and novel biomarkers which may be useful in following the disease process, and prevention and treatment strategies. PMID:21234092

  16. Genetics Home Reference: otopalatodigital syndrome type 1

    MedlinePlus

    ... of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2 , ... 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic ...

  17. Prenatal diagnosis of type 2 Pfeiffer syndrome.

    PubMed

    Bernstein, P S; Gross, S J; Cohen, D J; Tiller, G R; Shanske, A L; Bombard, A T; Marion, R W

    1996-12-01

    Pfeiffer syndrome is an autosomal dominantly inherited disorder consisting of craniosynostosis, a flattened midface with a beaked nose and ocular proptosis, and broad and medially deviated thumbs and great toes. Recently, based on clinical findings, the disorder has been divided into three subtypes: type 1, characterized by mild expression; type 2, in which clover leaf skull deformity and multiple congenital anomalies are present at birth; and type 3, which is similar to type 2, but lacks the presence of the clover leaf skull at birth. We describe a fetus in whom sonographic findings of clover leaf skull deformity, ocular hypertelorism, and varus deformity of the great toe led to the prenatal diagnosis of Pfeiffer syndrome type 2. We believe this is the second prenatal diagnosis of Pfeiffer syndrome, and the first time type 2 has been definitely identified in the second trimester of pregnancy.

  18. Genetic heterogeneity of Usher syndrome type II.

    PubMed Central

    Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

    1993-01-01

    Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

  19. Prenatal diagnosis of Pfeiffer syndrome type II.

    PubMed

    Blaumeiser, Bettina; Loquet, Philip; Wuyts, Wim; Nöthen, Markus M

    2004-08-01

    Pfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history.

  20. Fluconazole-Induced Type 1 Kounis Syndrome.

    PubMed

    Singh Mahal, Hardeep

    2016-01-01

    The administration of fluconazole is commonly used in both inpatient and outpatient settings for the management of candidiasis infection. Although it is associated with a relatively safe side effect profile, some patients experience adverse effects associated with increased morbidity. We describe 1 such patient, a 42-year-old woman with a history of severe eczema who developed fluconazole-induced type 1 Kounis syndrome. Review of literature indicates that this as the first case reported of fluconazole-induced type 1 Kounis syndrome.

  1. Moyamoya syndrome and neurofibromatosis type 1

    PubMed Central

    2014-01-01

    Neurofibromatosis type 1 (NF1) is the most prevalent autosomal dominant genetic disorder among humans. NF1 vasculopathy is a significant but underrecognized complication of the disease, affecting both arterial and venous blood vessels of all sizes. Moyamoya syndrome is a cerebral vasculopathy that is only rarely observed in association with NF1, particularly in the pediatric age range. Herein, we report of a 5-year-old female with NF1 and moyamoya syndrome and we briefly review the existing literature. PMID:24952383

  2. Absence of Cardiovascular Manifestations in a Haploinsufficient Tgfbr1 Mouse Model

    PubMed Central

    Renard, Marjolijn; Trachet, Bram; Casteleyn, Christophe; Campens, Laurence; Cornillie, Pieter; Callewaert, Bert; Deleye, Steven; Vandeghinste, Bert; van Heijningen, Paula M.; Dietz, Harry; De Vos, Filip; Essers, Jeroen; Staelens, Steven; Segers, Patrick; Loeys, Bart; Coucke, Paul; De Paepe, Anne; De Backer, Julie

    2014-01-01

    Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor β (TGFβ)-associated vasculopathies. In its most typical form it is characterized by the presence of hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial tortuosity. LDS is caused by heterozygous loss of function mutations in the genes encoding TGFβ receptor 1 and 2 (TGFBR1 and −2), which lead to a paradoxical increase in TGFβ signaling. To address this apparent paradox and to gain more insight into the pathophysiology of aneurysmal disease, we characterized a new Tgfbr1 mouse model carrying a p.Y378* nonsense mutation. Study of the natural history in this model showed that homozygous mutant mice die during embryonic development due to defective vascularization. Heterozygous mutant mice aged 6 and 12 months were morphologically and (immuno)histochemically indistinguishable from wild-type mice. We show that the mutant allele is degraded by nonsense mediated mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since this haploinsufficiency model does not result in cardiovascular malformations, it does not allow further study of the process of aneurysm formation. In addition to providing a comprehensive method for cardiovascular phenotyping in mice, the results of this study confirm that haploinsuffciency is not the underlying genetic mechanism in human LDS. PMID:24587008

  3. Bartter's syndrome with type 2 diabetes mellitus.

    PubMed

    See, Ting-Ting; Lee, Siu-Pak

    2009-02-01

    We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.

  4. Waardenburg Syndrome type 1: A case report.

    PubMed

    Demirci, Gulsen Tukenmez; Atıs, Guldehan; Altunay, Ilknur Kıvanc

    2011-11-15

    Waardenburg Syndrome (WS) is a rare hereditary disorder that is characterized by the clinical manifestations of oculocutaneous anomalies of pigmentation, congenital deafness, dystopia canthorum, and broad nasal root. It demonstrates both genetically and clinically heterogenous characteristics. In this article, we report an 11-month-old boy with WS1, one of four clinicat types of WS. He exhibited white forelock, hypopigmented macules and patches, heterochromia irides, and dystopia canthorum.

  5. Cardiorenal syndrome type 4: a review.

    PubMed

    Clementi, Anna; Virzì, Grazia Maria; Goh, Ching Yan; Cruz, Dinna N; Granata, Antonio; Vescovo, Girogio; Ronco, Claudio

    2013-04-01

    There is a bidirectional and complex relationship between the heart and kidneys. This interaction is physical, chemical as well as biological and is also reflected in a strong connection between renal and cardiovascular diseases. Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to an impairment of cardiac function, with ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. The incidence of CKD is increasing, and CRS type 4 is becoming a major public health problem associated with a high morbidity and mortality. In this study, we briefly review the epidemiology and pathophysiology of CRS type 4, the role of biomarkers in its early identification, and its management.

  6. Type 3 Pfeiffer syndrome with normal thumbs.

    PubMed

    Kerr, N C; Wilroy, R S; Kaufman, R A

    1996-12-11

    We report on a male infant with extremely shallow orbits, spontaneous luxation of the eyes out of the eyelids, hypoplastic midface, broad, medially rotated great toes, and respiratory distress due to severe bilateral posterior choanal stenosis. At 4 days he had open cranial sutures (both by palpation and radiological examination). Subsequent radiologic studies demonstrated: thickening of the skull base, vertebral anomalies, flattening of the olecranon fossae with dislocated radii, and triangular shape of the proximal phalanx of the first toes. Our patient had manifestations of type 3 Pfeiffer syndrome (PS). However, the finding of normal thumbs has not been reported in type 3 PS. Point mutations in fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor receptor-2 (FGFR2) have been reported in familial and sporadic cases of PS, but were not found in this patient. Recognizing type 3 PS, despite variability in expression, is important for genetic counseling, prognosis, and decision-making regarding craniofacial surgery.

  7. Current Understanding of Usher Syndrome Type II

    PubMed Central

    Yang, Jun; Wang, Le; Song, Hongman; Sokolov, Maxim

    2012-01-01

    Usher syndrome is the most common deafness-blindness caused by genetic mutations. To date, three genes have been identified underlying the most prevalent form of Usher syndrome, the type II form (USH2). The proteins encoded by these genes are demonstrated to form a complex in vivo. This complex is localized mainly at the periciliary membrane complex in photoreceptors and the ankle-link of the stereocilia in hair cells. Many proteins have been found to interact with USH2 proteins in vitro, suggesting that they are potential additional components of this USH2 complex and that the genes encoding these proteins may be the candidate USH2 genes. However, further investigations are critical to establish their existence in the USH2 complex in vivo. Based on the predicted functional domains in USH2 proteins, their cellular localizations in photoreceptors and hair cells, the observed phenotypes in USH2 mutant mice, and the known knowledge about diseases similar to USH2, putative biological functions of the USH2 complex have been proposed. Finally, therapeutic approaches for this group of diseases are now being actively explored. PMID:22201796

  8. Neurofibromatosis type 1 with overlap Turner syndrome and Klinefelter syndrome.

    PubMed

    Hatipoglu, Nihal; Kurtoglu, Selim; Kendirci, Mustafa; Keskin, Mehmet; Per, Hüseyin

    2010-02-01

    Turner's syndrome is a sex chromosome disorder. Klinefelter's syndrome is one of the most severe genetic diseases. Neurofibromatosis is an autosomal dominant disorder characterized by cafe-au-lait spots and fibromatous tumors of the skin. In this article, we report the overlap of neurofibromatosis-1 with Turner and Klinefelter syndromes. Thus, these disorders might overlap within the same patient. Due to these cases, we suggest that each patient with Turner-like symptoms or Klinefelter's-like syndrome, be carefully examined for café au lait macules before the initiation of hormone replacement treatment.

  9. Autoimmune Polyglandular Syndrome Type 3 with Anorexia

    PubMed Central

    Kahara, Toshio; Wakakuri, Hitomi; Takatsuji, Juri; Motoo, Iori; Shima, Kosuke R.; Ishikura, Kazuhide; Usuda, Rika; Noda, Yatsugi

    2012-01-01

    A 71-year-old man with diabetes mellitus visited our hospital with complaints of anorexia and weight loss (12 kg/3 months). He had megaloblastic anemia, cobalamin level was low, and autoantibody to intrinsic factor was positive. He was treated with intramuscular cyanocobalamin, and he was able to consume meals. GAD autoantibody and ICA were positive, and he was diagnosed with slowly progressive type 1 diabetes mellitus (SPIDDM). Thyroid autoantibodies were positive. According to these findings, he was diagnosed with autoimmune polyglandular syndrome type 3 with SPIDDM, pernicious anemia, and Hashimoto's thyroiditis. Extended periods of cobalamin deficiency can cause serious complications such as ataxia and dementia, and these complications may not be reversible if replacement therapy with cobalamin is delayed. Although type 1 diabetes mellitus with coexisting pernicious anemia is very rare in Japan, physicians should consider the possibility of pernicious anemia when patients with diabetes mellitus have cryptogenic anorexia with the finding of significant macrocytosis (MCV > 100 fL). PMID:23304573

  10. What Are the Types and Phases of Rett Syndrome?

    MedlinePlus

    ... are the types? What are common symptoms? How many people are affected/at risk? ... are the types & phases of Rett syndrome? Skip sharing on social media links Share this: Page Content There are two ...

  11. Waardenburg syndrome type 2: an orthodontic perspective.

    PubMed

    Şuhani, Raluca Diana; Şuhani, Mihai Flaviu; Muntean, Alexandrina; Mesaroş, Michaela Florica; Badea, Mîndra Eugenia

    2015-01-01

    Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.

  12. A patient with ascending aortic dilatation, similar to phenotypes of connective tissue disorders.

    PubMed

    Onrat, S T; Emmiler, M; Sivaci, Y; Söylemez, Z; Ozgöz, A; Imirzalioğlu, N

    2009-04-14

    We report on the clinical and molecular findings of a patient who presented alopecia, epicanthus, micrognathia, retrognathia, high arched palate, hypertelorism, Chiari type I malformation, mixed-type hearing loss but with normal heartbeat Q-T interval, malformed earlobes, down-slanted palpebral fissures, downturned corners of the mouth, syndactyly, atopic eczema, and seizures. The patient was a male adult, 23 years old, with short stature (153 cm) and low weight (50.5 kg), due to severe aortic insufficiency and dilatation of the ascending aorta. Conventional cytogenetic screening did not show any chromosomal gains or losses. Molecular genetic screening was conducted for gene mutations involved in various syndromes; the mutations found included [beta-fibrinogen -455 G>A wt/wt (wt/mut), PAI-1 4G/5G (4G/4G), HPA1 a/b (a/a), MTHFR C677T wt/wt (wt/mut), ACE I/D (I/I), and Apo E E3/E4]. Many clinical and molecular genetics findings overlapped with other conditions associated with arterial tortuosity and arterial aneurysms, including the Marfan, Ehler-Danlos, Shprintzen-Goldberg, and Loeys-Dietz syndromes. Although a diagnosis of Shprintzen-Goldberg syndrome was based on clinical findings and radiographic findings indicate other syndromes, aortic root dilatation seems to be a new symptom, similar to phenotypes of connective tissue disorders. The unique grouping of clinical manifestations in this patient and the molecular genetics findings lead us to suggest that this case could be an example of a previously unrecognized syndrome.

  13. Meretoja's Syndrome: Lattice Corneal Dystrophy, Gelsolin Type

    PubMed Central

    Abreu, C.; Neves, M.; Oliveira, L.; Beirão, M.

    2017-01-01

    Lattice corneal dystrophy gelsolin type was first described in 1969 by Jouko Meretoja, a Finnish ophthalmologist. It is caused by an autosomal dominant mutation in gelsolin gene resulting in unstable protein fragments and amyloid deposition in various organs. The age of onset is usually after the third decade of life and typical diagnostic triad includes progressive bilateral facial paralysis, loose skin, and lattice corneal dystrophy. We report a case of a 53-year-old female patient referred to our Department of Ophthalmology by severe dry eye and incomplete eyelid closure. She had severe bilateral facial paresis, significant orbicularis, and perioral sagging as well as hypoesthesia of extremities and was diagnosed with Meretoja's syndrome at the age of 50, confirmed by the presence of gelsolin mutation. At our observation she had bilateral diminished tear film break-up time and Schirmer test, diffuse keratitis, corneal opacification, and neovascularization in the left eye. She was treated with preservative-free lubricants and topical cyclosporine, associated with nocturnal complete occlusion of both eyes, and underwent placement of lacrimal punctal plugs. Ocular symptoms are the first to appear and our role as ophthalmologists is essential for the diagnosis, treatment, and monitoring of ocular alterations in these patients. PMID:28250773

  14. Cholesterol and Alzheimer Type Dementia among Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Buckley, Frank

    2008-01-01

    This article reports a summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome. Warren Zigman and colleagues followed 123 adults with Down syndrome between May 1998 and April 2006. The participants were aged between 41 and 78 years at the…

  15. Oro-facial-digital syndrome type II with otolaryngological manifestations.

    PubMed

    Havle, A; Shedge, S; Malashetti, S; Jain, V

    2015-01-01

    We present a case of oro-facial-digital syndrome type II (Mohr's syndrome) which is characterized by malformations of the oral cavity, face and digits. The facial and oral features include tongue nodules, cleft or high-arched palate, missing teeth, broad nose; cleft lip. The digital features include clinodactyly, polydactyly, syndactyly, brachydactyly and duplication of the hallux.

  16. Intestinal malrotation in a patient with Pfeiffer syndrome type 2.

    PubMed

    Zarate, Yuri A; Putnam, Philip E; Saal, Howard M

    2010-11-01

    Pfeiffer syndrome is a pleiotropic disorder characterized by multiple suture craniosynostosis, broad and medially deviated thumbs and great toes, and variable cutaneous syndactyly. We present the case of a 16-month-old boy with Pfeiffer syndrome type 2 who presented with intestinal malrotation for which the diagnosis was delayed. This is a rare complication of Pfeiffer syndrome, with few reported cases in the literature. This case illustrates the importance of recognizing gastrointestinal malrotation as a possible cause of feeding intolerance and persistent vomiting in patients with the severe forms of Pfeiffer syndrome.

  17. Gait Strategy in Patients with Ehlers-Danlos Syndrome Hypermobility Type and Down Syndrome

    ERIC Educational Resources Information Center

    Rigoldi, Chiara; Galli, Manuela; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Tenore, Nunzio; Albertini, Giorgio

    2012-01-01

    People suffering from Ehlers-Danlos syndrome (EDS) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission. The same condition is present in people suffering from Down syndrome (DS) even if their clumsy movements are due to cerebral and cognitive impairments. The aim of this study was to…

  18. Type I interferons in Sjögren's syndrome.

    PubMed

    Yao, Yihong; Liu, Zheng; Jallal, Bahija; Shen, Nan; Rönnblom, Lars

    2013-03-01

    Sjögren's syndrome is a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary and lachrymal glands resulting in dry eyes and mouth. Genetic predisposition, pathogenic infections and hormones have been implicated in the pathogenesis of the disease. Studies in the last several years have revealed marked over-expression of the type I interferon (IFN)-inducible genes in the peripheral blood and salivary glands of patients with Sjögren's syndrome. The expression of the type I IFN-inducible genes in Sjögren's syndrome also positively correlates to titers of anti-Ro and anti-La autoantibodies, which are typical for this disease. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN production and activated pDC are detected in minor salivary gland biopsies from patients with primary Sjögren's syndrome. In addition, polymorphisms in genes important both for the production and response to type I IFN are associated to increased risk for Sjögren's syndrome. Because type I IFN bears a variety of biological functions, such as defense against viral infections and activation of the immune system, these results suggest that the type I IFN system has an important role in the pathogenesis of Sjögren's syndrome. A variety of mechanisms causing an activation of the type I IFN system are discussed in this review. Given the pivotal role of type I IFN in the disease process, therapeutic interventions targeting the type I IFN signaling pathway have the potential to benefit the patients with elevated type I IFN status and such hypothesis needs to be carefully evaluated in clinical development.

  19. Outlet type of interventricular septal defect in SanFilippo type-B syndrome.

    PubMed

    Kourouklis, S; Chatzis, D; Skafida, M; Liagkas, K; Paradellis, G; Kyriakides, Z

    2007-11-15

    Mucopolysaccharidoses (MPS) are a heterogeneous group of lysosomal storage disorders, due to deficiency of glycosaminoglycans breakdown enzymes. MPS type III is also known as SanFilippo syndrome, which is further subdivided into four distinct forms--A, B, C and D--caused by different enzyme deficiencies, but with similar clinical characteristics. Cardiac involvement in SanFilippo syndrome is less common compared with the other MPS types. In our case report, outlet type of interventricular septal defect was echocardiographically diagnosed in a fifteen year-old boy with known history of SanFilippo type-B syndrome, which, to our knowledge, has not yet been reported.

  20. Natal molars in Pfeiffer syndrome type 3: a case report.

    PubMed

    Alvarez, M P; Crespi, P V; Shanske, A L

    1993-01-01

    The following report is the first documented case of natal teeth associated with a recently described new entity, Pfeiffer syndrome type 3. The clinical manifestations consistent with the spectrum of this rare disorder are described with an emphasis on the concomitant natal teeth. Pfeiffer syndrome type 3 is one of the craniosynostosis syndromes and has been described in only two patients to date. Both mandibular incisors and maxillary molar natal teeth were found. Natal teeth are teeth, which are present in the oral cavity at birth. They are often associated with developmental abnormalities and recognized syndromes. Their incidence ranges from 1 in 2,000 to 3,500 births. The natal teeth found in this infant included both the mandibular primary incisors and maxillary primary first molars bilaterally. The clinical and histological considerations of natal teeth and their management are discussed. The presence of multiple natal teeth is extremely rare.

  1. Burning mouth syndrome due to herpes simplex virus type 1.

    PubMed

    Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don

    2015-04-01

    Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later.

  2. Type 2 leprosy reaction with Sweet's syndrome-like presentation*

    PubMed Central

    Chiaratti, Francielle Chiavelli; Daxbacher, Egon Luiz Rodrigues; Neumann, Antonielle Borges Faria; Jeunon, Thiago

    2016-01-01

    Leprosy is a chronic disease characterized by manifestations in the peripheral nerves and skin. The course of the disease may be interrupted by acute phenomena called reactions. This article reports a peculiar case of type 2 leprosy reaction with Sweet's syndrome-like features as the first clinical manifestation of leprosy, resulting in a delay in the diagnosis due to unusual clinical presentation. The patient had clinical and histopathological features reminiscent of Sweet's syndrome associated with clusters of vacuolated histiocytes containing acid-fast bacilli isolated or forming globi. Herein, it is discussed how to recognize type 2 leprosy reaction with Sweet's syndrome features, the differential diagnosis with type 1 leprosy reaction and the treatment options. When this kind of reaction is the first clinical presentation of leprosy, the correct diagnosis might be not suspected clinically, and established only with histopathologic evaluation. PMID:27438203

  3. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  4. [Acute coronary syndrome after hornet bite, type II Kounis syndrome - a case report].

    PubMed

    Alihodzić, Hajriz; Ilić, Boris; Mladina, Nada; Mrsić, Denis

    2013-01-01

    Kounis syndrome is an accidental occurrence of acute coronary syndrome associated with anaphylaxis, where acute inflammatory mediators cause the spasm of coronary arteries with the erosion and rupture of atheromatous plaque. We present a 53-year-old male who during the treatment of anaphylaxis after a hornet bite developed acute anteroseptal myocardial infarction. The diagnosis of type II Kounis syndrome was proven by electrocardiographic abnormalities and biochemical markers with clinical manifestation of acute coronary syndrome, and was associated with anaphylaxis which demanded prehospital treatment of the patient after the hornet bite. Anaphylaxis after a hornet bite requires consideration of acute coronary syndrome if patients have chest pain and hemodynamic impairment, as these conditions occur infrequently but demand additional diagnostics and adequate treatment.

  5. Trichorhinophalangeal syndrome type 1: A case report with literature review

    PubMed Central

    Candamourty, Ramesh; Venkatachalam, Suresh; Karthikeyan, B.; Babu, M. R. Ramesh

    2012-01-01

    Trichorhinophalangeal syndrome is a very rare genetic disorder, where damage and mutation to the number 8 chromosome affects sufferers in numerous ways. The syndrome has three types, all characterized by abnormally short stature, sparse hair, short deformed fingers with cone-shaped epiphyses visible in radiographs. Type I is the most common. Type II is characterized by the development of multiple bony exostoses and frequently, mental disability. Type III is a more severe form of type I and is associated with short stature. This report presents a 28-year-old man who had the characteristic features of type I with the presence of multiple erupted supernumerary teeth with normal mentation and karyotyping with high resolution G banding displayed normal chromosomal complements. PMID:23225991

  6. Clinical and morphological features of Waardenburg syndrome type II.

    PubMed

    Mullaney, P B; Parsons, M A; Weatherhead, R G; Karcioglu, Z A

    1998-01-01

    Evaluation of 4-month-old girl who presented with congenital cataracts revealed heterochromia iridis, fundus hypopigmentation, residual white forelock and sensory neural hearing loss--findings consistent with Waardenburg syndrome type II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in the brown. Electron microscopic examination showed a significant (p = 0.0001) reduction in melanosome size in the blue iris, and the nerve endings contained fewer vesicles. A defect in neural crest cell migration and melanin synthesis may be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

  7. Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III.

    PubMed

    Cheng, Jem L; Au, Jason S; Guzman, Juan C; Morillo, Carlos A; MacDonald, Maureen J

    2016-12-22

    The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.

  8. Nocturnal hyperglycaemia in type 2 diabetes with sleep apnoea syndrome.

    PubMed

    Fendri, Salha; Rose, Dominique; Myambu, Sonia; Jeanne, Sandrine; Lalau, Jean-Daniel

    2011-01-01

    We assessed glycaemic status in 26 overweight or obese people with type 2 diabetes suspected of having sleep apnoea syndrome (SAS). In people with SAS (n=13), nocturnal glycaemia was 38% higher, independent of body mass index (particularly during rapid eye movement sleep) compared with non-SAS subjects (p<0.008).

  9. Free flap transfer for complex regional pain syndrome type II

    PubMed Central

    Matsuda, Ken; Kikuchi, Mamoru; Murase, Tsuyoshi; Hosokawa, Ko; Shibata, Minoru

    2014-01-01

    Abstract A patient with complex regional pain syndrome type II was successfully treated using free anterolateral thigh flap transfer with digital nerve coaptation to the cutaneous nerve of the flap. Release of the scarred tissue and soft tissue coverage with targeted sensory nerve coaptation were useful in relieving severe pain. PMID:27252946

  10. [Familial partial lipodystrophy type 1. A rare or underdiagnosed syndrome?].

    PubMed

    Soutelo, Jimena; Grüneisen, Mariana; Fritz, Clara; Sordo, Laura; Powazniak, Yanina; Lutfi, Rubén

    2015-01-01

    Familial partial lipodystrophy (FPL) type 1 is a syndrome characterized by loss of subcutaneous fat in arms and legs and an excess of body fat in face, neck, and torso. This rare syndrome is usually diagnosed when patients present cardiovascular complications or pancreatitis due to the severe metabolic abnormalities. Here we present the case of a 45 year old diabetic female without any pathological family history, a poor glycemic control (HbA1c 11.7%), hypertriglideridemia (3000 mg/dl), a body mass index (BMI) of 38, thin limbs, subcutaneous fat loss in gluteal area and ledge of fat above them, prominent veins in lower extremities, moon face, and acanthosis nigricans; as well as hypertension (150/100 mmHg) and subcutaneous folds measuring less than average were observed. Hypercortisolism was discarded and leptin levels were measured (16.8 mg/ml, VR: BMI > 30: 50 mg/ml). Due to these clinical and biochemical manifestations, and low leptin levels (16.8 mg/ml), Kobberling syndrome was suspected; however, LMNA mutation analysis was negative. Changes in lifestyle and treatment with fenofibrate, biphasic insulin 50/50, and enalapril were initiated showing a a significant metabolic improvement: HbA1c (7.8%) and TG (243 mg/dl). FPL type 1 is a familial disease, although there are spontaneous cases. No specific mutation is responsible for this syndrome. Due to its clinical manifestations, Cushing syndrome must be discarded.

  11. Congenital Chylous Ascites and Ehlers-Danlos Syndrome Type VI

    PubMed Central

    Pohl, John; Esty, Brittany; Sempler, Jessica K.; Carey, John C.; O’Gorman, Molly A.

    2016-01-01

    We report the first observation of a patient with contgenital chylous ascites (CCA) and Ehlers-Danlos syndrome type VI due to primary lymphatic defect with additional vascular anomaly. CCA is a rare condition, and there is limited understanding of its pathophysiology and treatment options. We also review the patient’s treatment course mitigated with octreotide and total parenteral nutritional support, as there are no current established guidelines for CCA. Early recognition of possible association with Ehlers-Danlos syndrome is important for quick intervention and successful management of pediatric patients. PMID:28119937

  12. Mauriac syndrome: growth failure and type 1 diabetes mellitus.

    PubMed

    Kim, Mimi S; Quintos, J B

    2008-08-01

    Growth failure in Type 1 Diabetes Mellitus (T1DM) can occur for several reasons. Mauriac syndrome is a rare cause of severe growth failure in T1DM. There may be different forms and etiologies involved in Mauriac syndrome. However, there are common features noted in these patients. We have compiled a review of cases reported in English in the last 30 years. With adequate insulin treatment there is reversal of growth failure and hepatomegaly if present. However, overly aggressive insulin delivery could result in rapid deterioration of diabetic retinopathy and nephropathy. Close monitoring of growth and pubertal maturation in children with T1DM is essential.

  13. Adult presentation of Bartter syndrome type IV with erythrocytosis

    PubMed Central

    Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

    2015-01-01

    Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis. PMID:26537508

  14. Ehlers-Danlos syndrome, classical type.

    PubMed

    Bowen, Jessica M; Sobey, Glenda J; Burrows, Nigel P; Colombi, Marina; Lavallee, Mark E; Malfait, Fransiska; Francomano, Clair A

    2017-02-13

    Classical EDS is a heritable disorder of connective tissue. Patients are affected with joint hypermobility, skin hyperextensibilty, and skin fragility leading to atrophic scarring and significant bruising. These clinical features suggest consideration of the diagnosis which then needs to be confirmed, preferably by genetic testing. The most recent criteria for the diagnosis of EDS were devised in Villefranche in 1997. [Beighton et al. (1998); Am J Med Genet 77:31-37]. The aims set out in the Villefranche Criteria were: to enable diagnostic uniformity for clinical and research purposes, to understand the natural history of each subtype of EDS, to inform management and genetic counselling, and to identify potential areas of research. The authors recognized that the criteria would need updating, but viewed the Villefranche nosology as a good starting point. Since 1997, there have been major advances in the molecular understanding of classical EDS. Previous question marks over genetic heterogeneity have been largely surpassed by evidence that abnormalities in type V collagen are the cause. Advances in molecular testing have made it possible to identify the causative mutation in the majority of patients. This has aided the further clarification of this diagnosis. The aim of this literature review is to summarize the current knowledge and highlight areas for future research. © 2017 Wiley Periodicals, Inc.

  15. Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

    PubMed Central

    Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

    2015-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  16. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria.

    PubMed

    Liu, X Z; Newton, V E; Read, A P

    1995-01-02

    The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. Mapping WS Type II requires accurate diagnosis within affected families. To establish diagnostic criteria for WS Type II, 81 individuals from 21 families with Type II WS were personally studied, and compared with 60 personally studied patients from 8 families with Type I and 253 cases of WS (Type I or II) from the literature. Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. Both were more common in Type II than in Type I. Other clinical manifestations, such as white forelock and skin patches, were more frequent in Type I. We estimate the frequency of phenotypic traits and propose diagnostic criteria for WS Type II. In practice, a diagnosis of WS Type II can be made with confidence given a family history of congenital hearing loss and pigmentary disorders, where individuals have been accurately measured for ocular distances to exclude dystopia canthorum.

  17. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history.

    PubMed

    Tinkle, Brad; Castori, Marco; Berglund, Britta; Cohen, Helen; Grahame, Rodney; Kazkaz, Hanadi; Levy, Howard

    2017-03-01

    The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc.

  18. DRESS syndrome associated with type 2 diabetes in a child

    PubMed Central

    Erdem, Semiha Bahceci; Bag, Ozlem; Karkiner, Canan Sule Unsal; Korkmaz, Huseyin Anil; Can, Demet

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to “drug rash with eosinophilia and systemic symptoms syndrome” such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID:26862317

  19. [Syndrome of blue sclerae and keratoglobus (ocular type of Ehlers-Danlos syndrome (author's transl)].

    PubMed

    Behrens-Baumann, W; Gebauer, H J; Langenbeck, U

    1977-12-31

    Two children born on Crete of consanguinous parents presented the following manifestations of the ocular type of Ehlers-Danlos syndrome (EDS): blue sclerae, keratoglobus and rupture of cornea following minor trauma. In cultivated fibroblasts of one of the patients there was no evidence of defective lysine hydroxylation. The possible relation of our case to a recent similar report by Judisch et al. (1976) is discussed. The ocular type of EDS may be genetically heterogenous. Provisionally, we propose for cases with normal lysyl hydroxylation in vitro the term 'type VIII of EDS'.

  20. [Oral-facial-digital syndrome type I. A case report].

    PubMed

    Leonardi, R; Gallone, M; Sorge, G; Greco, F

    2004-04-01

    Oral-facial-digital syndrome type I (OFDI) is a congenital X-linked dominant disorder characterized by anomalies of the oral cavity, face and digits sometimes associated to cerebral malformations and polycystic kidney disease. The gene, responsible for this syndrome, is ofd1. Clinically it is seen only in females. Lesions of the mouth include median pseudoclefting of the upper lip, clefts of the palate and tongue, and dental anomalies (missing or supernumerary teeth, enamel hypoplasia, and teeth malpositions). Dysmorphic features affecting the head include hypertelorism, frontal bossing, micrognathia, facial asymmetry and broadened nasal ridge. The digital abnormalities are syndactyly, clinodactyly, brachydactyly and, rarely, pre or post-axial polydactyly. Less frequently ex-pressed phenotypic anomalies include skin milia, alopecia, deafness and trembling. Sometimes the diagnosis of OFDI can be difficult because there is an overlap with other types of oral-facial-digital syndromes. A sporadic case of OFDI, with 7 lower incisors, both in the primary and permanent dentition, is reported. This dental anomaly is very unusual because in literature only supernumerary cuspids are reported. In the light of this case, the authors discuss the oral phenotypic expression of ofd1 gene and its role in human odontogenesis.

  1. Current Evidence and Insights about Genetics in Thoracic Aorta Disease

    PubMed Central

    Muneretto, Claudio

    2013-01-01

    Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve. PMID:24453931

  2. Current evidence and insights about genetics in thoracic aorta disease.

    PubMed

    Bisleri, Gianluigi; Bagozzi, Lorenzo; Muneretto, Claudio

    2013-01-01

    Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve.

  3. Advances in the pathogenesis of cardiorenal syndrome type 3.

    PubMed

    Clementi, Anna; Virzì, Grazia Maria; Brocca, Alessandra; de Cal, Massimo; Pastori, Silvia; Clementi, Maurizio; Granata, Antonio; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) leads to the development of acute cardiac injury or dysfunction. In general, there is limited understanding of the pathophysiologic mechanisms involved in CRS type 3. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Experimental data suggest that cardiac dysfunction may be related to immune system activation, inflammatory mediators release, oxidative stress, and cellular apoptosis which are well documented in the setting of AKI. Moreover, significant derangements, such as fluid and electrolyte imbalance, metabolic acidosis, and uremia, which are typical features of acute kidney injury, may impair cardiac function. In this review, we will focus on multiple factors possibly involved in the pathogenesis issues regarding CRS type 3.

  4. Clinical presentations of Ehlers Danlos syndrome type IV.

    PubMed Central

    Pope, F M; Narcisi, P; Nicholls, A C; Liberman, M; Oorthuys, J W

    1988-01-01

    Ehlers Danlos syndrome type IV is an often lethal disease caused by various mutations of type III collagen genes. It presents in infancy and childhood in several ways, and the symptoms and signs include low birth weight, prematurity, congenital dislocation of the hips, easy inappropriate bruising (sometimes suspected as child battering), and a diagnostic facial phenotype. These features predict a lethal adult disease often complicated by fatal arterial rupture in early or middle adult life. Most affected patients can be diagnosed from radiolabelled collagen protein profiles by polyacrylamide gel electrophoresis. Prenatal diagnosis by specific type III collagen restriction fragment length polymorphisms is possible in some families, and will become increasingly important. Prenatal diagnosis and prevention of the disease in selected families is already possible and will be widely available in the future. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 PMID:3178263

  5. Clinical findings in obligate carriers of type I Usher syndrome

    SciTech Connect

    Wagenaar, M.; Rahe, B. ter; Aarem, A. van; Huygen, P.; Admiraal, R.

    1995-11-20

    Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. 29 refs., 1 fig., 3 tabs.

  6. Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy.

    PubMed

    Rajyalakshmi, R; Chakrapani, R N B

    2016-01-01

    Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1), RAB27A (GS2), and MLPH (GS3) genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.

  7. Corneal abnormalities in Ehlers-Danlos syndrome type VI.

    PubMed

    Cameron, J A

    1993-01-01

    Eleven patients with blue sclera, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents were examined between January 1983 and September 1991. The clinical diagnosis was consistent with the Ehlers-Danlos syndrome type VI phenotype in all patients. A "halo" sign at the limbus was present in all patients. Corneal rupture occurred in seven patients (nine eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in three patients. Bilateral microcornea was present in one patient and two patients had a unilateral increased corneal diameter as a result of secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in five patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus.

  8. Anisometropic amblyopia in a case of type 2 Waardenburg syndrome.

    PubMed

    Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk

    2013-12-18

    This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail.

  9. Autoimmune Polyglandular Syndrome Type 2: A Rare Condition in Childhood

    PubMed Central

    Kırmızıbekmez, Heves; Yeşiltepe Mutlu, Rahime Gül; Demirkıran Urgancı, Nafiye; Öner, Ayşe

    2015-01-01

    Autoimmune polyglandular syndrome type 2 is defined as the occurrence of Addison’s disease concomitantly with autoimmune thyroid disease and/or type 1 diabetes mellitus. An 11-year-old boy with Hashimoto’s disease, Addison’s disease, celiac disease and Langerhans islet cell autoimmunity is described in this case report. Treatment of an endocrine disease may also trigger the onset of another endocrine disease. This case report underlines the importance of early recognition and treatment of critical endocrine diseases as well as the necessity to investigate pediatric patients with autoimmune diseases for coexisting conditions. Furthermore, the role of psychological stress as an inducer of autoimmunity was also discussed. PMID:25800482

  10. Anisometropic amblyopia in a case of type 2 Waardenburg syndrome

    PubMed Central

    Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk

    2013-01-01

    This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail. PMID:24351514

  11. Ehlers-Danlos Syndrome Type IV: A Case Report.

    PubMed

    Soo-Hoo, Sarah; Porten, Brandon R; Engstrom, Bjorn I; Skeik, Nedaa

    2016-04-01

    Ehlers-Danlos syndrome (EDS) encompasses a group of rare genetic connective tissue disorders. The vascular type (type IV) poses the most serious risk to patients. Diagnosis is usually difficult, especially if patients lack a family history. Life-threatening vascular emergency such as dissection or rupture can be the first presenting symptom. Management of the disease can pose a clinical challenge due to the emergency of presentation, tissue friability, and lack of clear management recommendations. We report a unique case of a 40-year-old man who presented with a ruptured celiac artery and a strong family history of EDS. This case highlights the difficulties and complications associated with treating this uncommon and serious disease.

  12. Mutations in PIEZO2 Cause Gordon Syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5

    PubMed Central

    McMillin, Margaret J.; Beck, Anita E.; Chong, Jessica X.; Shively, Kathryn M.; Buckingham, Kati J.; Gildersleeve, Heidi I.S.; Aracena, Mariana I.; Aylsworth, Arthur S.; Bitoun, Pierre; Carey, John C.; Clericuzio, Carol L.; Crow, Yanick J.; Curry, Cynthia J.; Devriendt, Koenraad; Everman, David B.; Fryer, Alan; Gibson, Kate; Giovannucci Uzielli, Maria Luisa; Graham, John M.; Hall, Judith G.; Hecht, Jacqueline T.; Heidenreich, Randall A.; Hurst, Jane A.; Irani, Sarosh; Krapels, Ingrid P.C.; Leroy, Jules G.; Mowat, David; Plant, Gordon T.; Robertson, Stephen P.; Schorry, Elizabeth K.; Scott, Richard H.; Seaver, Laurie H.; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Sehime G.; Weaver, David D.; Whiteford, Margo; Williams, Marc S.; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.

    2014-01-01

    Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher’s exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition. PMID:24726473

  13. Chronic pain in hypermobility syndrome and Ehlers–Danlos syndrome (hypermobility type): it is a challenge

    PubMed Central

    Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul HH

    2015-01-01

    Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers–Danlos syndrome. However, within the Ehlers–Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers–Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3). PMID:26316810

  14. Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility type): it is a challenge.

    PubMed

    Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul Hh

    2015-01-01

    Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers-Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3).

  15. [Clinical practice guideline 'Complex regional pain syndrome type I'].

    PubMed

    Perez, R S G M; Zollinger, P E; Dijkstra, P U; Thomassen-Hilgersom, I L; Zuurmond, W W A; Rosenbrand, C J G M; Geertzen, J H B

    2007-07-28

    The development and treatment ofthe complex regional pain syndrome type I (CRPS-I) are a subject of much discussion. Using the method for the development ofevidence-based guidelines, a multidisciplinary guideline for the diagnosis and treatment of this syndrome has been drawn up. The diagnosis of CRPS-I is based on the clinical observation of signs and symptoms. For pain treatment, the WHO analgesic ladder is advised up to step z. In case of pain ofa neuropathic nature, anticonvulsants and tricyclic antidepressants may be considered. For the treatment ofinflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. In order to enhance peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used for a cold extremity ifvasodilatory medication produces insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, the use of vitamin C is recommended. Adequate perioperative analgesia, limitation of operation time and limited use of bloodlessness are advised for the secondary prevention of CRPS-I. Use of regional anaesthetic techniques can also be considered in this connection.

  16. Ehlers-Danlos Syndrome Type VIIC: A Mexican Case Report

    PubMed Central

    Rincón-Sánchez, Ana Rosa; Arce, Irma Elia; Tostado-Rabago, Enrique Alejandro; Vargas, Alberto; Padilla-Gómez, Luis Alfredo; Bolaños, Alejandro; Barrios-Guyot, Selenne; Anguiano-Alvarez, Víctor Manuel; Ledezma-Rodríguez, Víctor Chistian; Islas-Carbajal, María Cristina; Rivas-Estilla, Ana María; Feria-Velasco, Alfredo; Dávalos, Nory Omayra

    2012-01-01

    Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders whose primary clinical features include soft and extensible skin, articular hypermobility and tissue fragility. EDS type VIIC or ‘human dermatosparaxis’ is an autosomal recessive disease characterized by severe skin fragility and sagging redundant skin (major criteria) with a soft, doughy texture, easy bruising, premature rupture of fetal membranes and large hernias (minor criteria). Dermatosparaxis (meaning ‘tearing of skin’), which has been described in several non-human species, is a disorder of the connective tissue resulting from a deficiency of the enzyme that cleaves the registration peptide off the N-terminal end of collagen after it has been secreted from fibroblasts. We describe a Mexican case from consanguineous parents with all the phenotypical characteristics previously described, plus skeletal abnormalities. PMID:22787447

  17. Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Morlino, Silvia; Pascolini, Giulia; Blundo, Carlo; Grammatico, Paola

    2015-03-01

    Gastrointestinal involvement is a well known complication of Ehlers-Danlos syndromes (EDSs), mainly in form of abdominal emergencies due to intestinal/abdominal vessels rupture in vascular EDS. In the last decade, a growing number of works investigated the relationship between a wide spectrum of chronic gastrointestinal complaints and various EDS forms, among which the hypermobility type (a.k.a. joint hypermobility syndrome; JHS/EDS-HT) was the most studied. The emerging findings depict a major role for gastrointestinal involvement in the health status and, consequently, management of JHS/EDS-HT patients. Nevertheless, fragmentation of knowledge limits its impact on practice within the boundaries of highly specialized clinics. In this paper, literature review on gastrointestinal manifestations in JHS/EDS-HT was carried out and identified papers categorized as (i) case-control/cohort studies associating (apparently non-syndromic) joint hypermobility and gastrointestinal involvement, (ii) case-control/cohort studies associating JHS/EDS-HT and gastrointestinal involvement, (iii) case reports/series on various gastrointestinal complications in (presumed) JHS/EDS-HT, and (iv) studies reporting gastrointestinal features in heterogeneous EDS patients' cohorts. Gastrointestinal manifestations of JHS/EDS-HT were organized and discussed in two categories, including structural anomalies (i.e., abdominal/diaphragmatic hernias, internal organ/pelvic prolapses, intestinal intussusceptions) and functional features (i.e., dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea), with emphasis on practice and future implications. In the second part of this paper, a summary of possible nutritional interventions in JHS/EDS-HT was presented. Supplementation strategies were borrowed from data available for general population with minor modifications in the light of recent discoveries in the pathogenesis of selected JHS/EDS-HT features.

  18. Endovascular repair of multiple infrageniculate aneurysms in a patient with vascular type Ehlers-Danlos syndrome.

    PubMed

    Domenick, Natalie; Cho, Jae S; Abu Hamad, Ghassan; Makaroun, Michel S; Chaer, Rabih A

    2011-09-01

    Patients with vascular type Ehler-Danlos syndrome can develop aneurysms in unusual locations. We describe the case of a 33-year-old woman with vascular type Ehlers-Danlos syndrome who developed metachronous tibial artery aneurysms that were sequentially treated with endovascular means.

  19. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    SciTech Connect

    Veith, G.D.; Broderius, S.J. )

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  20. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

    PubMed

    Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

    2015-03-01

    In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research.

  1. Interrupted aortic arch type B in A patient with cat eye syndrome.

    PubMed

    Belangero, Sintia Iole Nogueira; Bellucco, Fernanda Teixeira da Silva; Cernach, Mirlene C S P; Hacker, April M; Emanuel, Beverly S; Melaragno, Maria Isabel

    2009-05-01

    We report a patient with cat eye syndrome and interrupted aortic arch type B, a typical finding in the 22q11.2 deletion syndrome. Chromosomal analysis and fluorescent in situ hybridization (FISH) showed a supernumerary bisatellited isodicentric marker chromosome derived from chromosome 22. The segment from 22pter to 22q11.2 in the supernumerary chromosome found in our patient does not overlap with the region deleted in patients with the 22q11.2 deletion syndrome. However, the finding of an interrupted aortic arch type B is unusual in CES, although it is a frequent heart defect in the 22q11 deletion syndrome.

  2. Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB).

    PubMed

    Beesley, C E; Jackson, M; Young, E P; Vellodi, A; Winchester, B G

    2005-01-01

    Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive disease that is caused by the deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). NAGLU is involved in the degradation of the glycosaminoglycan (GAG) heparan sulphate, and a deficiency results in the accumulation of partially degraded GAGs inside lysosomes. Early clinical symptoms include hyperactivity, aggressiveness and delayed development, followed by progressive mental deterioration, although there are a small number of late-onset attenuated cases. The gene for NAGLU has been fully characterized and we report the molecular analysis of 18 Sanfilippo B families. In total, 34 of the 36 mutant alleles were characterized in this study and 20 different mutations were identified including 8 novel changes (R38W, V77G, 407-410del4, 703delT, A246P, Y335C, 1487delT, E639X). The four novel missense mutations were transiently expressed in Chinese hamster ovary cells and all were shown to decrease the NAGLU activity markedly, although A246P did produce 12.7% residual enzyme activity.

  3. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome)

    PubMed Central

    2011-01-01

    Background Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder caused by a deficiency of one of the enzymes involved in the degradation of heparan sulfate. MPS III is characterized by progressive mental deterioration resulting in severe dementia. A number of potentially disease-modifying therapies are studied. As preservation of cognitive function is the ultimate goal of treatment, assessment of cognitive development will be essential in order to evaluate treatment efficacy. However, no large scale studies on cognitive levels in MPS III patients, using formal psychometric tests, have been reported. Methods We aimed to assess cognitive development in all 73 living patients with MPS III in the Netherlands. Results Cognitive development could be assessed in 69 patients. In 39 of them developmental level was estimated > 3 months and formal psychometric testing was attempted. A remarkable variation in the intellectual disability was detected. Conclusions Despite special challenges encountered, testing failed in only three patients. The observed broad variation in intellectual disability, should be taken into account when designing therapeutic trials. PMID:21689409

  4. Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between Timothy syndrome types 1 and 2?

    PubMed

    Diep, Vinson; Seaver, Laurie H

    2015-11-01

    Timothy syndrome (TS) is a rare genetic condition that associates long QT syndrome, structural heart defects, dysmorphic facial features, syndactyly, seizures, developmental delay, and autism. Timothy syndrome type 1 is caused by a recurrent de novo mutation (p.Gly406Arg) in exon 8A of the L-type calcium channel gene CACNA1C. Timothy syndrome type 2 was originally reported to be associated with a more severe cardiac phenotype but without syndactyly. Timothy syndrome type 2 is caused by mutation in an alternatively spliced exon 8 of the CACNA1C gene. Other mutations in CACNA1C are also reported with long QT syndrome with and without syndromic features overlapping that described in Timothy syndrome. The purpose of this report is to describe the presentation, physical features and natural history of a 4-year-old girl with Timothy syndrome type 2 due to the recurrent p.Gly406Arg mutation in exon 8 of CACNA1C. She has similar facial features to Timothy syndrome type 1 without syndactyly. She is developmentally delayed without autism. She recently had her first episode of torsade de pointes associated with febrile illness and hypoglycemia. The findings in this case provide further information about the phenotype and natural history of CACNA1C exon 8 mutation and together with previously reported cases of Timothy syndrome question whether the clinical and molecular distinction between Timothy syndromes types 1 and 2 remains clinically useful.

  5. Understanding vascular-type Ehlers-Danlos syndrome and avoiding vascular complications

    PubMed Central

    Fenves, Andrew Z.

    2017-01-01

    Vascular-type Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disorder caused by a mutation in type III procollagen. It has the highest mortality rate among the six types of EDS. Patients with this syndrome often have typical medical histories and a characteristic physical examination. We present two patients with this rare disorder and highlight the diagnostic and treatment challenges. PMID:28127132

  6. [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

    PubMed

    Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

    2015-01-01

    Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory.

  7. Trichorhinophalangeal syndrome type II presenting with short stature in a child.

    PubMed

    Hazan, Filiz; Korkmaz, Hüseyin A; Yararbaş, Kanay; Wuyts, Wim; Tükün, Ajlan

    2016-12-01

    Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome) is a rare autosomal dominant contiguous gene syndrome, resulting from a microdeletion encompassing the EXT1 and the TRPS1 gene at 8q24 (MIM#150230). This syndrome combines the clinical features of two autosomal dominant disorders, trichorhinophalangeal syndrome type I (MIM#190350) and hereditary multiple osteochondromas type I (MIM # 133700). TRPSII is characterized by sparse scalp hair, a long nose with a bulbous tip, long flat philtrum, cone-shaped epiphyses of the phalanges, retarded bone age in infancy and multiple cartilaginous osteochondromas. We report a Turkish patient who had the clinical features and skeletal signs of TRPSII in whom a 13.8Mb deletion in 8q23.1- 8q24.13 was detected.

  8. Type 1 Kounis Syndrome in Patient with Idiopathic Anaphylaxis

    PubMed Central

    Makuc, Jana; Sekavčnik, Gregor

    2017-01-01

    Kounis syndrome represents the concurrence of acute coronary syndromes or anginal pain with allergic, hypersensitivity, and anaphylactic reactions. It can be associated with normal coronary angiogram or preexistent coronary pathology. Idiopathic anaphylaxis is defined as anaphylaxis without any identifiable precipitating agent or event. We present a case of male who experienced attacks of dyspnoea, hypoxemia, hypotension, purple-red skin, and chest pain over several years. He was diagnosed with idiopathic anaphylaxis. Based on the pattern of chest pain of ischemic origin during the attacks he was retrospectively diagnosed with Kounis syndrome. PMID:28255467

  9. [Ehler-Danlos syndrome (type V) with urethra bifida and polydactyly: an unusual combination].

    PubMed

    Manna, R; Modugno, I; Pala, M A; Caputo, S; Caradonna, E; Greco, A V

    1981-06-30

    Ehlers-Danlos syndrome is currently regarded as a connective tissue dysplasia. Its genetic, biochemical, histological and clinical features are described, together with a personal case in a patient who presented the fundamental symptoms, plus polydactyly and bifid urethra. This association had not been hitherto reported in the literature. The case itself is classed as Ehlers-Danlos syndrome type V.

  10. Chiari type 1 malformation in an infant with type 2 Pfeiffer syndrome: further evidence of acquired pathogenesis.

    PubMed

    Ranger, Adrianna; Al-Hayek, Ali; Matic, Damir

    2010-03-01

    There seems to be an association between type 1 Chiari malformation (CM) and some congenital craniosynostosis syndromes. Type 2 Pfeiffer syndrome is a condition associated with premature fusion of multiple cranial sutures, cloverleaf skull (kleeblatschädel deformity), prominent ptosis, thumb and first toe abnormalities, variable syndactyly, and mutated genes for type 1 or 2 fibroblast growth factor receptor. These children generally do poorly because of significant often severe neurologic and cognitive defects, and many die very young. Roughly half of all patients with Pfeiffer syndrome, and virtually all with type 2 disease, also have type 1 CM. Chiari malformation may not be congenital but acquired as a consequence of the skull deformities and other associated intracranial factors in patients with craniosynostosis. We report a term male infant with type 2 Pfeiffer syndrome, who was not noted to have any CM on initial brain imaging done at 2 months but in whom repeated imaging demonstrated clear evidence of CM by 4 months, despite reconstructive craniotomies and unilateral ventriculoperitoneal shunt insertion. Posterior fossa decompression yielded a good result. This patient provides further evidence to support the concept of acquired tonsillar herniation in patients with craniosynostosis syndromes. The etiology seems multifactorial and related to (1) the disproportionately slow growth of the skull relative to the brain, particularly in the posterior fossa, secondary to early fusion of skull sutures, in turn secondary to congenital deficiencies in fibroblast growth factor receptors; (2) impaired venous sinus drainage; (3) hydrocephalus; and (4) resultant elevations in intracranial pressure.

  11. Genetics Home Reference: type A insulin resistance syndrome

    MedlinePlus

    ... insulin resistance syndrome , insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes ... to the effects of insulin impairs blood sugar regulation and leads to diabetes mellitus. In females with ...

  12. Screening of three Usher syndrome type II candidate genes

    SciTech Connect

    Bloemker, B.K.; Swaroop, A.; Kimberling, W.J.

    1994-09-01

    Usher syndrome type II (US2) is an autosomal recessive disorder that results in blindness due to retinitis pigmentosa and congenital hearing loss. The disease affects approximately 1 in 20,000 individuals in the general population and is responsible for over 50% of all cases of deafness with blindness. The underlying US2 defect is unknown. The US2 gene has been localized to the 1q41 region of chromosome 1 by linkage studies. Three genes previously localized to 1q were analyzed to assess their candidacy as the US2 gene. These were evaluated by PCR assays using DNA from a YAC contig spanning the US2 region on chromosome 1. The first gene evaluated was the human choroideremia-like gene (hCHML), which had been mapped to chromosome 1q. The sequence on 1q is a homologue of the human choroideremia gene on chromosome X. Choroideremia is a degenerative disorder causing ocular pathology similar to that observed in US2 patients. Therefore, hCHML is a candidate for the US2 gene. Two cDNAs (A and B) from an enriched human retinal pigment epithelium library have been mapped to 1q41 by in situ hybridization. Both cDNAs are considered good candidates. The hCHML and cDNA A were ruled out as candidates for the US2 gene based on negative results from PCR assays performed on YACs spanning the US2 region. cDNA B could not be ruled out as a candidate for the US2 gene by these assays. Answers to many clinical questions regarding US2 will only be resolved after the gene is identified and characterized. Eventually, understanding the function and expression of the US2 gene will provide a basis for the development of therapy.

  13. Mechanisms of disease pathogenesis in long QT syndrome type 5

    PubMed Central

    Harmer, Stephen C.; Wilson, Andrew J.; Aldridge, Robert

    2010-01-01

    KCNE1 associates with the pore-forming α-subunit KCNQ1 to generate the slow (IKs) current in cardiac myocytes. Mutations in either KCNQ1 or KCNE1 can alter the biophysical properties of IKs and mutations in KCNE1 underlie cases of long QT syndrome type 5 (LQT5). We previously investigated a mutation in KCNE1, T58P/L59P, which causes severe attenuation of IKs. However, how T58P/L59P acts to disrupt IKs has not been determined. In this study, we investigate and compare the effects of T58P/L59P with three other LQT5 mutations (G52R, S74L, and R98W) on the biophysical properties of the current, trafficking of KCNQ1, and assembly of the IKs channel. G52R and T58P/L59P produce currents that lack the kinetic behavior of IKs. In contrast, S74L and R98W both produce IKs-like currents but with rightward shifted voltage dependence of activation. All of the LQT5 mutants express protein robustly, and T58P/L59P and R98W cause modest, but significant, defects in the trafficking of KCNQ1. Despite defects in trafficking, in the presence of KCNQ1, T58P/L59P and the other LQT5 mutants are present at the plasma membrane. Interestingly, in comparison to KCNE1 and the other LQT5 mutants, T58P/L59P associates only weakly with KCNQ1. In conclusion, we identify the disease mechanisms for each mutation and reveal that T58P/L59P causes disease through a novel mechanism that involves defective IKs complex assembly. PMID:19907016

  14. Mechanisms of disease pathogenesis in long QT syndrome type 5.

    PubMed

    Harmer, Stephen C; Wilson, Andrew J; Aldridge, Robert; Tinker, Andrew

    2010-02-01

    KCNE1 associates with the pore-forming alpha-subunit KCNQ1 to generate the slow (I(Ks)) current in cardiac myocytes. Mutations in either KCNQ1 or KCNE1 can alter the biophysical properties of I(Ks) and mutations in KCNE1 underlie cases of long QT syndrome type 5 (LQT5). We previously investigated a mutation in KCNE1, T58P/L59P, which causes severe attenuation of I(Ks). However, how T58P/L59P acts to disrupt I(Ks) has not been determined. In this study, we investigate and compare the effects of T58P/L59P with three other LQT5 mutations (G52R, S74L, and R98W) on the biophysical properties of the current, trafficking of KCNQ1, and assembly of the I(Ks) channel. G52R and T58P/L59P produce currents that lack the kinetic behavior of I(Ks). In contrast, S74L and R98W both produce I(Ks)-like currents but with rightward shifted voltage dependence of activation. All of the LQT5 mutants express protein robustly, and T58P/L59P and R98W cause modest, but significant, defects in the trafficking of KCNQ1. Despite defects in trafficking, in the presence of KCNQ1, T58P/L59P and the other LQT5 mutants are present at the plasma membrane. Interestingly, in comparison to KCNE1 and the other LQT5 mutants, T58P/L59P associates only weakly with KCNQ1. In conclusion, we identify the disease mechanisms for each mutation and reveal that T58P/L59P causes disease through a novel mechanism that involves defective I(Ks) complex assembly.

  15. Stickler Syndrome Type 1 with Short Stature and Atypical Ocular Manifestations

    PubMed Central

    Kapoor, Seema; Ikegawa, Shiro; Nishimura, Gen

    2016-01-01

    Stickler syndrome or hereditary progressive arthroophthalmopathy is a heterogeneous group of collagen tissue disorders, characterized by orofacial features, ophthalmological features (high myopia, vitreoretinal degeneration, retinal detachment, and presenile cataracts), hearing impairment, mild spondyloepiphyseal dysplasia, and/or early onset arthritis. Stickler syndrome type I (ocular form) is caused by mutation in the COL2A1 gene. Ptosis and uveitis are relatively rare ophthalmological manifestations of this syndrome. We report an Indian boy having 2710C>T mutation in COL2A1 gene demonstrating short stature, ptosis, and uveitis with Stickler syndrome. PMID:28018693

  16. Crigler-Najjar syndrome type I in a Turkish newborn caused by a novel mutation and Gilbert type genetic defect.

    PubMed

    Yildiz, D; Alan, S; Kilic, A; Yaman, A; Erdeve, O; Kuloglu, Z; Atasay, B; Arsan, S

    2013-01-01

    Crigler-Najjar syndrome (CNS), caused by deficiency of bilirubin uridine diphosphate glucuronosyltransferase (UGT) 1A1, is a rare and autosomal recessive inherited disorder characterized by severe unconjugated nonhemolytic hyperbilirubinemia since birth. We present a girl with CNS type I caused by a novel mutation and Gilbert type genetic defect. Gilbert's Syndrome (GS) and CNS type I both involve abnormalities in bilirubin conjugation secondary to deficiency of bilirubin UGT. The combined defects even in benign genetic forms were shown to cause more serious clinical disease. The patient has been treated with daily home-based phototherapy for more than nine months and considered as a candidate for liver transplantation.

  17. Sirenomelia: a new type, showing VACTERL association with Thomas syndrome and a review of literature.

    PubMed

    Lhuaire, Martin; Jestin, Agnès; Boulagnon, Camille; Loock, Mélanie; Doco-Fenzy, Martine; Gaillard, Dominique; Diebold, Marie-Danièle; Avisse, Claude; Labrousse, Marc

    2013-03-01

    Sirenomelia or "mermaid syndrome" is a rare congenital anomaly known since antiquity. This congenital anomaly is defined as a polymalformative syndrome that associates major muscle and skeleton abnormalities (unique lower limbs) with visceral abnormalities (unilateral or bilateral renal agenesis, anomalies of the abdominal vascularisation). This phenotype, typical of sirenomelia syndrome, may be more or less severe. The pathogenic mechanisms of this syndrome are still debated and its etiology remains unknown. We report here a new type of sirenomelia that we observed in a fetus belonging to the collection of the Department of Anatomy of Reims, which led us to perform a comprehensive review of the literature on the subject: this type has never been reported and cannot be classified according to the Stocker and Heifetz classification. Moreover, this case also presents a VACTERL association with Thomas syndrome.

  18. The pathogenesis of the clinical features of oral-facial-digital syndrome type I

    PubMed Central

    AlKattan, Wael M.; Al-Qattan, Mohammad M.; Bafaqeeh, Sameer A.

    2015-01-01

    Oral-facial-digital syndrome type I (OFDI) is an X-linked syndrome, which has several craniofacial and limb features; and hence, patients frequently present to craniofacial and plastic surgeons. Oral-facial-digital syndrome type I is caused by mutations in the CXORF5 gene. The gene product is one of the basal body proteins of a slim microtubule-based organelle called the “primary cilium”. Most of the clinical features of OFDI patients are related to dysfunctions of the primary cilium leading to abnormal Hedgehog signal transduction, depressed planar cell polarity pathway, and errors in cell cycle control. PMID:26593159

  19. Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage.

    PubMed

    Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

    2011-01-01

    Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency.

  20. A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis

    PubMed Central

    Baab, Karen L.; Brown, Peter; Falk, Dean; Richtsmeier, Joan T.; Hildebolt, Charles F.; Smith, Kirk; Jungers, William

    2016-01-01

    The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots

  1. A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis.

    PubMed

    Baab, Karen L; Brown, Peter; Falk, Dean; Richtsmeier, Joan T; Hildebolt, Charles F; Smith, Kirk; Jungers, William

    2016-01-01

    The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots

  2. A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy.

    PubMed

    Okamoto, Nobuhiko; Toribe, Yasuhisa; Nakajima, Tohru; Okinaga, Takeshi; Kurosawa, Kenji; Nonaka, Ikuya; Shimokawa, Osamu; Matsumoto, Noamichi

    2002-01-01

    Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene -/- mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.

  3. Influence of coffee brew in metabolic syndrome and type 2 diabetes.

    PubMed

    Abrahão, Sheila Andrade; Pereira, Rosemary Gualberto Fonseca Alvarenga; de Sousa, Raimundo Vicente; Lima, Adriene Ribeiro; Crema, Gabriela Previatti; Barros, Bianca Sacramento

    2013-06-01

    This study aimed to evaluate the effect of coffee drinking on clinical markers of diabetes and metabolic syndrome in Zucker rats. Diabetic Zucker rats with metabolic syndrome and control Zucker rats were used for in vivo tests. The animals received daily doses of coffee drink by gavage for 30 days. After the treatment, the levels of glucose, triglycerides, total cholesterol and fractions, creatinine, uric acid, activity of aspartate aminotransferase and alanine aminotransferase were evaluated. Urea and creatinine levels were also analyzed in urine. By collaborating in the modulation of the metabolic syndrome and diabetes mellitus type 2, coffee drink helped in reducing serum glucose, total cholesterol and triglycerides. The results demonstrate that treatment with roasted coffee drink, because of its hypoglycemic and hypolipidemic effect, is efficient in the protection of animals with metabolic syndrome and diabetes mellitus type 2.

  4. Do you know this syndrome? Type 2 benign symmetric lipomatosis (Launois-Bensaude)*

    PubMed Central

    Esposito, Ana Cláudia Cavalcante; Munhoz, Tania; Abbade, Luciana Patrícia Fernandes; Miot, Hélio Amante

    2016-01-01

    A 57-year-old female showed bulky, loose tumors, which progressively spread to her arms, anterior chest, and back. She reported dysphagia and dyspnea after mild exertion. She denied alcohol consumption. CT scan of her chest showed no internal lesions. Benign symmetric lipomatosis is a rare syndrome, clinically described as multiple nonencapsulated lipomas of various sizes and symmetrical distribution. This syndrome has three known phenotypes; in type 2 (Launois-Bensaude syndrome), lesions occur primarily on the shoulders, upper arms, and chest, and is unrelated to alcoholism. It causes aesthetic deformities and might block the upper airways. Mediastinal invasion might occur as well. PMID:28099616

  5. Four systems involved with congenital abnormalities: a new type of syndromic hearing loss - ADOC Wang's syndrome?

    PubMed

    Wang, Qiuju; Zhao, Fei-Fan; Shi, Yong-Bing

    2011-10-01

    Syndromic hearing impairment encompasses hundreds of phenotypes. We identified a young female patient affected by the unique combination of dysplasia of the auricular system, patent ductus arteriosus (PDA), choroideremia, and enamel hypoplasia. The patient was treated with PDA ligature and left exploratory tympanotomy. Impairment in all four systems suggests a correlation with the neural crest. It is presumed that all of the features result from the same origin, probably through autosomal recessive inheritance or a novel mutation during the embryonic period. When audio-dento-oculo-cardio systems are involved, we suggest that this new syndrome can be named 'ADOC Wang's syndrome', summarizing the disorders of the four systems and indicative of the founding person (Dr Wang, the first and corresponding author of the paper).

  6. Dilated perivascular spaces: an informative radiologic finding in Sanfilippo syndrome type A.

    PubMed

    Kara, Simay; Sherr, Elliott H; Barkovich, A James

    2008-05-01

    Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is a lysosomal storage disorder caused by deficiency of heparan N-sulfamidase, resulting in defective degradation and subsequent storage of heparan sulfate. It is characterized by progressive nervous system involvement. Cribriform changes in the corpus callosum, basal ganglia, and white matter, diffuse high-intensity signal in the white matter, and cerebral atrophy have been described in patients with this disorder. This case report describes a child with Sanfilippo syndrome type A who exhibited fairly mild clinical findings but an unusual magnetic resonance imaging pattern that included multiple moderate-sized cysts (probably enlarged perivascular spaces) within the corpus callosum and an abnormal appearance of the clivus and cervical vertebrae. This case calls attention to the variety of appearances possible with magnetic resonance imaging in Sanfilippo syndrome type A.

  7. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type.

    PubMed

    Malfait, Fransiska; Wenstrup, Richard J; De Paepe, Anne

    2010-10-01

    Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. It comprises Ehlers-Danlos syndrome type I and Ehlers-Danlos syndrome type II, but it is now apparent that these form a continuum of clinical findings and differ only in phenotypic severity. It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the α1 and the α2-chain of type V collagen, respectively. However, because no prospective molecular studies of COL5A1 and COL5A2 have been performed in a clinically well-defined patient group, this number may underestimate the real proportion of patients with classic Ehlers-Danlos syndrome harboring a mutation in one of these genes. In the majority of patients with molecularly characterized classic Ehlers-Danlos syndrome, the disease is caused by a mutation leading to a nonfunctional COL5A1 allele and resulting in haploinsufficiency of type V collagen. A smaller proportion of patients harbor a structural mutation in COL5A1 or COL5A2, causing the production of a functionally defective type V collagen protein. Most mutations identified so far result in a reduced amount of type V collagen in the connective tissues available for collagen fibrillogenesis. Inter- and intrafamilial phenotypic variability is observed, but no genotype-phenotype correlations have been observed. No treatment for the underlying defect is presently available for Ehlers-Danlos syndrome. However, a series of preventive guidelines are applicable.

  8. Waardenburg syndrome type I with heterochromia iridis and circumscribed hypopigmentation of the skin.

    PubMed

    Eigelshoven, Sibylle; Kameda, Gitta; Kortüm, Anne-Katrin; Hübsch, Simone; Angerstein, Wolfgang; Singh, Preeti; Vöhringer, Renate; Goecke, Timm; Mayatepek, Ertan; Ruzicka, Thomas; Wildhardt, Gabriele; Meissner, Thomas; Kruse, Roland

    2009-01-01

    We report a 3-year-old girl with autosomal dominant inherited Waardenburg syndrome type I showing circumscribed hypopigmentation of the skin, heterochromia iridis, sensorineural deafness, and dental aberrations. Clinical diagnosis was confirmed by the identification of an underlying missense mutation (C811T) in the PAX3 gene. Early diagnosis of Waardenburg syndrome among children with pigment anomalies enables a successful interdisciplinary medical care.

  9. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the pre-Columbian culture of Colombia.

    PubMed

    Pachajoa, Harry; Rodriguez, Carlos Armando

    2014-01-01

    Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo-Ecuadorian Pacific coast of the Tumaco-Tolita culture.

  10. X-linked albinism-deafness syndrome and Waardenburg syndrome type II: A hypothesis

    SciTech Connect

    Zlotogora, J.

    1995-11-20

    Margolis reported on a large pedigree with a {open_quotes}new{close_quotes} X-linked syndrome of profound deafness and albinism (MIM 300700, albinism-deafness syndrome). The affected males presented with profound deafness and severe pigmentary abnormalities of the skin. At birth the skin appeared as almost albinotic except for areas of light pigmentation over the gluteal and scrotal areas, and thereafter pigmentation gradually increased over the body. Skin changes ultimately included areas of hypopigmentation and spots of hyperpigmentation. Some of the affected males also had blue irides, heterochromia, or segmental color iris changes. In carrier females, variable hearing impairment was documented without any pigmentary changes. 9 refs., 1 fig.

  11. Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits synthesis of type I interferons (IFNs) in infected pigs and in cultured cells. Here we report that one PRRSV mutant A2MC2 induces type I IFNs in cultured cells and has no effect on IFN downstream signaling. The mutant isolate was p...

  12. Relationship between Fatigue and Gait Abnormality in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

    ERIC Educational Resources Information Center

    Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Albertini, Giorgio; Camerota, Filippo

    2012-01-01

    Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The…

  13. Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes

    PubMed Central

    Malik, Vasanti S.; Popkin, Barry M.; Bray, George A.; Després, Jean-Pierre; Willett, Walter C.; Hu, Frank B.

    2010-01-01

    OBJECTIVE Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed. RESEARCH DESIGN AND METHODS We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes. RESULTS Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1–2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or <1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12–1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02–1.42]. CONCLUSIONS In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases. PMID:20693348

  14. A data-driven method for syndrome type identification and classification in traditional Chinese medicine.

    PubMed

    Zhang, Nevin Lianwen; Fu, Chen; Liu, Teng Fei; Chen, Bao-Xin; Poon, Kin Man; Chen, Pei Xian; Zhang, Yun-Ling

    2017-03-01

    The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

  15. Demographic and clinical correlates of metabolic syndrome in Native African type-2 diabetic patients.

    PubMed Central

    Isezuo, S. A.; Ezunu, E.

    2005-01-01

    OBJECTIVES: To describe the metabolic syndrome and its demographic and clinical correlates in native African type-2 diabetic patients. METHODS: Cross-sectional analysis of 254 type-2 diabetic indigenous Nigerians consecutively recruited in a teaching hospital. The main outcome measure was metabolic syndrome. Variables of interest included family history/duration of diabetes mellitus and hypertension, gender, socioeconomic class, occupation and place of domicile (urban or rural). Intergroup comparisons were made with Chi-squared tests or t-tests. RESULTS: Patients were aged 35-80 years (mean: 52.0 +/- 11.7 years) and made of 154 (60.6%) males and 100 (39.4%) females. Full-blown metabolic syndrome was noted in 52 patients (20.5%). Metabolic syndrome, as defined by the WHO, was noted in 150 patients (59.1%). About 72.4% of patients were dyslipidemic, 54.3% were hypertensive, 42.5% were obese, 44.9% were microalbuminuric and 32.3% were hyperuricemic. Ischemic heart disease (myocardial infarction) occurred in only 2.4% of patients. Concurrent hypertension and dyslipidemia; obesity and dyslipidemia; and hypertension and obesity occurred in 44.4%, 42.5% and 33.1% of type-2 diabetics, respectively. Compared to the diabetics without metabolic syndrome, those with the syndrome had a significantly higher proportion of patients with a family history of hypertension and diabetes (44% versus 25%; p = 0.003); among the upper/middle socioeconomic class: 52.0% versus 30.8% (p = 0.001); and among the urban dwelling: 68.0% versus 49.0% (p = 0.004). Metabolic syndrome was inversely proportional to the physical activity of an individual (chi2 = 21.69, df = 5, p = 0.001). Blood pressure was significantly higher among patients with metabolic syndrome than those without it (140.6 +/- 22.9/85.2 +/- 12.9 mmHg versus 126.9 +/- 15.4 mmHg; P < 0.01). CONCLUSIONS: The development of metabolic syndrome in African type-2 diabetic patients is influenced by demographic and clinical factors

  16. Electrocardiogram in Andersen-Tawil syndrome. New electrocardiographic criteria for diagnosis of type-1 Andersen-Tawil syndrome.

    PubMed

    Kukla, Piotr; Biernacka, Elzbieta K; Baranchuk, Adrian; Jastrzebski, Marek; Jagodzinska, Michalina

    2014-08-01

    Andersen - Tawil syndrome (ATS) is an autosomal - dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis, and distinctive facial and skeletal dysmorphism. Mutations in KCNJ2, which encodes the α-subunit of the potassium channel Kir2.1, were identified in patients with ATS. This genotype has been designated as type-1 ATS (ATS1). KCNJ2 mutations are detectable in up to 60 % of patients with ATS. Cardiac manifestations of ATS include frequent premature ventricular contractions (PVC), Q-U interval prolongation, prominent U-waves, and a special type of polymorphic ventricular tachycardia (PMVT) called bidirectional ventricular tachycardia (BiVT). The presence of frequent PVCs at rest are helpful in distinguishing ATS from typical catecholaminergic polymorphic ventricular tachycardia (CPVT). In typical CPVT, rapid PMVT and BiVT usually manifest during or after exercising. Additionally, CPVT or torsade de pointes in LQTS are faster, very symptomatic causing syncope or often deteriorate into VF resulting in sudden cardiac death. PVCs at rest are quite frequent in ATS1 patients, however, in LQTS patients, PVCs and asymptomatic VT are uncommon which also contributes to differentiating them. The article describes the new electrocardiographic criteria proposed for diagnosis of type-1 Andersen-Tawil syndrome. A differential diagnosis between Andersen-Tawil syndrome, the catecholamine polymorphic ventiruclar tachycardia and long QT syndrome is depicted. Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1.

  17. Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

    PubMed

    Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

    2011-11-01

    Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia.

  18. Comparison of Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Modified Live Vaccines against Heterologous Type 1 and Type 2 PRRSV Challenge in Growing Pigs

    PubMed Central

    Kim, Taeyeon; Park, Changhoon; Choi, Kyuhyung; Jeong, Jiwoon; Kang, Ikjae; Park, Su-Jin

    2015-01-01

    The objective of the present study was to compare the efficacy of two commercial type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live vaccines against heterologous type 1 and type 2 PRRSV challenge in growing pigs. Vaccination with a type 1 PRRSV vaccine reduced the level of viremia after type 1 PRRSV challenge but did not reduce the level of viremia after the type 2 PRRSV challenge in pigs. Increased levels of interleukin-10 (IL-10) stimulated by type 2 PRRSV coincided with the low numbers of type 2 PRRSV-specific interferon gamma-secreting cells (IFN-γ-SC) in vaccinated pigs after type 2 PRRSV challenge, whereas low levels of IL-10 stimulated by type 1 PRRSV coincided with high numbers of type 1 PRRSV-specific IFN-γ-SC in vaccinated pigs after type 1 PRRSV challenge. Additionally, vaccination with the type 1 PRRSV vaccine effectively reduced the lung lesions and type 1 PRRSV nucleic acids in type 1 PRRSV-challenged pigs but did not reduce lung lesions and type 2 PRRSV nucleic acids in type 2 PRRSV-challenged pigs. There were no significant differences between two commercial type 1 PRRSV vaccines against type 1 and type 2 PRRSV challenge based on virological results, immunological responses, and pathological outcomes. This study demonstrates that vaccinating pigs with the type 1 PRRSV vaccine provides partial protection against respiratory disease with heterologous type 1 PRRSV challenge but no protection with heterologous type 2 PRRSV challenge. PMID:25855554

  19. Digenic mutations involving both the BSND and GJB2 genes detected in Bartter syndrome type IV.

    PubMed

    Wang, Hong-Han; Feng, Yong; Li, Hai-Bo; Wu, Hong; Mei, Ling-Yun; Wang, Xing-Wei; Jiang, Lu; He, Chu-Feng

    2017-01-01

    Bartter syndrome type IV, characterized by salt-losing nephropathies and sensorineural deafness, is caused by mutations of BSND or simultaneous mutations of both CLCNKA and CLCNKB. GJB2 is the primary causative gene for non-syndromic sensorineural deafness and associated with several syndromic sensorineural deafness. Owing to the rarity of Bartter syndrome, only a few mutations have been reported in the abovementioned causative genes. To investigate the underlying mutations in a Chinese patient with Bartter syndrome type IV, genetic analysis of BSND, CLCNKA, CLCNKB and GJB2 were performed by polymerase chain reaction and direct sequencing. Finally, double homozygous mutations c.22C > T (p.Arg8Trp) and c.127G > A (Val43Ile) were detected in exon 1 of BSND. Intriguingly, compound heterozygous mutations c.235delC (p.Leu79CysfsX3) and c.109G > A (p.Val37Ile) were also revealed in exon 2 of GJB2 in the same patient. No pathogenic mutations were found in CLCNKA and CLCNKB. Our results indicated that the homozygous mutation c.22C > T was the key genetic reason for the proband, and a digenic effect of BSND and GJB2 might contributed to sensorineural deafness. To our knowledge, it was the first report showing that the GJB2 gene mutations were detected in Bartter syndrome.

  20. Genetic influences on type 2 diabetes and metabolic syndrome related quantitative traits in Mauritius.

    PubMed

    Jowett, Jeremy B; Diego, Vincent P; Kotea, Navaratnam; Kowlessur, Sudhir; Chitson, Pierrot; Dyer, Thomas D; Zimmet, Paul; Blangero, John

    2009-02-01

    Epidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P= .12), however a significant increase in waist circumference was observed in these groups (P= .02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits.

  1. [Chronic type A aortic dissection associated with Turner syndrome; report of a case].

    PubMed

    Tanaka, Hideyuki; Kozaki, Tomofumi; Kume, Masazumi; Miyamoto, Shinji

    2014-12-01

    Aortic dissection is a critical but rare complication of Turner syndrome. This report describes a case of chronic aortic dissection in a patient with Turner syndrome. A 54-year-old woman, suffering from mild back pain for 1 month, was referred to our hospital with a diagnosis of Stanford type A chronic aortic dissection and a bicuspid aortic valve with moderate regurgitation. Computed tomography revealed aortic dissection, involving all arch branches, extending from the ascending to the abdominal aorta. The true lumen of the brachial artery was nearly obstructed by the thrombosed false lumen. Elective aortic arch repair and aortic valve replacement were successfully performed. The patient was diagnosed with 45, XO Turner syndrome after surgery. Taking aortopathy of Turner syndrome into consideration, surveillance of the residual aorta was performed. No rapidly progressive dilatation of the residual aorta was detected during the 6 years' follow-up.

  2. Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1.

    PubMed

    Yoshimura, Hidekane; Iwasaki, Satoshi; Nishio, Shin-Ya; Kumakawa, Kozo; Tono, Tetsuya; Kobayashi, Yumiko; Sato, Hiroaki; Nagai, Kyoko; Ishikawa, Kotaro; Ikezono, Tetsuo; Naito, Yasushi; Fukushima, Kunihiro; Oshikawa, Chie; Kimitsuki, Takashi; Nakanishi, Hiroshi; Usami, Shin-Ichi

    2014-01-01

    Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

  3. ClC-K chloride channels: emerging pathophysiology of Bartter syndrome type 3.

    PubMed

    Andrini, Olga; Keck, Mathilde; Briones, Rodolfo; Lourdel, Stéphane; Vargas-Poussou, Rosa; Teulon, Jacques

    2015-06-15

    The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature. All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism, but Bartter syndrome type 3 has the most heterogeneous presentation, extending from severe to very mild. A relatively large number of CLCNKB mutations have been reported, including gene deletions and nonsense or missense mutations. However, only 20 CLCNKB mutations have been functionally analyzed, due to technical difficulties regarding ClC-Kb functional expression in heterologous systems. This review provides an overview of recent progress in the functional consequences of CLCNKB mutations on ClC-Kb chloride channel activity. It has been observed that 1) all ClC-Kb mutants have an impaired expression at the membrane; and 2) a minority of the mutants combines reduced membrane expression with altered pH-dependent channel gating. Although further investigation is needed to fully characterize disease pathogenesis, Bartter syndrome type 3 probably belongs to the large family of conformational diseases, in which the mutations destabilize channel structure, inducing ClC-Kb retention in the endoplasmic reticulum and accelerated channel degradation.

  4. [Case of Sanfilippo syndrome type B and Wilson disease born to unrelated parents].

    PubMed

    Takaura, Natsuko; Tanaka, Akemi; Yoshida, Toshiko; Takeshita, Yukiko; Shimizu, Norikazu; Aoki, Tsugutoshi; Tamai, Hiroshi; Yamano, Tsunekazu

    2006-01-01

    A 5-year-old boy visited a hospital because of macrocephalus, mental retardation and hepatic dysfunction, and was suspected to have Wilson's disease since his father had this disease. The serum level of ceruloplasmin was low, but urinary copper excretion was not increased markedly. He was treated with D-penicillamine. He was then reffered to our hospital because of his facial features suggesting mucopolysaccharidosis. Based on mucopolysacchariduria and the deficiency of N-acetylglucosaminidase, the diagnosis of Sanfilippo syndrome type B was made. Molecular analyses identified him as a compound heterozygote for both the ATP7B (A844V/2659delG) and alpha-N-acetylglucosaminidase (V241M/R482W) genes, responsible for Wilson's disease and Sanfilippo syndrome type B, respectively. Although born to non-consanguineous parents, he had two rare autosomal recessive diseases. In this case, liver dysfunction was attributed to Wilson's disease, and mental retardation to Sanfilippo syndrome.

  5. Incidence, Mortality and Positive Predictive Value of Type 1 Cardiorenal Syndrome in Acute Coronary Syndrome

    PubMed Central

    Pimienta González, Raquel; Couto Comba, Patricia; Rodríguez Esteban, Marcos; Alemán Sánchez, José Juan; Hernández Afonso, Julio; Rodríguez Pérez, María del Cristo; Marcelino Rodríguez, Itahisa; Brito Díaz, Buenaventura; Elosua, Roberto; Cabrera de León, Antonio

    2016-01-01

    Objectives To determine whether the risk of cardiovascular mortality associated with cardiorenal syndrome subtype 1 (CRS1) in patients who were hospitalized for acute coronary syndrome (ACS) was greater than the expected risk based on the sum of its components, to estimate the predictive value of CRS1, and to determine whether the severity of CRS1 worsens the prognosis. Methods Follow-up study of 1912 incident cases of ACS for 1 year after discharge. Cox regression models were estimated with time to event (in-hospital death, and readmission or death during the first year after discharge) as the dependent variable. Results The incidence of CRS1 was 9.2/1000 person-days of hospitalization (95% CI = 8.1–10.5), but these patients accounted for 56.6% (95% CI = 47.4–65.) of all mortality. The positive predictive value of CRS1 was 29.6% (95% CI = 23.9–36.0) for in-hospital death, and 51.4% (95% CI = 44.8–58.0) for readmission or death after discharge. The risk of in-hospital death from CRS1 (RR = 18.3; 95% CI = 6.3–53.2) was greater than the sum of risks associated with either acute heart failure (RR = 7.6; 95% CI = 1.8–31.8) or acute kidney injury (RR = 2.8; 95% CI = 0.9–8.8). The risk of events associated with CRS1 also increased with syndrome severity, reaching a RR of 10.6 (95% CI = 6.2–18.1) for in-hospital death at the highest severity level. Conclusions The effect of CRS1 on in-hospital mortality is greater than the sum of the effects associated with each of its components, and it increases with the severity of the syndrome. CRS1 accounted for more than half of all mortality, and its positive predictive value approached 30% in-hospital and 50% after discharge. PMID:27907067

  6. The association between macronutrient intake and the metabolic syndrome and its components in type 1 diabetes.

    PubMed

    Ahola, Aila J; Harjutsalo, Valma; Thorn, Lena M; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik

    2017-02-20

    Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.

  7. Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes.

    PubMed

    Lodish, Maya B; Stratakis, Constantine A

    2010-06-01

    Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes.

  8. A case of Feingold type 2 syndrome associated with keratoconus refines keratoconus type 7 locus on chromosome 13q.

    PubMed

    Sirchia, Fabio; Di Gregorio, Eleonora; Restagno, Gabriella; Grosso, Enrico; Pappi, Patrizia; Talarico, Flavia; Savin, Elisa; Cavalieri, Simona; Giorgio, Elisa; Mancini, Cecilia; Pasini, Barbara; Mehta, Jodhbir S; Brusco, Alfredo

    2017-04-01

    We report on a 58-year old woman with microcephaly, mild dysmorphic features, bilateral keratoconus, digital abnormalities, short stature and mild cognitive delay. Except for keratoconus, the phenotype was suggestive for Feingold syndrome type 2 (FGLDS2, MIM 614326), a rare autosomal dominant disorder described in six patients worldwide, due to the haploinsufficiency of MIR17HG, a micro RNA encoding gene. Karyotype showed a de novo deletion on chromosome 13q, further defined by array-Comparative Genomic Hybridization (a-CGH) to a 17.2-Mb region. The deletion included MIR17HG, as expected by the FGLDS2 phenotype, and twelve genes from the keratoconus type 7 locus. Because our patient presented with keratoconus, we propose she further refines disease genes at this locus. Among previously suggested candidates, we exclude DOCK9 and STK24, and propose as best candidates IPO5, DNAJC3, MBNL2 and RAP2A. In conclusion, we report a novel phenotypic association of Feingold syndrome type 2 and keratoconus, a likely contiguous gene syndrome due to a large genomic deletion on 13q spanning MIR17HG and a still to be identified gene for keratoconus.

  9. Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Hagspiel, Klaus D.; Bonatti, Hugo; Sabri, Saher; Arslan, Bulent; Harthun, Nancy L.

    2011-04-15

    Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

  10. Cinnamon: Potential Role in the Prevention of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes

    PubMed Central

    Qin, Bolin; Panickar, Kiran S.; Anderson, Richard A.

    2010-01-01

    Metabolic syndrome is associated with insulin resistance, elevated glucose and lipids, inflammation, decreased antioxidant activity, increased weight gain, and increased glycation of proteins. Cinnamon has been shown to improve all of these variables in in vitro, animal, and/or human studies. In addition, cinnamon has been shown to alleviate factors associated with Alzheimer's disease by blocking and reversing tau formation in vitro and in ischemic stroke by blocking cell swelling. In vitro studies also show that components of cinnamon control angiogenesis associated with the proliferation of cancer cells. Human studies involving control subjects and subjects with metabolic syndrome, type 2 diabetes mellitus, and polycystic ovary syndrome all show beneficial effects of whole cinnamon and/or aqueous extracts of cinnamon on glucose, insulin, insulin sensitivity, lipids, antioxidant status, blood pressure, lean body mass, and gastric emptying. However, not all studies have shown positive effects of cinnamon, and type and amount of cinnamon, as well as the type of subjects and drugs subjects are taking, are likely to affect the response to cinnamon. In summary, components of cinnamon may be important in the alleviation and prevention of the signs and symptoms of metabolic syndrome, type 2 diabetes, and cardiovascular and related diseases. PMID:20513336

  11. Prospective Study of the Prevalence of Alzheimer-Type Dementia in Institutionalized Individuals with Down Syndrome.

    ERIC Educational Resources Information Center

    Visser, F. E.; And Others

    1997-01-01

    Institutionalized patients with Down syndrome (N=307) were monitored for 5 to 10 years to determine prevalence of Alzheimer-type dementia. Prevalence increased from 11% between ages 40 and 49 to 77% between 60 and 69. All patients 70 and over had dementia. Mean age of onset of dementia was 56 years. Neuropathological findings were consistent with…

  12. Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

    PubMed

    Gripp, K W; Stolle, C A; McDonald-McGinn, D M; Markowitz, R I; Bartlett, S P; Katowitz, J A; Muenke, M; Zackai, E H

    1998-07-24

    We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis.

  13. Glucose Transporter Type 1 Deficiency Syndrome with Carbohydrate-Responsive Symptoms but without Epilepsy

    ERIC Educational Resources Information Center

    Koy, Anne; Assmann, Birgit; Klepper, Joerg; Mayatepek, Ertan

    2011-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by a defect in glucose transport across the blood-brain barrier. The main symptoms are epilepsy, developmental delay, movement disorders, and deceleration of head circumference. A ketogenic diet has been shown to be effective in controlling epilepsy in GLUT1-DS. We report a female…

  14. Psychosocial Implications of Usher Syndrome, Type I, throughout the Life Cycle.

    ERIC Educational Resources Information Center

    Miner, I. D.

    1995-01-01

    Usher syndrome, Type I, requires multiple adaptations throughout the life cycle because each stage of life has tasks and losses associated with deafness and progressive retinitis pigmentosa. This article examines the issues raised at each stage, using clinical vignettes from persons who have this condition and their families. (Author/DB)

  15. Genomic sequence and virulence comparison of four type 2 porcine reproductive and respiratory syndrome virus strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a ubiquitous and costly virus that exhibits substantial sequence and virulence disparity among diverse isolates. In this study, we compared the whole genomic sequence and virulence of 4 North American Type 2 PRRSV isolates. Among the 4 i...

  16. A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain.

    PubMed

    Rodríguez-Soriano, Juan; Vallo, Alfredo; Pérez de Nanclares, Gustavo; Bilbao, José Ramón; Castaño, Luis

    2005-07-01

    The term "Bartter syndrome" encompasses a group of closely related inherited tubulopathies characterized by markedly reduced NaCl transport by the distal nephron. At present, five different genetic variants have been demonstrated. The majority of patients with so-called classic Bartter syndrome carry inactivating mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel (Bartter syndrome type III). The purpose of this study was to investigate the underlying mutation in cases of classic Bartter syndrome followed at our center. Ten patients, including two sisters, with clinical and biochemical features of classic Bartter syndrome were included in the mutational analysis. They originated from different regions of Spain with either Basque or Spanish ancestry. There was no history of consanguineous marriage in any of the kindreds. The parents and siblings of each patient, as well as a population of 300 healthy control adult subjects, were also analyzed. All ten patients were found to be homozygous for an identical missense mutation in the CLCNKB gene, substituting a threonine for an alanine at codon 204 (A204T) in the putative fifth transmembrane domain of the protein. None of the 300 control subjects were homozygous for the A204T allele. Overall, the A204T mutation was detected on 2/600 control chromosomes. Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms to severe growth retardation. Demonstration of a point mutation within the CLCNKB gene as the apparently unique cause of Bartter syndrome type III in Spain is highly suggestive of a founder effect. Our results also support the lack of correlation between genotype and phenotype in this disease.

  17. Canagliflozin improves risk factors of metabolic syndrome in patients with type 2 diabetes mellitus and metabolic syndrome

    PubMed Central

    Davies, Michael J; Merton, Katherine W; Vijapurkar, Ujjwala; Balis, Dainius A; Desai, Mehul

    2017-01-01

    Objective Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP) in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome. Methods This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1) and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2). Changes from baseline in glycemic efficacy, anthropometric measures, BP, and lipids were evaluated with canagliflozin versus glimepiride and sitagliptin at week 52 in patients who met ≥2 of the criteria for metabolic syndrome (in addition to T2DM): triglycerides ≥1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L (men) or <1.3 mmol/L (women); waist circumference ≥102 cm (non-Asian men), ≥88 cm (non-Asian women), >90 cm (Asian men), or >80 cm (Asian women); diagnosis of hypertension or meeting BP-related criteria (systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg). Safety was assessed based on adverse event reports. Results In study 1, canagliflozin 100 and 300 mg provided similar and greater HbA1c reductions versus glimepiride, respectively. In study 2, canagliflozin 300 mg provided greater HbA1c lowering versus sitagliptin 100 mg. Canagliflozin also reduced fasting plasma glucose, body weight, body mass index, waist circumference, BP, and triglycerides, and increased HDL-C and low-density lipoprotein cholesterol versus glimepiride and sitagliptin. Canagliflozin was generally well tolerated in each study. Conclusion Canagliflozin was associated with improvements in all components of metabolic syndrome in patients with T2DM and

  18. Pfeiffer syndrome type 2: further delineation and review of the literature.

    PubMed

    Plomp, A S; Hamel, B C; Cobben, J M; Verloes, A; Offermans, J P; Lajeunie, E; Fryns, J P; de Die-Smulders, C E

    1998-01-23

    We present 5 unrelated patients, 3 boys and 2 girls, with Pfeiffer syndrome (PS) type 2. They all had cloverleaf skull, severe proptosis, ankylosis of the elbows, broad thumbs and/or broad halluces and variable accompanying anomalies. We review the literature on all subtypes of PS. Most patients with PS type 2 died shortly after birth. Causes of death include pulmonary problems, brain abnormalities, prematurity and post-operative complications. DNA studies were performed in 3 of the 5 patients. Two of them showed a 1036T --> C mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, that was earlier reported in PS and in Crouzon syndrome. Probably most, if not all, PS type 2 cases are caused by a de novo mutation in the FGFR2 gene or in another, yet unidentified gene. To date all type 2 cases have been non-familial. A low recurrence risk for parents can be advised.

  19. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.

  20. Exploration of Differences in Types of Sleep Disturbance and Severity of Sleep Problems between Individuals with Cri du Chat Syndrome, Down's Syndrome, and Jacobsen Syndrome: A Case Control Study

    ERIC Educational Resources Information Center

    Maas, Anneke P. H. M.; Didden, Robert; Korzilius, Hubert; Curfs, Leopold M. G.

    2012-01-01

    The prevalence of sleep problems in individuals with intellectual disability (ID) seems to vary between genetic syndromes associated with ID. Different types of sleep disturbances may indicate underlying causes of sleep problems and these types of sleep disturbances may vary between different genetic syndromes. We examined and compared five types…

  1. Unusual manifestations of ectodermal dysplasia-syndactyly syndrome type I in two Yemeni siblings.

    PubMed

    Mohammad, Alshami

    2015-01-15

    Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by malformations of tissues derived from the ectoderm, including the skin, its appendages (hair, nails, sweat glands), teeth, and the breasts. Ectodermal dysplasia syndactyly syndrome (EDSS) is a rare, newly described type of ED involving syndactyly. We report 2 Yemeni siblings with typical EDSS manifestations, including bilateral, partial cutaneous syndactyly of the fingers and toes; sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and conical, widely spaced teeth with enamel notches. In addition, the siblings presented with other features hitherto not described for this syndrome, such as adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples, hypoplastic thumbs, and red scalp hair.

  2. Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child

    PubMed Central

    Gera, D. N.; Ghuge, P. P.; Gandhi, S.; Vanikar, A. V.; Shrimali, J. D.; Kute, V. B.; Trivedi, H. L.

    2013-01-01

    Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors. PMID:24339527

  3. Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child.

    PubMed

    Gera, D N; Ghuge, P P; Gandhi, S; Vanikar, A V; Shrimali, J D; Kute, V B; Trivedi, H L

    2013-11-01

    Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors.

  4. Type III Klippel-Feil syndrome: case report and review of associated craniofacial anomalies.

    PubMed

    Naikmasur, Venkatesh G; Sattur, Atul P; Kirty, R N; Thakur, Arpita Rai

    2011-07-01

    Klippel-Feil syndrome (KFS) is a complex syndrome of osseous and visceral anomalies that include the classical clinical triad of short neck, limitation of head and neck movements and low posterior hairline. It may also be associated with anomalies of the genitourinary, musculoskeletal, neurologic and cardiac systems. We report a case of type III KFS with associated rib anomalies such as cervical rib, fusion and bifid ribs, scoliosis and fused crossed renal ectopia. The aim of this paper was to summarize all craniofacial anomalies that occur in association with KFS, so that clinicians would be aware of them during diagnosis and treatment planning.

  5. Mouse model of Sanfilippo syndrome type B: relation of phenotypic features to background strain.

    PubMed

    Gografe, Sylvia I; Garbuzova-Davis, Svitlana; Willing, Alison E; Haas, Ken; Chamizo, Wilfredo; Sanberg, Paul R

    2003-12-01

    Sanfilippo syndrome type B or mucopolysaccharidosis type III B (MPS IIIB) is a lysosomal storage disorder that is inherited in autosomal recessive manner. It is characterized by systemic heparan sulfate accumulation in lysosomes due to deficiency of the enzyme alpha-N-acetylglucosaminidase (Naglu). Devastating clinical abnormalities with severe central nervous system involvement and somatic disease lead to premature death. A mouse model of Sanfilippo syndrome type B was created by targeted disruption of the gene encoding Naglu, providing a powerful tool for understanding pathogenesis and developing novel therapeutic strategies. However, the JAX GEMM Strain B6.129S6-Naglutm1Efn mouse, although showing biochemical similarities to humans with Sanfilippo syndrome, exhibits aging and behavioral differences. We observed idiosyncrasies, such as skeletal dysmorphism, hydrocephalus, ocular abnormalities, organomegaly, growth retardation, and anomalies of the integument, in our breeding colony of Naglu mutant mice and determined that several of them were at least partially related to the background strain C57BL/6. These background strain abnormalities, therefore, potentially mimic or overlap signs of the induced syndrome in our mice. Our observations may prove useful in studies of Naglu mutant mice. The necessity for distinguishing background anomalies from signs of the modeled disease is apparent.

  6. Radiographic and Tomographic Analysis in Patients with Stickler Syndrome Type I

    PubMed Central

    Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Kenis, Vladimir; Zandieh, Shahin; Hofstaetter, Jochen G; Klaushofer, Klaus; Grill, Franz

    2013-01-01

    Objective: To further investigate the underlying pathology of axial and appendicular skeletal abnormalities such as painful spine stiffness, gait abnormalities, early onset osteoarthritis and patellar instability in patients with Stickler syndrome type I. Radiographic and tomographic analyses were organized. Methods: From a series of Stickler syndrome patients followed from early life to late childhood. Ten patients (6 boys and four girls of different ethnic origins were consistent with the diagnosis of Stickler syndrome type I ). Phenotypic characterization was the baseline tool applied for all patients and genotypic correlation was performed on four families Results: A constellation of axial abnormalities namely; anterolateral ossification of the anterior longitudinal spinal ligament with subsequent fusion of two cervical vertebrae, early onset Forestier disease (progressive spinal hyperostosis with subsequent vertebral fusion on top of bridging osteophytes and “Bamboo-like spine” resembling ankylosing spondylitis) and severe premature spine degeneration were evident. Appendicular abnormalities in connection with generalized epiphyseal dysplasia were the underlying aetiology in patients with Intoeing gait and femoral anteversion, early onset severe osteoarthritis of the weight bearing joint. Remarkable trochleo-patellar dysplasia secondary to severe osteoarthritis causing effectively the development of patellar instability was additional pathology. Mutation of COL2A1 has been confirmed as the causative gene for Stickler syndrome type I Conclusion: We concluded that conventional radiographs and the molecular determination of a COL2A1 in patients with (Stickler syndrome type I) are insufficient tools to explain the reasons behind the tremendous magnitude of axial and appendicular skeletal abnormalities. We were able to modify the criteria of the clinical phenotype as designated by Rose et al in accordance with the novel axial and appendicular criteria as

  7. Fenofibrate treatment in two adults with Crigler-Najjar syndrome type II.

    PubMed

    Yilmaz, Serif; Dursun, Mehmet; Canoruç, Fikri; Kidir, Veysel; Beştaş, Remzi

    2006-03-01

    Crigler-Najjar syndrome type II is a rare familial disorder of bilirubin conjugation with consecutive life-long unconjugated hyperbilirubinemia. In the presence of severe hyperbilirubinemia, a fetus or an adult is at risk for neurological defects in this syndrome. This paper is the first report emphasizing details about this disorder in two patients from Turkey. The diagnosis was made on the basis of history and laboratory findings excluding other causes of unconjugated hyperbilirubinemia. Phenobarbital loading test and C bile analysis also supported the diagnosis. There was a study in the literature in which treatment with chlofibrate had been recommended in this syndrome. Based on the results of that study, we administered fenofibrate treatment to our patients for one month and analyzed serum bilirubin levels before and after this procedure. No improvement in bilirubin levels was observed in either case.

  8. Autoimmune hepatitis type 2 arising in PFAPA syndrome: coincidences or possible correlations?

    PubMed

    Della Corte, Claudia; Ranucci, Giusy; Tufano, Maria; Alessio, Maria; Iorio, Raffaele

    2010-03-01

    PFAPA syndrome is a chronic disease classified in the group of autoinflammatory syndromes characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis in young children. The etiology of this disorder is still unknown, but a primary dysfunction of the innate immune system seems to be involved. According to Marshall criteria, it is not possible to diagnose PFAPA in the presence of autoimmune diseases. We present here the case report of an 8-month girl with PFAPA who developed autoimmune hepatitis type 2 at the age of 18 months. We suppose that the dysregulation in innate immunity that is typical of patients with PFAPA could trigger autoimmune disorders such as autoimmune hepatitis in susceptible subjects. The possible relationships between immune-system dysfunction peculiar to this syndrome and autoimmune hepatitis are discussed.

  9. Type and frequency of cardiac defects in embryofetal alcohol syndrome. Report of 16 cases.

    PubMed Central

    Löser, H; Majewski, F

    1977-01-01

    Within a period of 3 years, 56 infants and children with embryofetal alcohol syndrome have been detected and examined for heart defects. All children were from mothers who had been addicted to alcohol even during pregnancy and they showed a typical pattern of malformations, as described by Lemoine et al. (1968) and Jones et al. (1973). In 16 cases cardiovascular malformations were confirmed by heart catheterisation or pathological examination. The overall incidence of heart defects in this syndrome was 29 per cent. The incidence rises to nearly 50 per cent in the more severe types of this syndrome. Atrial septal defects were found to be the most common heart defect (10 out of 16 cases); ventricular septal defects and other variable malformations occurred less frequently. The high incidence of heart defects indicates that alcoholism during pregnancy has to be considered as a serious and preventable cause of congenital heart disease. Images PMID:603740

  10. Genetic influences on type 2 diabetes and metabolic syndrome related quantitative traits in Mauritius

    PubMed Central

    Jowett, Jeremy B.; Diego, Vincent P.; Kotea, Navaratnam; Kowlessur, Sudhir; Chitson, Pierrot; Dyer, Thomas D.; Zimmet, Paul; Blangero, John

    2009-01-01

    Epidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P=0.119), however a significant increase in waist circumference was observed in these groups (P=0.02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius Family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits. PMID:19210179

  11. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes

    PubMed Central

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Vargas, Guadalupe; Gonzalez, Baldomero; Isibasi, Armando; Archundia-Riveros, Irma; Mendoza, Victoria

    2015-01-01

    Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. PMID:26273680

  12. Burnout Syndrome Among Health Care Students: The Role of Type D Personality.

    PubMed

    Skodova, Zuzana; Lajciakova, Petra; Banovcinova, Lubica

    2016-07-18

    The aim of this study was to examine the effect of Type D personality, along with other personality traits (resilience and sense of coherence), on burnout syndrome and its counterpart, engagement, among students of nursing, midwifery, and psychology. A cross-sectional study was conducted on 97 university students (91.9% females; M age = 20.2 ± 1.49 years). A Type D personality subscale, School Burnout Inventory, Utrecht Work Engagement Scale, Sense of Coherence Questionnaire, and Baruth Protective Factor Inventory were used. Linear regression models, Student's t test, and Pearson's correlation analysis were employed. Negative affectivity, a dimension of Type D personality, was a significant personality predictor for burnout syndrome (β = .54; 95% CI = [0.33, 1.01]). The only significant personality predictor of engagement was a sense of coherence. Students who were identified as having Type D personality characteristics scored significantly higher on the burnout syndrome questionnaire (t = -2.58, p < .01). In health care professions, personality predictors should be addressed to prevent burnout.

  13. Knowledge, assessment, and management of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type among Flemish physiotherapists.

    PubMed

    Rombaut, Lies; Deane, Janet; Simmonds, Jane; De Wandele, Inge; De Paepe, Anne; Malfait, Fransiska; Calders, Patrick

    2015-03-01

    Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS-HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists' knowledge of JHS/EDS-HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty-five Flemish physiotherapists participated in the study by filling out electronically a modified version of the "Hypermobility and Hypermobility Syndrome Questionnaire" (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS-HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS-HT. Knowledge of hypermobility and JHS/EDS-HT is weak, especially regarding the features associated with JHS/EDS-HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS-HT is under-recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed.

  14. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report.

    PubMed

    Hu, Soo-Young; Choi, Jin-Gyu; Son, Byung-Chul

    2015-10-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia.

  15. [Preliminary study on syndrome differentiation types and acupuncture for whiplash injuries].

    PubMed

    Chen, Ye-meng; Li, Hui; Zheng, Xin; Zhang, Qun-ce; Wang, Tian-fang

    2011-04-01

    Whiplash injury is a relatively common injury of clinical acupuncture and moxibustion in the United States. The mechanism and clinical manifestation of whiplash injuries as well as its pathogenesis described in TCM were analyzed in this present article. The authors introduced the TCM syndrome differentiation of whiplash injuries and claimed that both the location and the stage of disease should be considered. For the different injury locations, the meridian musculature differentiation was applied to classify the whiplash injuries as Taiyang, Yangming, Shaoyang and Shaoyin Meridian syndromes. Considering the duration of the injury, qi stagnation and blood stasis types were classified in the acute stage and phlegm accumulation, insufficiency of the liver and kidney and qi and blood deficiencies types were classified during the chronic stage. An acupuncture protocol for whiplash injuries and typical cases were also introduced.

  16. Cerebro-fronto-facial syndrome type 3 with polymicrogyria: a clinical presentation of Baraitser-Winter syndrome.

    PubMed

    Eker, Hatice Koçak; Derinkuyu, Betül Emine; Ünal, Sevim; Masliah-Planchon, Julien; Drunat, Séverine; Verloes, Alain

    2014-01-01

    Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum.

  17. The role of narrative medicine in the management of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Knight, Isobel

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a hereditary connective tissue disorder affecting every bodily system. It is largely underdiagnosed by many practitioners, with the result of a considerable delay in diagnosis and, consequently, in the onset of adequate management schedule and treatment. Patients may also experience to be misbelieved, erroneously considered affected by a psychiatric or psychosomatic disorders, and rejected by the medical profession, which can lead to feelings of anger and resentment. Patient journeys are often long and complicated, but if doctors allowed the patient time to tell the full story, and were more prepared to think holistically, there may be a far more positive outcome. Here, the patients' perspective is presented with a narrative medicine approach, illustrating the tri-dimensional experience of a JHS/EDS-HT patient, who is also a Bowen Practitioner and a medical writer/educator. Narrative medicine would be invaluable in working with JHS/EDS-HT so that the patient can tell the story, and offer the practitioner a whole picture of her/his suffering and, often, the key for understanding the cause(s). Once this has been achieved, it might be possible to build upon a more positive and therapeutic dialogue which would result in better treatment and more effective management. It is also important for doctors to communicate with JHS/EDS-HT experts who will ultimately improve the patient journey and treatment outcomes of such a complex connective tissue disorder.

  18. Crigler-Najjar syndrome type 2: Novel UGT1A1 mutation

    PubMed Central

    Nair, Karippoth Mohandas; Lohse, Peter; Nampoothiri, Sheela

    2012-01-01

    Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation. PMID:23162302

  19. Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome.

    PubMed

    Encha Razavi, F; Larroche, J C; Roume, J; Gonzales, M; Kondo, H C; Mulliez, N

    1996-03-01

    We report on a distinct pattern of primary central nervous system (CNS) degeneration affecting neuronal survival in the brain and spinal cord in 5 fetuses with fetal akinesia sequence (FAS). This neuropathological pattern is characteristic of a lethal entity that we propose calling type III lissencephaly syndrome. Parental consanguinity and the recurrence in sibs support a genetic cause. The mechanism of neuronal death is not yet understood; abnormal apoptosis and/or deficiency in neurotropic factors may be considered possible causes.

  20. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  1. A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1

    PubMed Central

    Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo

    2016-01-01

    Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. PMID:27081571

  2. Transplantation of human umbilical cord blood cells benefits an animal model of Sanfilippo syndrome type B.

    PubMed

    Garbuzova-Davis, Svitlana; Willing, Alison E; Desjarlais, Tammy; Davis Sanberg, Cyndy; Sanberg, Paul R

    2005-08-01

    Sanfilippo syndrome type B is caused by alpha-N-acetylglucosaminidase (Naglu) enzyme deficiency leading to an accumulation of undegraded heparan sulfate, a glycosaminoglycan (GAG). Cell therapy is a promising new treatment and human umbilical cord blood (hUCB) cell transplantation may be preferred for delivery of the missing enzyme. We investigated the ability of mononuclear hUCB cells administered into the lateral cerebral ventricle to ameliorate/prevent histopathological changes in mice modeling Sanfilippo syndrome type B. These are the first results supporting enzyme replacement by administered hUCB cells. In vivo, transplanted hUCB cells survived long-term (7 months), migrated into the parenchyma of the brain and peripheral organs, expressed neural antigens, and exhibited neuron and astrocyte-like morphology. Transplant benefits were also demonstrated by stable cytoarchitecture in the hippocampus and cerebellum, and by reduced GAGs in the livers of treated mutant mice. A hUCB cell transplant may be an effective therapeutic strategy for enzyme delivery in Sanfilippo syndrome type B.

  3. Different impacts of metabolic syndrome components on insulin resistance in type 2 diabetes.

    PubMed

    Hsu, Chung-Hua

    2013-01-01

    Objective. To examine the different impacts of MS components on insulin resistance in type 2 diabetes. Methods. A number of subjects (144) who met the criteria of (1) age between 30 and 75 years, (2) had type 2 diabetes for more than one year, and (3) taking gliclazide and metformin for more than 6 months were enrolled. All subjects were assigned to one of the four HOMA index categories. The HOMA index quartile 4 denotes the highest insulin resistance. The main outcome evaluated is the odds ratios (ORs) of different MS components on HOMA index quartile 4. The characteristics in HOMA index quartiles and groups of nonmetabolic syndrome (NMS; number of components < 2), metabolic syndrome A (MSA; number of components = 2), and metabolic syndrome B (MSB; number of components > 2) were also evaluated. Results. The results showed that both MSA and MSB groups had higher ORs (5.9 and 13.8 times, resp.) than the NMS group; and that subjects with large waist circumference (LWC) and high triglyceride (HTG) level have higher ORs (6.1 and 2.6 times, resp.) in developing higher insulin resistance than normal control subjects. Conclusion. Type 2 diabetic patients with greater number of MS components have higher ORs in developing increased insulin resistance.

  4. Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

    PubMed

    Castori, M; Morlino, S; Sana, M E; Paradisi, M; Tadini, G; Angioni, A; Malacarne, M; Grammatico, P; Iascone, M; Forzano, F

    2016-08-01

    Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema.

  5. Timing and Type of Alcohol Consumption and the Metabolic Syndrome - ELSA-Brasil

    PubMed Central

    Vieira, Bruna Angelo; Luft, Vivian Cristine; Schmidt, Maria Inês; Chambless, Lloyd Ellwood; Chor, Dora; Barreto, Sandhi Maria; Duncan, Bruce Bartholow

    2016-01-01

    The prevalence of the metabolic syndrome is rising worldwide. Its association with alcohol intake, a major lifestyle factor, is unclear, particularly with respect to the influence of drinking with as opposed to outside of meals. We investigated the associations of different aspects of alcohol consumption with the metabolic syndrome and its components. In cross-sectional analyses of 14,375 active or retired civil servants (aged 35–74 years) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we fitted logistic regression models to investigate interactions between the quantity of alcohol, the timing of its consumption with respect to meals, and the predominant beverage type in the association of alcohol consumption with the metabolic syndrome. In analyses adjusted for age, sex, educational level, income, socioeconomic status, ethnicity, smoking, body mass index, and physical activity, light consumption of alcoholic beverages with meals was inversely associated with the metabolic syndrome (≤4 drinks/week: OR = 0.85, 95%CI 0.74–0.97; 4 to 7 drinks/week: OR = 0.75, 95%CI 0.61–0.92), compared to abstention/occasional drinking. On the other hand, greater consumption of alcohol consumed outside of meals was significantly associated with the metabolic syndrome (7 to 14 drinks/week: OR = 1.32, 95%CI 1.11–1.57; ≥14 drinks/week: OR = 1.60, 95%CI 1.29–1.98). Drinking predominantly wine, which occurred mostly with meals, was significantly related to a lower syndrome prevalence; drinking predominantly beer, most notably when outside of meals and in larger quantity, was frequently associated with a greater prevalence. In conclusion, the alcohol—metabolic syndrome association differs markedly depending on the relationship of intake to meals. Beverage preference—wine or beer—appears to underlie at least part of this difference. Notably, most alcohol was consumed in metabolically unfavorable type and timing. If further investigations

  6. Timing and Type of Alcohol Consumption and the Metabolic Syndrome - ELSA-Brasil.

    PubMed

    Vieira, Bruna Angelo; Luft, Vivian Cristine; Schmidt, Maria Inês; Chambless, Lloyd Ellwood; Chor, Dora; Barreto, Sandhi Maria; Duncan, Bruce Bartholow

    2016-01-01

    The prevalence of the metabolic syndrome is rising worldwide. Its association with alcohol intake, a major lifestyle factor, is unclear, particularly with respect to the influence of drinking with as opposed to outside of meals. We investigated the associations of different aspects of alcohol consumption with the metabolic syndrome and its components. In cross-sectional analyses of 14,375 active or retired civil servants (aged 35-74 years) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we fitted logistic regression models to investigate interactions between the quantity of alcohol, the timing of its consumption with respect to meals, and the predominant beverage type in the association of alcohol consumption with the metabolic syndrome. In analyses adjusted for age, sex, educational level, income, socioeconomic status, ethnicity, smoking, body mass index, and physical activity, light consumption of alcoholic beverages with meals was inversely associated with the metabolic syndrome (≤4 drinks/week: OR = 0.85, 95%CI 0.74-0.97; 4 to 7 drinks/week: OR = 0.75, 95%CI 0.61-0.92), compared to abstention/occasional drinking. On the other hand, greater consumption of alcohol consumed outside of meals was significantly associated with the metabolic syndrome (7 to 14 drinks/week: OR = 1.32, 95%CI 1.11-1.57; ≥14 drinks/week: OR = 1.60, 95%CI 1.29-1.98). Drinking predominantly wine, which occurred mostly with meals, was significantly related to a lower syndrome prevalence; drinking predominantly beer, most notably when outside of meals and in larger quantity, was frequently associated with a greater prevalence. In conclusion, the alcohol-metabolic syndrome association differs markedly depending on the relationship of intake to meals. Beverage preference-wine or beer-appears to underlie at least part of this difference. Notably, most alcohol was consumed in metabolically unfavorable type and timing. If further investigations extend these

  7. Combined tarsal and carpal tunnel syndrome in mucolipidosis type III. A case study and review.

    PubMed

    Smuts, Izelle; Potgieter, Denise; van der Westhuizen, Francois Hendrikus

    2009-01-01

    Mucolipidosis type III (MLIII) (MIM# 252600) is an uncommon autosomal recessive disorder that results from uridine 5'-diphosphate-N-acetylglucosamine: lysosomal hydrolase N-acetyl-1-phosphotransferase or UDP-GlcNAc 1-phosphotransferase deficiency. Clinical manifestations include developmental delay, short stature and other structural abnormalities. Less common clinical features, such as carpal tunnel syndrome, claw hand deformities, trigger fingers, and claw toes have previously been reported, but no specific association with tarsal tunnel syndrome has been reported in the literature. Tarsal tunnel syndrome is caused by entrapment of the posterior tibialis nerve in the tunnel formed by the medial malleolus of the ankle and the flexor retinaculum. It causes pain in the heel and sole of the foot as well as abnormal sensation in the distribution area of nervus tibialis posterior. In adults, the most common cause described is a ganglion. The phenomenon is rare in children and the published series are small. This case report portrays the presentation of a young girl with breath-holding spells secondary to painful bilateral tarsal tunnel syndrome and trigger fingers subsequently diagnosed with MLIII.

  8. Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

    ERIC Educational Resources Information Center

    Mazzocco, Michele M. M.

    2001-01-01

    This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

  9. Addison's disease in a patient with hypothyroidism: autoimmune polyglandular syndrome type 2.

    PubMed

    Bain, Anna; Stewart, Munro; Mwamure, Peter; Nirmalaraj, Kingsley

    2015-08-03

    A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection.

  10. A Case of Carbonic Anhydrase Type 2 Deficiency Syndrome with Autistic Disorder

    PubMed Central

    KILIÇ, Birim Günay; UĞUR, Çağatay; SADAY DUMAN, Nagihan; AKÇAKIN, Melda

    2014-01-01

    Carbonic Anhydrase Type II Deficiency Syndrome (CADS) is a disease with an autosomal recessive inheritance that mainly includes characteristics of osteopetrosis, renal tubular acidosis and cerebral calcification. Pathological fractures, poor vision due to cranial nerve pressure, wide forehead, disproportionate mouth and jaw, physical and mental developmental delay are other features. In this paper, we present the case of a patient who was referred to our department with a diagnosis of CADS and diagnosed with autistic disorder after a psychiatric evaluation. We performed a detailed literature search, however, we did not find any report of co-existence of CADS (osteopetrosis intermediate type) and autistic disorder.

  11. Successful management of complex regional pain syndrome type 1 using single injection interscalene brachial plexus block

    PubMed Central

    Fallatah, Summayah M.A.

    2014-01-01

    Complex regional pain syndrome (CRPS) type 1 of the upper limb is a painful and debilitating condition. Interscalene brachial plexus block (ISB) in conjugation with other modalities was shown to be a feasible therapy with variable success. We reported a case of CRPS type 1 as diagnosed by International Association for the Study of Pain criteria in which pharmacological approaches failed to achieve adequate pain relief and even were associated with progressive dysfunction of the upper extremity. Single injection ISB, in combination with physical therapy and botulinum toxin injection, was successful to alleviate pain with functional restoration. PMID:25422619

  12. Wild-type microglia arrest pathology in a mouse model of Rett syndrome.

    PubMed

    Derecki, Noël C; Cronk, James C; Lu, Zhenjie; Xu, Eric; Abbott, Stephen B G; Guyenet, Patrice G; Kipnis, Jonathan

    2012-03-18

    Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction. However, as shown recently, glia, specifically astrocytes, also contribute to Rett pathophysiology. Here we examine the role of another form of glia, microglia, in a murine model of Rett syndrome. Transplantation of wild-type bone marrow into irradiation-conditioned Mecp2-null hosts resulted in engraftment of brain parenchyma by bone-marrow-derived myeloid cells of microglial phenotype, and arrest of disease development. However, when cranial irradiation was blocked by lead shield, and microglial engraftment was prevented, disease was not arrested. Similarly, targeted expression of MECP2 in myeloid cells, driven by Lysm(cre) on an Mecp2-null background, markedly attenuated disease symptoms. Thus, through multiple approaches, wild-type Mecp2-expressing microglia within the context of an Mecp2-null male mouse arrested numerous facets of disease pathology: lifespan was increased, breathing patterns were normalized, apnoeas were reduced, body weight was increased to near that of wild type, and locomotor activity was improved. Mecp2(+/-) females also showed significant improvements as a result of wild-type microglial engraftment. These benefits mediated by wild-type microglia, however, were diminished when phagocytic activity was inhibited pharmacologically by using annexin V to block phosphatydilserine residues on apoptotic targets, thus preventing recognition and engulfment by tissue-resident phagocytes. These results suggest the importance of microglial phagocytic activity in Rett syndrome. Our data implicate microglia as major players in the pathophysiology of this devastating disorder, and suggest that bone marrow transplantation might offer a feasible therapeutic approach for it.

  13. Sudden death in type 1 diabetes: the mystery of the 'dead in bed' syndrome.

    PubMed

    Tu, Emily; Twigg, Stephen M; Semsarian, Christopher

    2010-01-07

    Sudden cardiac death is an unpredictable and devastating event, particularly in the young. A significant proportion of sudden deaths in the young are unexplained-no cause is identified either during life or at post-mortem. This is seen in a subgroup of young patients with type 1 diabetes who have dead in bed syndrome, where these victims are in good health, retire to bed, only to be found dead the following morning in a bed which is undisturbed, suggesting no terminal struggle or seizure. The underlying cause of dead in bed syndrome remains unknown, but is likely to be due to a terminal malignant arrhythmia. A plausible hypothesis is that it may be secondary to QT interval prolongation (followed by a degenerate ventricular tachycardia), caused by a number of factors including acute hypoglycaemia, on a background of cardiac autonomic neuropathy, and possible genetic influences. It is envisaged that understanding the causes and triggers of dead in bed syndrome will allow appropriate therapeutic interventions to be initiated in high-risk patients with type 1 diabetes, with the ultimate goal to prevent sudden death.

  14. A Case of Acute Aortic Dissection Type B Associated with Cushing's Syndrome

    PubMed Central

    Petramala, Luigi; Cotesta, Dario; Sapienza, Paolo; Zinnamosca, Laura; Moroni, Enrico; di Marzio, Luca; De Toma, Giorgio; Letizia, Claudio

    2009-01-01

    We report a case of a 63-year-old man, with a previous history of hypertension and glucose intolerance associated troncular obesity that was emergently admitted to our Institution for evaluation of a severe, constant posterior chest pain which radiated anteriorly and dyspnoea with a suspected diagnosis of acute aortic dissection. A CT scan of thorax and abdomen demonstrated a dissection starting just below left succlavian artery and extending downward to the left renal artery, involving the celiac tripod and superior mesenteric artery. The dissection was classified as Stanford B, De Bakey III. Moreover, CT scan of abdomen revealed incidentally a left adrenal tumor of 25 mm of diameter. An emergent prosthetic graft was placed just below the origin of the left succlavian artery up-to the diaphragmatic hiatus. Furthermore, a diagnostic evaluation of the mass revealed an increase of cortisol production, and a diagnosis of Cushing's syndrome was done and the patient underwent an adrenalectomy via laparotomic approach. We report an association of acute aortic dissection of acute aortic dissection type B associated to Cushing's syndrome. Keywords Cushing's syndrome; Adrenocortical adenoma; Aortic dissection type B PMID:22505966

  15. Localization of two genes for Usher syndrome type I to chromosome 11

    SciTech Connect

    Smith, R.J.H.; Daiger, S.P. ); Jay, M.; Bird, A. ); Reardon, W. ); Guest, M. ); Kimberling, W.J.; Pelias, M.Z.; Keats, B.J.B.

    1992-12-01

    The Usher syndromes (USH) are autosomal recessive diseases characterized by congenital sensorineural hearing loss and progressive pigmentary retinopathy. While relatively rare in the general population, collectively they account for approximately 6% of the congenitally deaf population. Usher syndrome type II (USH2) has been mapped to chromosome 1q, and one form of Usher syndrome type I (USH1) has been mapped to chromosome 14q. These loci have been excluded as regions of USH genes in this data set, which is composed of 8 French-Acadian USH1 families and 11 British USH1 families. Both of these sets of families show linkage to loci on chromosome 11. Linkage analysis demonstrates locus heterogeneity between these sets of families, with the French-Acadian families showing linkage to D11S419 (Z = 4.20, [theta] = 0) and the British families showing linkage to D11S527 (Z = 6.03, [theta] = 0). Genetic heterogeneity of the data set was confirmed using HOMOG and the M test (log likelihood ratio > 10[sup 5]). These results confirm the presence of two distinct USH1 loci on chromosome 11. 41 refs., 4 figs., 6 tabs.

  16. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B

    PubMed Central

    Godhane, Alkesh; Kalaskar, Ashita; Demble, Swati

    2016-01-01

    ABSTRACT Aglossia is a rare congenital malformation that often occurs as an isolated disorder or is observed in association with other congenital deformities, particularly limb defects. We present a unique case of a 7-year-old girl with aglossia, hypodactyli, rudimentary ears, retrognathic and V-shaped mandible. Her parental history revealed intrauterine exposure of medicines. The patient had problems in difficulty in eating, speech, taste sensation and hearing. The present case does not fit into Hall’s classification of oromandibular limb hypogenesis syndrome (OLHS) which best describes hypoglossia and limb deformities. Therefore, the purpose of this article is to document the rare variant of OLHS which can be included in Hall’s classification. How to cite this article: Kalaskar RR, Godhane A, Kalaskar A, Demble S. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. Int J Clin Pediatr Dent 2016;9(1):78-81. PMID:27274161

  17. Isolated aglossia congenita: A rare case of oromandibular limb hypogenesis syndrome type I B

    PubMed Central

    Gupta, Shalini R

    2012-01-01

    Aglossia congenita (AC), congenital total absence of the tongue, is a very rare midline developmental anomaly, hypothesized to be associated with vascular disruption between the fourth and eighth week of gestation. It was classified by Hall (1971) as part of oromandibular limb hypogenesis syndrome (OLHS) type I B. Most of the cases reported with OLHS are actually hypoglossia with limb abnormalities whereas isolated aglossia is an extremely rare entity. A case of isolated AC is presented in a 28-year-old Indian male. He had long narrow face, tapering chin, low set ears, and microstomia. Intraorally, he had narrow palatal vault, constricted oropharyngeal isthmus, oligodontia, and maxillo-mandibular hypoplasia. Interestingly, the patient showed a median palatal groove, which has not been reported before. He also had an unusual acquired adaptive mechanism to compensate for aglossia. This report presents the manifestations of this rare syndrome, its complications, differential diagnosis, and rehabilitation strategies. PMID:23248477

  18. The subtle signs of Wolfram (DIDMOAD) syndrome: not all juvenile diabetes is type 1 diabetes.

    PubMed

    Boettcher, Claudia; Brosig, Burkhard; Zimmer, Klaus P; Wudy, Stefan A

    2011-01-01

    Wolfram syndrome (also known as DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, deafness) is an autosomal recessive disorder characterized by the association of childhood non-immune insulin-dependent diabetes mellitus (DM) with progressive bilateral optic atrophy. Additional symptoms including signs of severe neurodegeneration and psychiatric illness are likely to evolve over time resulting in premature death. We report on two siblings of Turkish origin from our diabetes clinic who were diagnosed with Wolfram syndrome after 6 years and 2 years duration of DM, respectively. Subtle symptoms such as attitude changes, growing reading difficulties in the history of children or adolescents with antibody negative and ketone negative DM should alert the treating physician and lead to re-evaluation of the diagnosis, keeping in mind that not all juvenile DM is type 1 DM.

  19. Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

    PubMed

    Romani, Marta; Mancini, Francesca; Micalizzi, Alessia; Poretti, Andrea; Miccinilli, Elide; Accorsi, Patrizia; Avola, Emanuela; Bertini, Enrico; Borgatti, Renato; Romaniello, Romina; Ceylaner, Serdar; Coppola, Giangennaro; D'Arrigo, Stefano; Giordano, Lucio; Janecke, Andreas R; Lituania, Mario; Ludwig, Kathrin; Martorell, Loreto; Mazza, Tommaso; Odent, Sylvie; Pinelli, Lorenzo; Poo, Pilar; Santucci, Margherita; Signorini, Sabrina; Simonati, Alessandro; Spiegel, Ronen; Stanzial, Franco; Steinlin, Maja; Tabarki, Brahim; Wolf, Nicole I; Zibordi, Federica; Boltshauser, Eugen; Valente, Enza Maria

    2015-01-01

    Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients.

  20. Ehlers-Danlos Syndrome Type VIII: A Rare Cause of Leg Ulcers in Young Patients

    PubMed Central

    Lucas, Antoine; Piérard, Gérald E.; Hermanns-Lê, Trinh; De Paepe, Anne; Dupuy, Alain

    2013-01-01

    Ehlers-Danlos syndrome type VIII (EDS-VIII) is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII. PMID:24198978

  1. Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus

    PubMed Central

    Mayo, Mary Catherine; Deng, Jane C.; Albores, Jeffrey; Zeidler, Michelle; Harper, Ronald M.; Avidan, Alon Y.

    2015-01-01

    We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis. Citation: May MC, Deng JC, Albores J, Zeidler M, Harper RM, Avidan AY. Hypocretin deficiency associated with narcolepsy type 1 and central hypoventilation syndrome in neurosarcoidosis of the hypothalamus. J Clin Sleep Med 2015;11(9):1063–1065. PMID:25979096

  2. Anesthetic management of a parturient with type III Klippel-Feil syndrome.

    PubMed

    Hsu, G; Manabat, E; Huffnagle, S; Huffnagle, H J

    2011-01-01

    Klippel-Feil syndrome is believed to occur from failure of normal segmentation of cervical somites during gestation. We present the case of a 38-year-old primiparous woman with type III Klippel-Feil syndrome for elective cesarean delivery. Our patient had a short webbed neck, short stature, limited neck flexion and extension, and thoraco-lumbar abnormalities. A multidisciplinary approach, involving obstetrics, medical subspecialties, anesthesiology, otolaryngology, and radiology, were utilized to evaluate and manage this patient. Pulmonary function testing revealed a restrictive defect, but transthoracic echocardiography was normal without pulmonary hypertension. We planned a combined spinal-epidural technique; however, only the epidural technique was obtained. Cesarean delivery was commenced with favorable maternal and fetal outcomes. Post-operative pain management was provided with intravenous morphine patient-controlled analgesia.

  3. Effector mechanisms of the autoimmune syndrome in the murine model of Autoimmune Polyglandular Syndrome Type

    PubMed Central

    DeVoss, Jason J.; Shum, Anthony K.; Johannes, Kellsey P.A.; Lu, Wen; Krawisz, Anna K.; Wang, Peter; Yang, Ting; LeClair, Norbert P.; Austin, Cecilia; Strauss, Erich C.; Anderson, Mark S.

    2008-01-01

    Mutations in the Autoimmune regulator (Aire) gene result in a clinical phenomenon known as Autoimmune Polyglandular Syndrome Type I (APS1), which classically manifests as a triad of adrenal insufficiency, hypoparathyroidism, and chronic mucocutaneous infections. In addition to this triad, a number of other autoimmune diseases have been observed in APS1 patients including Sjögren's syndrome, vitiligo, alopecia, uveitis, and others. Aire-deficient mice, the animal model for APS1, have highlighted the role of the thymus in the disease process and demonstrated a failure in central tolerance in aire-deficient mice. However, autoantibodies have been observed against multiple organs in both mice and humans, making it unclear what the specific role of B and T cells are in the pathogenesis of disease. Utilizing the aire-deficient mouse as a preclinical model for APS1, we have investigated the relative contribution of specific lymphocyte populations, with the goal of identifying the cell populations which may be targeted for rational therapeutic design. Here we show that T cells are indispensable to the breakdown of self-tolerance, in contrast to B cells which play a more limited role in autoimmunity. Th1 polarized CD4+ T cells, in particular, are major contributors to the autoimmune response. With this knowledge, we go on to utilize therapies targeted at T cells to investigate their ability to modulate disease in vivo. Depletion of CD4+ T cells using a neutralizing antibody ameliorated the disease process. Thus, therapies targeted specifically at the CD4+ T cell subset may help control autoimmune disease in patients with APS1. PMID:18768863

  4. Unexpected association between joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type and obsessive-compulsive personality disorder.

    PubMed

    Pasquini, Massimo; Celletti, Claudia; Berardelli, Isabella; Roselli, Valentina; Mastroeni, Simona; Castori, Marco; Biondi, Massimo; Camerota, Filippo

    2014-05-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a largely unrecognized, heritable connective tissue disorder, mainly characterized by joint instability complications, widespread musculoskeletal pain, and minor skin features. In a case-control study, 47 consecutive JHS/EDS-HT patients were investigated for the prevalence of psychiatric disorders and compared to 45 healthy controls in a single center. The psychiatric evaluation consisted of structured clinical interview for DSM-IV criteria by using the SCID-I and the SCID-II. Symptom severity was assessed using the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), and the Brief Psychiatric Rating Scale (BPRS). The Global Assessment of Functioning Scale (GAF) was used to assess the overall severity of psychological, social, and occupational functions. JHS/EDS-HT patients had significantly higher mean scores for all questionnaires: HAM-A (6.7 vs. 3.8), HAM-D (6.4 vs. 2.7), GAF (75.0 vs. 86.1), and BPRS (27.5 vs. 25.6). The JHS/EDS-HT group had a 4.3 higher risk of being affected by any psychiatric disorder, and in particular, a 5.8 higher risk of having a personality disorder. In particular, 5 JHS/EDS-HT suffered from obsessive-compulsive personality disorder with an observed prevalence rate of 10.6 % (3.6-23.1). Psychiatric assessment of JHS/EDS-HT patients showed an extremely high prevalence of personality disorders (21 %), and of Axis-I disorders (38 %), mostly depressive. This study did not confirm the previously reported increased rate of panic disorders in JHS/EDS-HT.

  5. Refining patterns of joint hypermobility, habitus, and orthopedic traits in joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Morlino, Silvia; Dordoni, Chiara; Sperduti, Isabella; Venturini, Marina; Celletti, Claudia; Camerota, Filippo; Colombi, Marina; Castori, Marco

    2017-03-07

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two overlapping heritable disorders (JHS/EDS-HT) recognized by separated sets of diagnostic criteria and still lack a confirmatory test. This descriptive research was aimed at better characterizing the clinical phenotype of JHS/EDS-HT with focus on available diagnostic criteria, and in order to propose novel features and assessment strategies. One hundred and eighty-nine (163 females, 26 males; age: 2-73 years) patients from two Italian reference centers were investigated for Beighton score, range of motion in 21 additional joints, rate and sites of dislocations and sprains, recurrent soft-tissue injuries, tendon and muscle ruptures, body mass index, arm span/height ratio, wrist and thumb signs, and 12 additional orthopedic features. Rough rates were compared by age, sex, and handedness with a series of parametric and non-parametric tools. Multiple correspondence analysis was carried out for possible co-segregations of features. Beighton score and hypermobility at other joints were influenced by age at diagnosis. Rate and sites of joint instability complications did not vary according to age at diagnosis except for soft-tissue injuries. No major difference was registered by sex and dominant versus non-dominant body side. At multiple correspondence analysis, selected features tend to co-segregate in a dichotomous distribution. Dolichostenomelia and arachnodactyly segregated independently. This study pointed out a more protean musculoskeletal phenotype than previously considered according to available diagnostic criteria for JHS/EDS-HT. Our findings corroborated the need for a re-thinking of JHS/EDS-HT on clinical grounds in order to find better therapeutic and research strategies. © 2017 Wiley Periodicals, Inc.

  6. Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Dordoni, Chiara; Morlino, Silvia; Sperduti, Isabella; Ritelli, Marco; Valiante, Michele; Chiarelli, Nicola; Zanca, Arianna; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina

    2015-03-01

    Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT.

  7. Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

    PubMed Central

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina

    2016-01-01

    Joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients. PMID:27518164

  8. Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

    PubMed Central

    Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

    2017-01-01

    Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research. PMID:28286774

  9. Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

    PubMed

    Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

    2017-01-01

    Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

  10. Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I

    PubMed Central

    Jaijo, Teresa; Oshima, Aki; Aller, Elena; Carney, Carol; Usami, Shin-ichi; Kimberling, William J.

    2012-01-01

    Purpose PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. Methods Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. Results Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%). Conclusions Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment. PMID:22815625

  11. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome

    PubMed Central

    Oudesluijs, Grétel; Li, Zhi; Heijsman, Daphne; Hermann, Mark; Willemsen, Rob; Brouwer, Rutger W.W.; Bertoli Avella, Aida; Prinz, Marco; Crow, Yanick J.; Verheijen, Frans W.

    2016-01-01

    Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders. PMID:27325888

  12. Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness.

    PubMed

    Shin, Jeong-Ah; Lee, Jin-Hee; Lim, Sun-Young; Ha, Hee-Sung; Kwon, Hyuk-Sang; Park, Yong-Moon; Lee, Won-Chul; Kang, Moo-Il; Yim, Hyeon-Woo; Yoon, Kun-Ho; Son, Ho-Young

    2013-07-08

    Metabolic syndrome is defined as a cluster of glucose intolerance, hypertension, dyslipidemia and central obesity with insulin resistance as the source of pathogenesis. Although several different combinations of criteria have been used to define metabolic syndrome, a recently published consensus recommends the use of ethnic-specific criteria, including waist circumference as an indicator of central obesity, triglyceride and high-density lipoprotein (HDL) cholesterol as indicators of dyslipidemia, and blood pressure greater than 130/85 mmHg. The definition of dysglycemia, and whether central obesity and insulin resistance are essential components remain controversial. Regardless of the definition, the prevalence of metabolic syndrome is increasing in Western and Asian countries, particularly in developing areas undergoing rapid socioenvironmental changes. Numerous clinical trials have shown that metabolic syndrome is an important risk factor for cardiovascular disease (CVD), type 2 diabetes mellitus and all-cause mortality. Therefore, metabolic syndrome might be useful as a practical tool to predict these two major metabolic disorders. Comprehensive management of risk factors is very important to the improvement of personal and public health. However, recent studies have focused on the role metabolic syndrome plays as a risk factor for CVD; its importance in the prediction of incident diabetes is frequently overlooked. In the present review, we summarize the known evidence supporting metabolic syndrome as a predictor for type 2 diabetes mellitus and CVD. Additionally, we suggest how metabolic syndrome might be useful in clinical practice, especially for the prediction of diabetes.

  13. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    PubMed

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed.

  14. The association of Chiari type III malformation and Klippel-Feil syndrome with mirror movement: a case report.

    PubMed

    Erol, Fatih Serhat; Ucler, Necati; Yakar, Huseyin

    2011-01-01

    Basically Chiari type III malformation is a combination of encephalocele with of brain stem and cerebellar abnormality. Although Klippel-Feil syndrome may be associated with other congenital anomalies, this syndrome is mainly associated with varying degrees of cervical vertebral fusion anomalies. In this study, we reported the association of Chiari type III malformation and Klippel-Feil syndrome with the mirror movement by imaging studies. The main involvement in Chiari type III malformation and Klippel-Feil syndrome is in the craniocervical junction. In such a small area, the emergence of these complex pathologies in our case was remarkable. Our patient had reconstruction surgery of the posterior fossa and his encephalocele was excised successfully. Hydrocephaly and/or deterioration in the functions of other posterior fossa structures have not been seen in the patient's follow-up.

  15. Candidate regions for Waardenburg syndrome type II: Search for a second WS locus

    SciTech Connect

    Nance, W.E.; Pandya, A.; Blanton, S.H.

    1994-09-01

    Waardenburg syndrome is an autosomal dominant disorder characterized by deafness and pigmentary abnormalities such as heterochromia of irides, hypopigmented skin patches, white forlock and premature graying. Clinically the syndrome has been classified into three types. Type II differs from type I in that dystopia canthorum is generally absent, and type III has associated limb anomalies. Recently linkage analysis localized the gene for WSI to chromosome 2q. PAX-3, which is a human analogue of the murine pax-3 locus, maps to this region and mutations in this gene have been found to segregate with WSI. However genetic heterogeneity clearly exists: most if not all WSII families are unlinked to PAX-3 while most if not all WSI cases are linked. We ascertained a four-year-old female child with an interstitial deletion of chromosome 13 who had features of WS including bilateral congenital sensorineural hearing loss, pale blue irides and pinched nostrils as well as hypertelorism microcephaly, bilateral eyelid ptosis, digitalization of thumbs and fifth finger clinodactyly. High resolution chromosomal analysis revealed a de novo interstitial deletion of 13q22-33.2. There was no family history of WS or retardation. A similar deletion in the region of 13q21-32 has been described in a 13-year-old boy with features of WSII. These two cases strongly suggested that this chromosomal region may include a second locus for WS. We have identified eight families with clinical features of WS type I which have been excluded from linkage to the PAX-3 locus. We have typed these families for microsatellite markers spanning chromosome 13. Linkage between WSII and the chromosome 13 markers was excluded in these families. Hirschsprung disease has been associated with WS and it has recently been mapped to chromosome 10q11.2-q21.1. We are currently typing the 8 families for microsatellites in this region.

  16. Griscelli syndrome types 1 and 3: analysis of four new cases and long-term evaluation of previously diagnosed patients.

    PubMed

    Cağdaş, Deniz; Ozgür, Tuba Turul; Asal, Gülten Türkkanı; Tezcan, Ilhan; Metin, Ayşe; Lambert, Nathalie; de Saint Basile, Geneiveve; Sanal, Ozden

    2012-10-01

    Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. Three different types are caused by defects in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, type 2 patients commonly develop hemophagocytic lymphohistiocytosis, and type 3 patients have only partial albinism. While hematopoietic stem cell transplantation is life saving in type 2, no specific therapy is required for types 1 and 3. Patients with GS types 1 and 3 are very rare. To date, only 2 patients with type 3 and about 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. The neurological deficits in Elejalde syndrome were reported as severe neurodevelopmental delay, seizures, hypotonia, and ophthalmological problems including nystagmus, diplopia, and retinal problems. However, none of these patients' clinical progresses were reported. We described here our two new type 1 and two type 3 patients along with the progresses of our previously diagnosed patients with GS types 1 and 3. Our previous patient with GS type I is alive at age 21 without any other problems except severe mental and motor retardation, patients with type 3 are healthy at ages 21 and 24 years having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Since prognosis, treatment options, and genetic counseling markedly differ among different types, molecular characterization has utmost importance in GS.

  17. Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes.

    PubMed

    Bucca, Brian C; Klingensmith, Georgeanna; Bennett, Jeffrey L

    2011-11-01

    Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non-autoimmune type 1 diabetes. The etiology involves a single gene mutation of the wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy, and sensory-neural deafness. Symptoms are initially absent and signs within the posterior segment of the eye are usually the earliest indicator of WS.These cases characterize unusual and poorly described findings of pigmentary maculopathy in WS and illustrate the importance of collaboration between diabetes and eye care providers; especially in cases of non-autoimmune type 1 diabetes exhibiting atypical human leukocyte-associated antigen haplotypes.

  18. Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome.

    PubMed

    Kim, Jeong Gyun; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Jeong Eun

    2014-02-01

    Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

  19. Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

    PubMed Central

    Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun

    2014-01-01

    Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803

  20. Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage

    PubMed Central

    Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H. Zafer; Polat, Yılmaz; Osmanoglu, Gokhan; Aygar, Muhittin; Ciftciler, A. Erdinc; Parlak, Omer

    2016-01-01

    Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests. PMID:27293947

  1. A multiparametric computational algorithm for comprehensive assessment of genetic mutations in mucopolysaccharidosis type IIIA (Sanfilippo syndrome).

    PubMed

    Ugrinov, Krastyu G; Freed, Stefan D; Thomas, Clayton L; Lee, Shaun W

    2015-01-01

    Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo syndrome) is a Lysosomal Storage Disease caused by cellular deficiency of N-sulfoglucosamine sulfohydrolase (SGSH). Given the large heterogeneity of genetic mutations responsible for the disease, a comprehensive understanding of the mechanisms by which these mutations affect enzyme function is needed to guide effective therapies. We developed a multiparametric computational algorithm to assess how patient genetic mutations in SGSH affect overall enzyme biogenesis, stability, and function. 107 patient mutations for the SGSH gene were obtained from the Human Gene Mutation Database representing all of the clinical mutations documented for Sanfilippo syndrome. We assessed each mutation individually using ten distinct parameters to give a comprehensive predictive score of the stability and misfolding capacity of the SGSH enzyme resulting from each of these mutations. The predictive score generated by our multiparametric algorithm yielded a standardized quantitative assessment of the severity of a given SGSH genetic mutation toward overall enzyme activity. Application of our algorithm has identified SGSH mutations in which enzymatic malfunction of the gene product is specifically due to impairments in protein folding. These scores provide an assessment of the degree to which a particular mutation could be treated using approaches such as chaperone therapies. Our multiparametric protein biogenesis algorithm advances a key understanding in the overall biochemical mechanism underlying Sanfilippo syndrome. Importantly, the design of our multiparametric algorithm can be tailored to many other diseases of genetic heterogeneity for which protein misfolding phenotypes may constitute a major component of disease manifestation.

  2. Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B

    SciTech Connect

    Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

    1988-06-01

    The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

  3. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

    PubMed

    Wimalawansa, Sunil J

    2016-09-20

    The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH)2D3, especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and (G

  4. Clinical variability of type 1 neurofibromatosis: is there a neurofibromatosis-Noonan syndrome?

    PubMed Central

    Stern, H J; Saal, H M; Lee, J S; Fain, P R; Goldgar, D E; Rosenbaum, K N; Barker, D F

    1992-01-01

    Detailed clinical, ophthalmological, and molecular studies were performed on a multigeneration family in which there were many subjects with type 1 neurofibromatosis, a common autosomal dominant disorder. Affected family members displayed a wide range of clinical findings including, in two subjects, features seen in Noonan syndrome (triangular facies, downward slanting palpebral fissures, micrognathia, short stature, and learning disability). Subjects have been described previously whose features have overlapped with neurofibromatosis and Noonan syndrome, and it has been suggested that these persons might represent a separate condition. DNA haplotype analysis showed linkage of the neurofibromatosis phenotype seen in this family to the proximal long arm of chromosome 17 in the region where the type 1 neurofibromatosis gene has been mapped. These results imply that the Noonan phenotype seen in some patients with type 1 neurofibromatosis might be the result of variable or variant expression of the neurofibromatosis gene on chromosome 17. The possible role of non-specific factors, such as fetal hypotonia, in producing the neurofibromatosis-Noonan phenotype needs further investigation. The availability of closely linked and intragenic molecular markers for neurofibromatosis could potentially be useful in the diagnosis and characterisation of patients and families with atypical forms of neurofibromatosis. Images PMID:1348094

  5. Clinical expression in Pfeiffer syndrome type 2 and 3: surveillance in Japan.

    PubMed

    Koga, Hiroshi; Suga, Naohiro; Nakamoto, Takato; Tanaka, Koichi; Takahashi, Noboru

    2012-10-01

    Pfeiffer syndrome (PS) is a classic type of craniosynostosis syndrome. Severe cases usually require emergency care at birth. However, early diagnosis is often precluded by the rarity and consequent low awareness of this disease. This study aimed to clarify phenotypic expressions useful for the diagnosis of PS. We reviewed all cases of PS type 2 or 3 according to Cohen's classification that were reported between 1980 and 2011 in Japan. Clinical and genetic information were extracted from the patients' medical records. A total of 23 patients with PS type 2 or 3 were identified. All 23 patients presented with craniosynostosis, midface hypoplasia, proptosis, broad thumbs, and wide great toes. FGFR2 mutations were confirmed in all 8 patients in whom genetic analyses were performed. In addition to classic symptoms, elbow ankylosis and sacrococcygeal defects were present in 70% and 30% of the patients, respectively. During an average follow-up of 22 months, 22% of patients died before 1 year of age. Elbow ankylosis and sacrococcygeal defects were the phenotypic features recognizable at a glance. These defects strongly suggest the presence of PS in newborns with craniosynostosis.

  6. [Sjögren syndrome associated with renal tubular acidosis type I].

    PubMed

    Górriz, L; Molino, R; Arjona, D; Estripeaut, D

    2000-01-01

    Primary Sjögren's Syndrome complicated with a renal tubular acidosis type 1 and hypocalcemic paralysis, as the principal clinical manifestation, is uncommon. Although the initial manifestations of the nephropathy are not well understood, it is believed that the invasion of mononuclear cells and the high level of circulating antibodies, play an important role in the pathogenesis of the disease. We present a patient with hypocalcemic paralysis as an initial manifestation of a latent Sjögren's disease. The glandular biopsy was normal, suggesting a mayor participation of an immunological humoral factor in the renal lesion.

  7. Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

    PubMed

    Haberlandt, Edda; Karall, Daniela; Jud, Veronika; Baumgartner, Sara Sigl; Zotter, Sibylle; Rostasy, Kevin; Baumann, Matthias; Scholl-Buergi, Sabine

    2014-04-01

    This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient.

  8. Autoimmune polyglandular syndrome type 3 complicated by mineralocorticoid-responsive hyponatremia of the elderly.

    PubMed

    Yanai, Hidekatsu; Okamoto, Seiko; Kunimatsu, Junwa

    2010-09-15

    We experienced the first case with autoimmune polyglandular syndrome type 3 (anti-thyroid peroxidase antibody-positive hypothyroidism and anti-glutamic acid decarboxylase antibody-positive diabetes) complicated by mineralocorticoid-responsive hyponatremia of the elderly. This case is also a rare slowly progressive insulin-dependent diabetes mellitus (SPIDDM) case, for which the patient has been treated for many years with sulfonylurea or glinide. Our observation also demonstrated that glucose metabolism in autoimmune diabetes such as SPIDDM is influenced by appetite, thyroid function and glucocorticoid effect.

  9. A gene for Usher syndrome type I (USH1A) maps to chromosome 14q

    SciTech Connect

    Kaplan, J.; Gerber, S.; Rozet, J.M.; Delrieu, O.; Briard, M.L.; Dollfus, H.; Frezal, J.; Munnich, A. ); Bonneau, D. ); Ghazi, I. )

    1992-12-01

    Usher syndrome (US) is an autosomal recessive disease characterized by congenital hearing impairment and retinitis pigmentosa. It is the most frequent cause of deaf-blindness in adults and accounts for 3 to 6% of deaf children. Here, the authors report the genetic mapping of a gene for US type I (USH1A), the most severe form of the disease, to the long arm of chromosome 14, by linkage to probe MLJ14 at the D14S13 locus in 10 families of Western France ancestry ([cflx Z] = 4.13 at [cflx [theta

  10. A case of Pfeiffer syndrome type 1 with an A344P mutation in the FGFR2 gene.

    PubMed

    Shotelersuk, V; Srivuthana, S; Ittiwut, C; Theamboonlers, A; Mahatumarat, C; Poovorawan, Y

    2001-06-01

    Pfeiffer syndrome, an autosomal dominant disorder, consists of craniosynostosis, broadening of the thumbs and great toes, and partial soft tissue syndactyly of the hands and feet. Three clinical subtypes have been classified mainly for the purpose of genetic counseling. Mutations in FGFR1 and FGFR2 are known to be associated with the syndrome. However, the correlation between genotype and phenotype is not well defined. Only one patient with Pfeiffer syndrome with no other clinical information has been reported to have had an A344P mutation of the FGFR2. Here we report a Thai male patient with sporadic Pfeiffer syndrome type 1 with impaired intelligence (IQ = 77). Mutation analysis revealed A344P in FGFR2. Identification of the clinical features and molecular defects in more patients is required to better correlate the genotype and phenotype of this complex syndrome.

  11. Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification.

    PubMed

    Robin, N H; Scott, J A; Arnold, J E; Goldstein, J A; Shilling, B B; Marion, R W; Cohen, M M

    1998-01-23

    Pfeiffer syndrome (PS) is an autosomal dominant condition comprising bilateral coronal craniosynostosis, midface hypoplasia with a beaked nasal tip, and broad and medially deviated thumbs and great toes. It is a clinically variable disorder and has been divided into three subtypes [Cohen, 1993: Am J Med Genet 45:300-307]. Type 1 represents the less severe cases, while types 2 and 3 are the more severe cases. These latter types tend to have a higher risk for neurodevelopmental problems and a reduced life expectancy. Here we review the clinical course of seven children with PS type 3. All of these children had severe manifestations of PS; however, development was essentially normal in three, mild delay was noted in two, and moderate delay in one. Favorable outcomes in children with types 2 and 3 PS were also documented by Moore et al. [1995: Cleft Pal-Craniofac J 32:62-70]. These cases illustrate that while children with PS types 2 and 3 have an increased risk for neurodevelopmental difficulties, a favorable outcome can be achieved in some cases with aggressive medical and surgical management. Finally, although such management should be the rule for PS types 2 and 3, it needs to be remembered that normal outcome is not the rule. The prognosis for favorable neurodevelopmental outcome and/or life expectancy remains guarded in most cases.

  12. Oxidative Stress: Dual Pathway Induction in Cardiorenal Syndrome Type 1 Pathogenesis

    PubMed Central

    Virzì, Grazia Maria; Clementi, Anna; de Cal, Massimo; Brocca, Alessandra; Day, Sonya; Pastori, Silvia; Bolin, Chiara; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis. PMID:25821554

  13. FISH approach to determine cat eye syndrome chromosome breakpoints of a patient with cat eye syndrome type II.

    PubMed

    Gentile, M; De Sanctis, S; Cariola, F; Spezzi, T; Di Carlo, A; Tontoli, F; Lista, F; Buonadonna, A L

    2005-01-01

    We report a 19-year-old man with craniofacial dysmorphic features, anorectal malformations, eye colobomas, orthopaedic anomalies, and mild neurodevelopmental delay. Cat eye syndrome (CES) was suspected, and confirmed by cytogenetic analysis which showed the presence of a supernumerary bisatellited chromosome, identified by fluorescence in situ hybridization (FISH) as invdup(22). The marker was further analyzed with six BAC clones located at the 22q11.1 and 22q11.2 regions; this analysis allowed correct assignment at low copy repeat 4 on chromosome 22 (LCR22-4) of the two breakpoints, confirming the presence of a CES chromosome type II. The patient's phenotype is considered in the light of the cytogenetic, and FISH investigations results and other patients reported in literature. Molecular definition of the breakpoints at the LCR22-4 copy confirms the role of different chromosome 22-specific LCRs in CES chromosomes generation, as well as in other chromosome 22 germ line rearrangements. Our report confirms that, unlike other conditions, i.e. the invdup(15) bisatellited dicentric marker, the CES phenotype does not appear to correlate with the size of the marker chromosome. Additional cases are necessary to be able to draw more specific genotype-phenotype correlations and to determine the outcome of patients with CES, especially when this rare condition is diagnosed in prenatal age.

  14. The genetic message of a sudden, unexpected death due to thoracic aortic dissection.

    PubMed

    Ripperger, Tim; Tröger, Hans Dieter; Schmidtke, Jörg

    2009-05-30

    Thoracic aortic aneurysms are associated with sudden, unexpected death due to dissection and/or rupture. In such cases, the latent, preceding state of aortic dilatation has often gone undiagnosed. As a consequence of the sudden unresolved death, medico-legal autopsy requested by a public prosecutor will be the consequence to establish the cause and manner of death. Usually, autopsy records do not include relevant information for differential diagnosis of heritable syndromic and non-syndromic diseases associated with thoracic aortic aneurysms/dissections (TAAD), including e.g. Marfan syndrome, Loeys-Dietz syndrome, and isolated thoracic aortic aneurysms/dissection. However, for at-risk relatives of the deceased, it could be of great benefit to be alerted to the potential heritable aetiology, because early diagnosis of the latent stage of the disease would allow preventive management. Such attempts, including recommendations to seek genetic counselling, are nevertheless rarely made in the context of medico-legal autopsies, in which primarily the legal aspects are considered. We report here on three cases to underline the practical relevance of (i) documentation of relevant information for differential diagnosis of TAAD-associated disorders, (ii) storage of unfixed tissue samples for subsequent molecular genetic testing, and most importantly (iii) the information of relatives at risk. In view of the general ethical principal of nonmaleficience, direct or indirect contact with family members of victims of possible heritable forms of TAAD should be established as a standard of care, also in the medico-legal setting.

  15. [Waardenburg syndrome type I--autosomal dominant hereditary combination of multiple facial anomalies with cochlear deafness (author's transl)].

    PubMed

    Meinecke, P

    1982-03-01

    Waardenburg syndrome Type I is described on the basis of an observation of a family. The characteristic signs including lateral displacement of medial canthi ("telecanthus"), wide bridge of the nose, white forelock and severe cochlear deafness are found in one female patient only; however, her eyes are not of different colour. Five further bearers of characteristic signs in four generations are not so severely affected and show the facial anomalies only. To differentiate this syndrome against Waardenburg syndrome Type II which is complicated by deafness twice as often but occurs without the lateral displacement of the medial canthi, accurate measurement of the distance between the canthi is helpful. Waardenburg syndromes are hereditary according to the autosomal dominant principle with high penetration; intrafamiliarly, too, expressivity can vary greatly. To date treatment has been directed at the signs and symptoms; prognosis is usually favourable. Prevention appears possible through genetic family counseling.

  16. Exploration of differences in types of sleep disturbance and severity of sleep problems between individuals with Cri du Chat syndrome, Down's syndrome, and Jacobsen syndrome: a case control study.

    PubMed

    Maas, Anneke P H M; Didden, Robert; Korzilius, Hubert; Curfs, Leopold M G

    2012-01-01

    The prevalence of sleep problems in individuals with intellectual disability (ID) seems to vary between genetic syndromes associated with ID. Different types of sleep disturbances may indicate underlying causes of sleep problems and these types of sleep disturbances may vary between different genetic syndromes. We examined and compared five types of sleep disturbance as well as severity of sleep problems in individuals with Cri du Chat syndrome (CDC), Down's syndrome (DS), Jacobsen syndrome (JS), and individuals with non-specific ID (NS). We used Simonds and Parraga's Sleep Questionnaire (1982) to assess prevalence of types of sleep disturbance and to explore differences in types of sleep disturbance and severity of sleep problems between the four diagnostic groups. In each group, mean scores for Snoring were significantly higher than those for Sleep apnea and Snoring was the most prevalent type of sleep disturbance in CDC, DS, and JS. The mean score on Complaints related to sleep was remarkably high in the JS group. There were no differences in severity of sleep problems between groups. These findings suggest that snoring is an important underlying cause of sleep problems in individuals with CDS, DS, and JS.

  17. Spontaneous initiation of premature ventricular complexes and arrhythmias in type 2 long QT syndrome.

    PubMed

    Huang, Xiaodong; Kim, Tae Yun; Koren, Gideon; Choi, Bum-Rak; Qu, Zhilin

    2016-12-01

    The occurrence of early afterdepolarizations (EADs) and increased dispersion of repolarization are two known factors for arrhythmogenesis in long QT syndrome. However, increased dispersion of repolarization tends to suppress EADs due to the source-sink effect, and thus how the two competing factors cause initiation of arrhythmias remains incompletely understood. Here we used optical mapping and computer simulation to investigate the mechanisms underlying spontaneous initiation of arrhythmias in type 2 long QT (LQT2) syndrome. In optical mapping experiments of transgenic LQT2 rabbit hearts under isoproterenol, premature ventricular complexes (PVCs) were observed to originate from the steep spatial repolarization gradient (RG) regions and propagated unidirectionally. The same PVC behaviors were demonstrated in computer simulations of tissue models of rabbits. Depending on the heterogeneities, these PVCs could lead to either repetitive focal excitations or reentry without requiring an additional vulnerable substrate. Systematic simulations showed that cellular phase 2 EADs were either suppressed or confined to the long action potential region due to the source-sink effect. Tissue-scale phase 3 EADs and PVCs occurred due to tissue-scale dynamical instabilities caused by RG and enhanced L-type calcium current (ICa,L), occurring under both large and small RG. Presence of cellular EADs was not required but potentiated PVCs when RG was small. We also investigated how other factors affect the dynamical instabilities causing PVCs. Our main conclusion is that tissue-scale dynamical instabilities caused by RG and enhanced ICa,L give rise to both the trigger and the vulnerable substrate simultaneously for spontaneous initiation of arrhythmias in LQT2 syndrome.

  18. EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state.

    PubMed

    Issa, Sarah; Bondurand, Nadege; Faubert, Emmanuelle; Poisson, Sylvain; Lecerf, Laure; Nitschke, Patrick; Deggouj, Naima; Loundon, Natalie; Jonard, Laurence; David, Albert; Sznajer, Yves; Blanchet, Patricia; Marlin, Sandrine; Pingault, Veronique

    2017-02-24

    Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss and pigmentation anomalies. The clinical definition of four WS types is based on additional features due to defects in structures mostly arising from the neural crest, with type I and type II being the most frequent. While type I is tightly associated to PAX3 mutations, WS type II (WS2) remains partly enigmatic with mutations in known genes (MITF, SOX10) accounting for only 30% of the cases. We performed exome sequencing in a WS2 index case and identified a heterozygous missense variation in EDNRB. Interestingly, homozygous (and very rare heterozygous) EDNRB mutations are already described in type IV WS (that is, in association with Hirschsprung disease) and heterozygous mutations in isolated Hirschsprung disease. Screening of a WS2 cohort led to the identification of an overall of 6 heterozygous EDNRB variations. Clinical phenotypes, pedigrees and molecular segregation investigations unraveled a dominant mode of inheritance with incomplete penetrance. In parallel, cellular and functional studies showed that each of the mutations impairs the subcellular localization of the receptor or induces a defective downstream signaling pathway. Based on our results, we now estimate EDNRB mutations to be responsible for 5-6% of WS2. This article is protected by copyright. All rights reserved.

  19. Importance of Laparoscopic Assessment of the Uterine Adnexa in a Mayer-Rokitansky-Kuster-Hauser Syndrome Type II Case.

    PubMed

    Dragusin, Roxana; Tudorache, Ștefania; Surlin, V; Lichiardopol, Corina; Iliescu, D G

    2014-01-01

    In the case reported, diagnosed with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, the presence of normal ovaries proved to be challenging to confirm due to unusual high positioned (ectopic) ovaries. MRKH syndrome is a rare pathological condition characterized by a spectrum of the Mullerian duct abnormalities resulting in congenital aplasia of the uterus and of the upper part (2/3) of the vagina, developed during embryogenesis. At the same time, the mullerian development is interdependent with the Wolffian (mesonephric) duct and this explains the associated renal abnormalities (MRKH type II). Laparoscopic assessment was of great importance in defining the exact anatomic characteristics of MRKH syndrome.

  20. Post-mortem pathologic and genetic studies in "dead in bed syndrome" cases in type 1 diabetes mellitus.

    PubMed

    Tu, Emily; Bagnall, Richard D; Duflou, Johan; Lynch, Matthew; Twigg, Stephen M; Semsarian, Christopher

    2010-03-01

    Dead in bed syndrome is a poorly understood cause of sudden death in young people with type 1 diabetes. The underlying cause remains unknown. One possible explanation may involve prolongation of the QT interval followed by a terminal malignant arrhythmia. Risk factors associated with QT interval prolongation include hypoglycemia and cardiac autonomic neuropathy. We sought to identify myocardial cellular changes and genetic influences that may contribute to the pathogenesis of dead in bed syndrome. Post-mortem reports between 1994 and 2006 from the 2 largest Departments of Forensic Medicine in Australia were reviewed for dead in bed syndrome cases. Post-mortem heart sections were immunohistochemically stained for collagen types I and III and connective tissue growth factor (CTGF). Genomic DNA was prepared from post-mortem samples, and genetic analysis was performed in the SCN5A, G6PC, PHOX2B, and CTGF genes. Twenty-two dead in bed syndrome cases were identified and staining of heart sections for collagen I and III, and CTGF showed no differences between dead in bed syndrome cases and controls. Genetic screening of SCN5A revealed 3 silent polymorphisms A29A, E1061E, and D1819D and 1 protein-changing variant H558R. No genetic variants were found in G6PC, PHOX2B, and CTGF, and dead in bed syndrome cases were not associated with the G-945C CTGF promoter polymorphism. In conclusion, this study is the first to investigate potential pathogenic mechanisms underlying the dead in bed syndrome in type 1 diabetes with the results substantially adding to knowledge of this condition. Understanding the causes and triggers of dead in bed syndrome will be critical in facilitating the identification of patients with type 1 diabetes at highest risk of developing sudden death.

  1. Ultrasonography-guided pulsed radiofrequency of sciatic nerve for the treatment of complex regional pain syndrome Type II

    PubMed Central

    Choi, Yi Hwa; Chang, Dong Jin; Hwang, Woon Suk; Chung, Jin Hwan

    2017-01-01

    Although the major mechanism of complex regional pain syndrome (CRPS) involves dysfunctional central or sympathetic nervous system activation, the peripheral nervous system also contributes significantly to its clinical manifestations. Pulsed radiofrequency (PRF) is a recently developed treatment option for neuropathic pain syndromes. Here, we report a case of CRPS Type II after a femur fracture and sciatic nerve injury, in which the pain was treated successfully with ultrasonography-guided selective sciatic nerve PRF application. PMID:28217060

  2. Clinical and genetic investigation of families with type II Waardenburg syndrome

    PubMed Central

    CHEN, YONG; YANG, FUWEI; ZHENG, HEXIN; ZHOU, JIANDA; ZHU, GANGHUA; HU, PENG; WU, WEIJING

    2016-01-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF), sex-determining region Y-box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease-causing mutation in pedigree 1. However, there are novel disease-causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  3. Delayed diagnosis with autoimmune polyglandular syndrome type 2 causing acute adrenal crisis

    PubMed Central

    Wang, Xiaojing; Ping, Fan; Qi, Cuijuan; Xiao, Xinhua

    2016-01-01

    Abstract Background: Autoimmune polyglandular syndrome type 2 (APS-2), also known as Schmidt's syndrome, is an uncommon disorder characterized by the coexistence of Addison's disease with thyroid autoimmune disease and/or type 1 diabetes mellitus. Addison's disease as the obligatory component is potentially life-threatening. Unfortunately, the delayed diagnosis of Addison's disease is common owing to its rarity and the nonspecific clinical manifestation. Methods: Here we reported a case of 38-year-old female patient who presented with 2 years’ history of Hashimoto's thyroiditis and received levothyroxine replacement. One year later, skin hyperpigmentation, fatigue, loss of appetite, and muscle soreness occurred. She was advised to increase the dose of levothyroxine, but the symptoms were not relieved. After 4 months, the patient accompanied with dizziness, nausea, nonbloody vomiting, and fever. However, she was diagnosed with acute gastroenteritis and fell into shock and ventricular fibrillation subsequently. Further evaluation in our hospital revealed elevated adrenocorticotrophic hormone and low morning serum cortisol, associated with hyponatremia and atrophic adrenal gland. Hypergonadotropic hypogonadism and Hashimoto's thyroiditis were also demonstrated. Results: After the supplementation with hydrocortisone and fludrocortisone was initiated, the physical discomforts were alleviated and plasma electrolytes were back to normal. Conclusion: The uncommon case involving 3 endocrine organs reinforced the significance of a timely diagnosis and appropriate treatment of APS-2, and physicians needed to sharpen their awareness of the potentially life-threatening disease. PMID:27759634

  4. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report

    PubMed Central

    Hu, Soo-young; Choi, Jin-gyu

    2015-01-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia. PMID:27169091

  5. Complex Regional Pain Syndrome Type II Secondary to Endovascular Aneurysm Repair

    PubMed Central

    Chen, Hamilton; Tafazoli, Sharwin

    2015-01-01

    Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by severe pain and vasomotor and pseudomotor changes. Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms is a recent advance in vascular surgery that has allowed repair of AAA while offering reduced intensive care unit and hospital lengths of stay, reduced blood loss, fewer major complications, and more rapid recovery. Pseudoaneurysms are a rare complication of an EVAR procedure that may result in a wide range of complications. The present report examines CRPS type II as a novel consequence of pseudoaneurysm formation from brachial artery access in the EVAR procedure. To our knowledge, this is the first reported case of CRPS type II presentation as sequelae of an EVAR procedure. PMID:25650247

  6. Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome

    PubMed Central

    Sun, Lianhua; Li, Xiaohua; Shi, Jun; Pang, Xiuhong; Hu, Yechen; Wang, Xiaowen; Wu, Hao; Yang, Tao

    2016-01-01

    Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10−4). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations. PMID:27759048

  7. Marked, transient, emotion-triggered QT accentuation in an adolescent female with type 1 long QT syndrome.

    PubMed

    Anderson, Heather N; Medford, Beth A; Ackerman, Michael J

    2015-02-01

    Type 1 long QT syndrome is the most common long QT syndrome genetic subtype. Exercise and emotional stress can precipitate sudden cardiac events in patients with type 1 long QT syndrome; however, the precise mechanism remains elusive. We report the case of a teenage girl with type 1 long QT syndrome secondary to a rare frameshift mutation (p. L191fs+90X) in the KCNQ1-encoded Kv7.1 potassium channel. During emotional distress, her continuous QTc recordings precipitously increased, peaking within minutes to 669 ms and then returning to baseline (520 ms) as she calmed without concomitant increase in heart rate. This is the first described case documenting transient, marked accentuation of the QTc interval in a long QT syndrome patient during emotional distress. Such events may be triggered by transient accentuation of the intrinsic perturbation in cardiac repolarisation and increase the risk of degeneration to a ventricular arrhythmia. This case illustrates the need improved understanding of the complex interaction between emotion and cardiac stability in patients with long QT syndrome.

  8. Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

    PubMed

    Saito, Isao

    2012-01-01

    Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

  9. Pre- and Postoperative Imaging of the Aortic Root

    PubMed Central

    Chan, Frandics P.; Mitchell, R. Scott; Miller, D. Craig; Fleischmann, Dominik

    2016-01-01

    Three-dimensional datasets acquired using computed tomography and magnetic resonance imaging are ideally suited for characterization of the aortic root. These modalities offer different advantages and limitations, which must be weighed according to the clinical context. This article provides an overview of current aortic root imaging, highlighting normal anatomy, pathologic conditions, imaging techniques, measurement thresholds, relevant surgical procedures, postoperative complications and potential imaging pitfalls. Patients with a range of clinical conditions are predisposed to aortic root disease, including Marfan syndrome, bicuspid aortic valve, vascular Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Various surgical techniques may be used to repair the aortic root, including placement of a composite valve graft, such as the Bentall and Cabrol procedures; placement of an aortic root graft with preservation of the native valve, such as the Yacoub and David techniques; and implantation of a biologic graft, such as a homograft, autograft, or xenograft. Potential imaging pitfalls in the postoperative period include mimickers of pathologic processes such as felt pledgets, graft folds, and nonabsorbable hemostatic agents. Postoperative complications that may be encountered include pseudoaneurysms, infection, and dehiscence. Radiologists should be familiar with normal aortic root anatomy, surgical procedures, and postoperative complications, to accurately interpret pre- and postoperative imaging performed for evaluation of the aortic root. Online supplemental material is available for this article. ©RSNA, 2015 PMID:26761529

  10. A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms.

    PubMed

    Courtois, Audrey; Coppieters, Wouter; Bours, Vincent; Defraigne, Jean-Olivier; Colige, Alain; Sakalihasan, Natzi

    2017-04-01

    Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis. Exome-sequencing revealed a new frameshift heterozygous c.455delC (p.Pro152Hisfs*34) mutation in the SMAD3 gene. This deletion is located in the exon 3 coding for the linker region of the protein and causes a premature stop codon at positions 556-558 in the exon 4. The same mutation was found in the proband's mother and sister who had open surgery for abdominal aortic aneurysm and in one of his children who was 5 year-old and did not present aneurysm yet.

  11. Twins with progressive thoracic aortic aneurysm, recurrent dissection and ACTA2 mutation.

    PubMed

    Ware, Stephanie M; Shikany, Amy; Landis, Benjamin J; James, Jeanne F; Hinton, Robert B

    2014-10-01

    Thoracic aortic aneurysm (TAA) is a genetically mediated disease with variable age of onset. In the pediatric age range, nonsyndromic TAA frequently has a milder course than syndromic forms of TAA, such as Marfan syndrome or Loeys-Dietz syndrome. Herein, we describe 17-year-old identical twin brothers with severe progressive TAA due to a novel de novo ACTA2 mutation. Interestingly, both boys were diagnosed at age 11 with congenital mydriasis, a recently recognized manifestation of some ACTA2 mutations due to smooth muscle dysfunction. One of the brothers presented with acute-onset lower back pain that was identified as dissection of an abdominal aortic aneurysm. Imaging of the chest at this time showed severe fusiform TAA. Cardiac imaging in his twin showed similar TAA, but no abdominal aortic aneurysm. Both brothers underwent valve-sparing aortic root replacement, but have had progressive aortic disease with recurrent dissection requiring multiple surgeries. This case emphasizes the importance of identifying physical stigmata of smooth muscle dysfunction, such as mydriasis, as potential markers for associated aortopathy and vascular diseases.

  12. Alport syndrome

    MedlinePlus

    ... Autosomal dominant Alport syndrome (ADAS) -- This is the rarest type. Males and females have equally severe disease. Symptoms KIDNEYS With all types of Alport syndrome the kidneys are affected. The tiny blood vessels in the glomeruli of the kidneys are ...

  13. Pathological and biochemical studies of mucopolysaccharidosis type IIIB (Sanfilippo syndrome type B) in juvenile emus (Dromaius novaehollandiae).

    PubMed

    Palmieri, C; Giger, U; Wang, P; Pizarro, M; Shivaprasad, H L

    2015-01-01

    Mucopolysaccharidosis (MPS) type IIIB was diagnosed in 14 juvenile emus (Dromaius novaehollandiae), ages 3 weeks to 6 months, based on pathological and biochemical analyses. The animals had a history of neurological signs or sudden death; one of the birds with neurological signs and 3 others experienced acute hemoabdomen. Histopathologically, neuronal swelling and vacuolation in the cerebrum, cerebellum, brainstem, and spinal cord (80%-92%); retina (100%); autonomic ganglia of the intestine (71%); gizzard (50%); adrenal gland (27%); and ear (50%) were noted in affected but not healthy emus. Cytoplasmic vacuoles were also observed in the pancreas, liver, intestine, adrenal glands, and kidneys. The intracytoplasmic inclusions were periodic acid-Schiff and Luxol Fast Blue positive, consistent with a storage disease. Foamy macrophages infiltrated the liver, intestine, tunica media of the aorta, and spleen. By transmission electron microscopy, typical lamellated cytoplasmic bodies were detected in neurons of the brain and retina, while electron-dense bodies consistent with glycosaminoglycan inclusions were observed in hepatocytes and/or hepatic macrophages. The livers of the 2 affected emus studied contained large amounts of heparan sulfate, which is suggestive of MPS type III. Compared with normal controls, hepatic and serum α-N-acetylglucosaminidase activity was very low (<8% of control), while other enzyme activities were normal to increased in the 2 affected emus studied. Moreover, affected emus were homozygous for a 2-bp deletion in the NAGLU gene. This study characterizes the pathology of MPS type IIIB in emus, which is one of the rare inborn errors in birds, showing the homology of this condition to Sanfilippo syndrome in humans.

  14. Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome previously diagnosed as Seckel syndrome: report of a novel mutation of the PCNT gene.

    PubMed

    Piane, Maria; Della Monica, Matteo; Piatelli, Gianluca; Lulli, Patrizia; Lonardo, Fortunato; Chessa, Luciana; Scarano, Gioacchino

    2009-11-01

    We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested.

  15. [Pena-Shokeir syndrome type I--combination of polyhydramnios and pulmonary hypoplasia in fetal akinesia].

    PubMed

    Deli, Tamás; Kovács, Tamás

    2010-06-13

    We present the case of an 18-year-old woman with her second pregnancy, whose first pregnancy was complicated by polyhydramnios. At week 30, the dysmorph fetus died in utero and was delivered via cesarean section due to placental abruption, but the exact diagnosis was not recognized at that time. During the patient's second pregnancy, increasing polyhydramnios was detected from the 19th gestational week. Ultrasound signs of fetal malformation also appeared later: abnormal position of limbs, narrow chest, oedema around the skull, and absence of stomach content. At week 34, decompression amniocentesis became necessary. Chromosome analysis was also carried out and a normal karyotype was obtained. At 39th gestational week, amnioscopy proved meconium staining of the amniotic fluid, thus labour was induced. Following amniotomy, sustained fetal bradycardia commenced and an emergency caesarean section was performed. Despite complex resuscitation, the 3000 gram male newborn died 2.5 hours after delivery, due to respiratory failure. Autopsy and histopathologic examination revealed a large, oedematous head, micrognathia, macroglossia, laryngeal oedema, narrow chest with pulmonary hypoplasia, gracile limbs with muscle atrophy, gracile and bent fingers, and a short umbilical cord. Based on the medical history, the course of the disease and the phenotype of the newborn, Pena-Shokeir syndrome type I was diagnosed. In the second part of the article, we review the etiology, pathogenesis, prenatal diagnosis and differential diagnosis of this syndrome, as well as some aspects of genetic counseling in such cases. To our knowledge, this is the first reported case of Pena-Shokeir syndrome in Hungary.

  16. Novel association of neurofibromatosis type 1-causing mutations in families with neurofibromatosis-Noonan syndrome.

    PubMed

    Ekvall, Sara; Sjörs, Kerstin; Jonzon, Anders; Vihinen, Mauno; Annerén, Göran; Bondeson, Marie-Louise

    2014-03-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a rare condition with clinical features of both neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). All three syndromes belong to the RASopathies, which are caused by dysregulation of the RAS-MAPK pathway. The major gene involved in NFNS is NF1, but co-occurring NF1 and PTPN11 mutations in NFNS have been reported. Knowledge about possible involvement of additional RASopathy-associated genes in NFNS is, however, very limited. We present a comprehensive clinical and molecular analysis of eight affected individuals from three unrelated families displaying features of NF1 and NFNS. The genetic etiology of the clinical phenotypes was investigated by mutation analysis, including NF1, PTPN11, SOS1, KRAS, NRAS, BRAF, RAF1, SHOC2, SPRED1, MAP2K1, MAP2K2, and CBL. All three families harbored a heterozygous NF1 variant, where the first family had a missense variant, c.5425C>T;p.R1809C, the second family a recurrent 4bp-deletion, c.6789_6792delTTAC;p.Y2264Tfs*6, and the third family a splice-site variant, c.2991-1G>A, resulting in skipping of exon 18 and an in-frame deletion of 41 amino acids. These NF1 variants have all previously been reported in NF1 patients. Surprisingly, both c.6789_6792delTTAC and c.2991-1G>A are frequently associated with NF1, but association to NFNS has, to our knowledge, not previously been reported. Our results support the notion that NFNS represents a variant of NF1, genetically distinct from NS, and is caused by mutations in NF1, some of which also cause classical NF1. Due to phenotypic overlap between NFNS and NS, we propose screening for NF1 mutations in NS patients, preferentially when café-au-lait spots are present.

  17. Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis

    PubMed Central

    Ben-Rebeh, Imen; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

    2016-01-01

    Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. Methods In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Results Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. Conclusions We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient’s early childhood is of utmost importance, allowing better educational and therapeutic management. PMID:27440999

  18. Type II diabetes of early onset: a distinct clinical and genetic syndrome?

    PubMed Central

    O'Rahilly, S; Spivey, R S; Holman, R R; Nugent, Z; Clark, A; Turner, R C

    1987-01-01

    The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID:3107658

  19. Vascular Ehlers-Danlos syndrome mutations in type III collagen differently stall the triple helical folding.

    PubMed

    Mizuno, Kazunori; Boudko, Sergei; Engel, Jürgen; Bächinger, Hans Peter

    2013-06-28

    Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at a low temperature. At 33 °C, the natural collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at Gly-910 and at the C terminus at Gly-1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue.

  20. Impaired Empathic Abilities among Patients with Complex Regional Pain Syndrome (Type I)

    PubMed Central

    Sohn, Hong-Suk; Lee, Do-Hyeong; Lee, Kyung-Jun; Noh, Eun Chung; Choi, Soo-Hee; Jang, Joon Hwan; Kim, Yong Chul

    2016-01-01

    Objective The aims of this study were to evaluate differences in empathic abilities between patients with complex regional pain syndrome (CRPS) Type I and healthy control subjects (HCs) and to assess correlations between empathic abilities and multidimensional aspects of pain. Methods Empathic ability was measured in 32 patients with CRPS Type I and in 36 HCs using the Interpersonal Reactivity Index (IRI). A comprehensive assessment of pain was conducted in the patient group using the West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Psychiatric symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI and BAI), and quality of life was evaluated using the WHO Quality of Life (WHOQOL-BREF) questionnaire. Results Patients with CRPS showed impaired cognitive and emotional empathic abilities compared with HCs. Significantly lower levels of perspective taking and empathic concern and higher levels of personal distress on the IRI were exhibited by the patient group. Perspective taking and personal distress were associated with affective distress and poor quality of life in social contexts (BDI, BAI, and WHOQOL). However, empathic concern was positively correlated with pain severity and social support from others (WHYMPI). Conclusion A tendency toward self-oriented distress in social cognition was exhibited among patients with CRPS Type I. Impaired empathic ability was shown to have potentially negative effects on subjective emotional outcomes and social performance in the lives of patients. Interventions to improve emotional awareness and theory of mind would be beneficial for enhancing social functioning in patients with CRPS Type I. PMID:26766944

  1. The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes.

    PubMed

    Hur, Junguk; Dauch, Jacqueline R; Hinder, Lucy M; Hayes, John M; Backus, Carey; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

    2015-09-01

    To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.

  2. [Brain abscess caused by Haemophilus influenzae type E in a pediatric patient suffering from Apert syndrome].

    PubMed

    Isasmendi, Adela M; Pinheiro, José L; Escudé, Natalia García; Efrón, Adriana M; Moscoloni, María A; Hernández, Claudia M

    2014-01-01

    We report a case of a brain abscess caused by Haemophilus influenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fluid fistula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identified as Haemophilus influenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition.

  3. [Mutation screening of MITF gene in patients with Waardenburg syndrome type 2].

    PubMed

    Chen, Jing; Yang, Shu-Zhi; Liu, Jun; Han, Bing; Wang, Guo-Jian; Zhang, Xin; Kang, Dong-Yang; Dai, Pu; Young, Wie-Yen; Yuan, Hui-Jun

    2008-04-01

    Warrgenburg syndrome type 2 (WS2) is the most common autosomal dominantly-inherited syndrome with hearing loss. MITF (microphthalmia associated transcription factor)is a basic-helix-loop-helix-luecine zipper (bHLHZip) factor which regulates expression of tyrosinase, and is involved in melanocyte differentiation. Mutations in MITF associated with WS2 have been identified in some but not all affected families. Here, we report a three-generation Chinese family with a point mutation in the MITF gene causing WS2. The proband exhibits congenital severe sensorineural hearing loss, heterochromia iridis and facial freckles. One of family members manifests sensorineural deafness, and the other patients show premature greying or/and freckles. This mutation, heterozygous deletion c.639delA, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking normal interaction with its target DNA motif. This mutation is a novel mutation and the third case identified in exon 7 of MITF in WS2. Though there is only one base pair distance between this novel mutation and the other two documented cases and similar amino acids change, significant difference is seen in clinical phenotype, which suggests genetic background may play an important role.

  4. Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

    PubMed Central

    de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

    2016-01-01

    Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

  5. The use of cone beam computed tomography for the assessment of trichorhinophalangeal syndrome, type I – a case report

    PubMed Central

    Ghoneima, Ahmed; Sachdeva, Kanwar; Hartsfield, James; Weaver, David; Kula, Katherine

    2016-01-01

    Trichorhinophalangeal syndrome type I is a rare autosomal dominant disorder characterized by cone-shaped epiphysis, sparse fine hair, pear-shaped nose and variable growth retardation. The typical craniofacial features include thin upper lip, elongated philtrum, large outstanding ears, shortened posterior facial height associated with short mandibular ramus and reduced and superiorly deflected posterior cranial base. This report describes a 17-year-old male patient with trichorhinophalangeal syndrome type I and a detailed description of the craniofacial radiographic findings, including the use of cone beam computed tomography images for determination of the airway and temporomandibular joint discrepancies. PMID:23524547

  6. Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).

    PubMed

    Ishikiriyama, S; Tonoki, H; Shibuya, Y; Chin, S; Harada, N; Abe, K; Niikawa, N

    1989-08-01

    We report on a child with Waardenburg syndrome type I and a paracentric inversion of chromosome 2. This 20 month-old boy has dystopia canthorum, sensorineural deafness, heterochromia iridis, partially albinotic ocular fundi, and partial leukodermia. He does not have mental retardation or any skeletal abnormalities. Family history was unremarkable. Cytogenetic studies demonstrated that the patient has a paracentric inversion (2)(q35q37.3); his parents have normal chromosomes. These findings suggest that the locus of the gene for Waardenburg syndrome type I may be at 2q35 or 2q37.3.

  7. Anti glutamate-decarboxylase antibodies: a liaison between localisation related epilepsy, stiff-person syndrome and type-1 diabetes mellitus.

    PubMed

    Szűcs, Anna; Barcs, Gábor; Winkler, Gábor; Soós, Zsuzsanna; Folyovich, András; Kelemen, Anna; Várallyay, Péter; Kamondi, Anita

    2014-07-30

    We present two patients with partial epilepsy, type-1 diabetes and stiff person syndrome associated with high serum auto-antibody levels to glutamate-decarboxylase (anti-GAD). Both patients were or have suffered from additional autoimmune conditions. The presence of stiff person syndrome and elevated anti-GAD levels have to make clinicians look for additional autoimmune conditions including type-1 diabetes. On the other hand, the co-morbidity of partial epilepsy with autoimmune conditions in patients with elevated serum anti-GAD suggests an autoimmune mechanism of partial epilepsy in these cases.

  8. 11β-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.

    PubMed

    Pereira, C D; Azevedo, I; Monteiro, R; Martins, M J

    2012-10-01

    Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11β-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11β-HSD1) or inactivate cortisol to cortisone (11β-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11β-HSD1 as a possible pharmacological target and into the role of dietary habits on the

  9. High Incidence of BSCL2 Intragenic Recombinational Mutation in Peruvian Type 2 Berardinelli–Seip Syndrome

    PubMed Central

    Purizaca-Rosillo, Nelson; Mori, Takayasu; Benites-Cóndor, Yamali; Hisama, Fuki M.; Martin, George M.; Oshima, Junko

    2017-01-01

    Congenital generalized lipodystrophy (CGL) is a genetically heterogeneous group of disorders characterized by the absence of functional adipose tissue. We identified two pedigrees with CGL in the community of the Mestizo tribe in the northern region of Peru. Five cases, ranging from 15 months to 7 years of age, presented with generalized lipodystrophy, muscular prominence, mild intellectual disability, and a striking aged appearance. Sequencing of the BSCL2 gene, known to be mutated in type 2 CGL (CGL2; Berardinelli–Seip syndrome), revealed a homozygous deletion of exon 3 in all five patients examined, suggesting the presence of a founder mutation. This intragenic deletion appeared to be mediated by recombination between Alu sequences in introns 2 and 3. CGL2 in this population is likely underdiagnosed and undertreated because of its geographical, socio-economic, and cultural isolation. PMID:27868354

  10. Biochemical characterization of variants of the Ehlers-Danlos syndrome type VI.

    PubMed

    Ihme, A; Risteli, L; Krieg, T; Risteli, J; Feldmann, U; Kruse, K; Müller, P K

    1983-08-01

    Three variants of the Ehlers-Danlos syndrome type VI are described: a severe form with skeletal, dermal and ocular manifestations associated with a lack of hydroxylysine in skin and little lysyl hydroxylase activity in cultured fibroblasts; a similarly affected form with a nearly normal hydroxylsine content in skin, but with only little enzyme activity in cultured fibroblasts; and a predominantly ocular form with no biochemical abnormality in skin or cultured skin fibroblasts. The activities of prolyl 4-hydroxylase and the two hydroxylysyl glycosyltransferases were normal in all cases, and the failure to find lysyl hydroxylase activity was not due to altered solubility characteristics of the enzyme or to the presence of an enzyme inhibitor. The collagen produced in cell culture, however, was hydroxylated to a markedly higher extent than that found in skin. In both the mutant and control cells hydroxylation of lysyl residues was less sensitive to ascorbate deficiency than that of prolyl residues.

  11. Cardiac arrest secondary to type 2 Kounis syndrome resulting from urticaria and angioedema.

    PubMed

    Connor, Suzy; Child, Nick; Burdon-Jones, David; Connor, Andrew

    2010-07-01

    A 43-year-old man with no cardiac history presented with chest pain followed by cardiac arrest. He was successfully defibrillated and underwent primary percutaneous coronary angioplasty to a culprit coronary artery lesion. He later re-presented with a diffuse urticarial rash and lip swelling, reporting that these symptoms had been present for 4 weeks before his cardiac arrest and voicing concern that a further cardiac arrest may be imminent. A diagnosis of post-viral or idiopathic autoimmune urticaria and angioedema was made. Given the absence of cardiac symptoms before the development of the rash, it was hypothesised that coronary artery spasm precipitated by histamine release due to his dermatological condition contributed to his myocardial infarction and cardiac arrest. The final diagnosis was therefore cardiac arrest secondary to type II Kounis syndrome, resulting from idiopathic autoimmune or post-viral urticaria and angioedema.

  12. Glomerular Glucocorticoid Receptors Expression and Clinicopathological Types of Childhood Nephrotic Syndrome.

    PubMed

    Gamal, Yasser; Badawy, Ahlam; Swelam, Salwa; Tawfeek, Mostafa S K; Gad, Eman Fathalla

    2017-02-01

    Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS). However, not all children respond to steroid therapy. We assessed glomerular glucocorticoid receptor expression in fifty-one children with INS and its relation to response to steroid therapy and to histopathological type. Clinical, laboratory and glomerular expression of glucocorticoid receptors were compared between groups with different steroid response. Glomerular glucocorticoid expression was slightly higher in controls than in minimal change early responders, which in turn was significantly higher than in minimal change late responders. There was significantly lower glomerular glucocorticoid receptor expression in steroid-resistance compared to early responders, late responders and controls. Glomerular glucocorticoid expression was significantly higher in all minimal change disease (MCD) compared to focal segmental glomerulosclerosis. In INS, response to glucocorticoid is dependent on glomerular expression of receptors and peripheral expression. Evaluation of glomerular glucocorticoid receptor expression at time of diagnosis of NS can predict response to steroid therapy.

  13. Polyglandular autoimmune syndrome type I – a novel AIRE mutation in a North American patient

    PubMed Central

    Huibregtse, Kelly Egan; Wolfgram, Peter; Winer, Karen K.; Connor, Ellen L.

    2015-01-01

    Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autoimmune disease that results from autosomal recessive mutations of the human autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North American girl of primarily Norwegian descent with a novel AIRE gene mutation causing APS-1. In addition to the classic triad of chronic candidiasis, hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive. Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13 mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been previously reported. PMID:24945421

  14. Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge–Weber Syndrome

    PubMed Central

    Stafstrom, Carl E.; Staedtke, Verena; Comi, Anne M.

    2017-01-01

    Neurocutaneous disorders are multisystem diseases affecting skin, brain, and other organs. Epilepsy is very common in the neurocutaneous disorders, affecting up to 90% of patients with tuberous sclerosis complex (TSC) and Sturge–Weber syndrome (SWS), for example. The mechanisms underlying the increased predisposition to brain hyperexcitability differ between disorders, yet some molecular pathways overlap. For instance, the mechanistic target of rapamycin (mTOR) signaling cascade plays a central role in seizures and epileptogenesis in numerous acquired and genetic disorders, including several neurocutaneous disorders. Potential routes for target-specific treatments are emerging as the genetic and molecular pathways involved in neurocutaneous disorders become increasingly understood. This review explores the clinical features and mechanisms of epilepsy in three common neurocutaneous disorders—TSC, neurofibromatosis type 1, and SWS. PMID:28367137

  15. Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I.

    PubMed Central

    Rosatelli, M C; Meloni, A; Faa, V; Saba, L; Crisponi, G; Clemente, M G; Meloni, G; Piga, M T; Cao, A

    1997-01-01

    This study reports the molecular characterisation of the bilirubin UDP-glucuronosyl-transferase gene (UGT1) in a group of patients of Sardinian descent with Crigler-Najjar syndrome type I and their relatives. Sequence analysis of both UGT1A exon 1 and common exons 2-5 was performed in all patients, leading to the detection of AF170 and a novel mutation (470insT), both residing in UGT1A exon 1. All but two heterozygotes for the AF170 mutation showed normal serum bilirubin levels. These two subjects were also heterozygous for the sequence variation A(TA)7TAA in the promoter region of the UGT1A gene. Images PMID:9039987

  16. Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and what's old.

    PubMed

    Falchetti, Alberto

    2017-01-01

    Despite its identification in 1997, the functions of the MEN1 gene-the main gene underlying multiple endocrine neoplasia type 1 syndrome-are not yet fully understood. In addition, unlike the RET-MEN2 causative gene-no hot-spot mutational areas or genotype-phenotype correlations have been identified. More than 1,300 MEN1 gene mutations have been reported and are mostly "private" (family specific). Even when mutations are shared at an intra- or inter-familial level, the spectrum of clinical presentation is highly variable, even in identical twins. Despite these inherent limitations for genetic counseling, identifying MEN1 mutations in individual carriers offers them the opportunity to have lifelong clinical surveillance schemes aimed at revealing MEN1-associated tumors and lesions, dictates the timing and scope of surgical procedures, and facilitates specific mutation analysis of relatives to define presymptomatic carriers.

  17. Natural History of Sanfilippo Syndrome Type C in Boyacá, Colombia.

    PubMed

    Velasco, Harvy Mauricio; Sanchez, Yasmin; Martin, Angela Milena; Umaña, Luis A

    2017-02-01

    Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT. The authors report an unusually high incidence of the disease in this population. The clinical features are similar to previously described patients, although some differences in the degree of severity and end-stage of the disease are seen in this specific group. The authors consider that the high degree of endogamy in this specific population could underlie modifying factors for the severity of presentation in these patients. Future studies might provide more information on the functional effect of this novel mutation, which could define this group as a genetic isolate.

  18. Cardiorenal Syndrome Type 1: Renal Dysfunction in Acute Decompensated Heart Failure

    PubMed Central

    Prins, Kurt W.; Thenappan, Thenappan; Markowitz, Jeremy S.; Pritzker, Marc R.

    2016-01-01

    Objective To present a review of cardiorenal syndrome type 1 (CRS1). Methods Review of the literature. Results Acute kidney injury occurs in approximately one-third of patients with acute decompensated heart failure (ADHF) and the resultant condition was named CRS1. A growing body of literature shows CRS1 patients are at high risk for poor outcomes, and thus there is an urgent need to understand the pathophysiology and subsequently develop effective treatments. In this review we discuss prevalence, proposed pathophysiology including hemodynamic and nonhemodynamic factors, prognosticating variables, data for different treatment strategies, and ongoing clinical trials and highlight questions and problems physicians will face moving forward with this common and challenging condition. Conclusion Further research is needed to understand the pathophysiology of this complex clinical entity and to develop effective treatments. PMID:27158218

  19. Concise Review: Methods and Cell Types Used to Generate Down Syndrome Induced Pluripotent Stem Cells

    PubMed Central

    Hibaoui, Youssef; Feki, Anis

    2015-01-01

    Down syndrome (DS, trisomy 21), is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Several models have been used to investigate the mechanisms by which the extra copy of chromosome 21 leads to the DS phenotype. In the last five years, several laboratories have been successful in reprogramming patient cells carrying the trisomy 21 anomaly into induced pluripotent stem cells, i.e., T21-iPSCs. In this review, we summarize the different T21-iPSCs that have been generated with a particular interest in the technical procedures and the somatic cell types used for the reprogramming. PMID:26239351

  20. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED): A "Rare" Manifestation in a "Rare" Disease.

    PubMed

    Fierabracci, Alessandra

    2016-07-12

    Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome.

  1. Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.

    PubMed

    Cortés-González, Vianney; Zenteno, Juan Carlos; Guzmán-Sánchez, Martín; Giordano-Herrera, Verónica; Guadarrama-Vallejo, Dalia; Ruíz-Quintero, Narlly; Villanueva-Mendoza, Cristina

    2016-12-01

    Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc.

  2. Sanfilippo syndrome type B, a lysosomal storage disease, is also a tauopathy.

    PubMed

    Ohmi, Kazuhiro; Kudo, Lili C; Ryazantsev, Sergey; Zhao, Hui-Zhi; Karsten, Stanislav L; Neufeld, Elizabeth F

    2009-05-19

    Sanfilippo syndrome type B (mucopolysaccharidosis III B, MPS III B) is an autosomal recessive, neurodegenerative disease of children, characterized by profound mental retardation and dementia. The primary cause is mutation in the NAGLU gene, resulting in deficiency of alpha-N-acetylglucosaminidase and lysosomal accumulation of heparan sulfate. In the mouse model of MPS III B, neurons and microglia display the characteristic vacuolation of lysosomal storage of undegraded substrate, but neurons in the medial entorhinal cortex (MEC) display accumulation of several additional substances. We used whole genome microarray analysis to examine differential gene expression in MEC neurons isolated by laser capture microdissection from Naglu(-/-) and Naglu(+/-) mice. Neurons from the lateral entorhinal cortex (LEC) were used as tissue controls. The highest increase in gene expression (6- to 7-fold between mutant and control) in MEC and LEC neurons was that of Lyzs, which encodes lysozyme, but accumulation of lysozyme protein was seen in MEC neurons only. Because of a report that lysozyme induced the formation of hyperphosphorylated tau (P-tau) in cultured neurons, we searched for P-tau by immunohistochemistry. P-tau was found in MEC of Naglu(-/-) mice, in the same neurons as lysozyme. In older mutant mice, it was also seen in the dentate gyrus, an area important for memory. Electron microscopy of dentate gyrus neurons showed cytoplasmic inclusions of paired helical filaments, P-tau aggregates characteristic of tauopathies-a group of age-related dementias that include Alzheimer disease. Our findings indicate that the Sanfilippo syndrome type B should also be considered a tauopathy.

  3. Delineation and diagnostic criteria of Oral-Facial-Digital Syndrome type VI.

    PubMed

    Poretti, Andrea; Vitiello, Giuseppina; Hennekam, Raoul C M; Arrigoni, Filippo; Bertini, Enrico; Borgatti, Renato; Brancati, Francesco; D'Arrigo, Stefano; Faravelli, Francesca; Giordano, Lucio; Huisman, Thierry A G M; Iannicelli, Miriam; Kluger, Gerhard; Kyllerman, Marten; Landgren, Magnus; Lees, Melissa M; Pinelli, Lorenzo; Romaniello, Romina; Scheer, Ianina; Schwarz, Christoph E; Spiegel, Ronen; Tibussek, Daniel; Valente, Enza Maria; Boltshauser, Eugen

    2012-01-11

    Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly

  4. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment

    PubMed Central

    2010-01-01

    Overweight and obesity in youth is a worldwide public health problem. Overweight and obesity in childhood and adolescents have a substantial effect upon many systems, resulting in clinical conditions such as metabolic syndrome, early atherosclerosis, dyslipidemia, hypertension and type 2 diabetes (T2D). Obesity and the type of body fat distribution are still the core aspects of insulin resistance and seem to be the physiopathologic links common to metabolic syndrome, cardiovascular disease and T2D. The earlier the appearance of the clustering of risk factors and the higher the time of exposure, the greater will be the chance of developing coronary disease with a more severe endpoint. The age when the event may occur seems to be related to the presence and aggregation of risk factors throughout life. The treatment in this age-group is non pharmacological and aims at promoting changes in lifestyle. However, pharmacological treatments are indicated in special situations. The major goals in dietary treatments are not only limited to weight loss, but also to an improvement in the quality of life. Modification of risk factors associated to comorbidities, personal satisfaction of the child or adolescent and trying to establish healthy life habits from an early age are also important. There is a continuous debate on the best possible exercise to do, for children or adolescents, in order to lose weight. The prescription of physical activity to children and adolescents requires extensive integrated work among multidisciplinary teams, patients and their families, in order to reach therapeutic success. The most important conclusion drawn from this symposium was that if the growing prevalence of overweight and obesity continues at this pace, the result will be a population of children and adolescents with metabolic syndrome. This would lead to high mortality rates in young adults, changing the current increasing trend of worldwide longevity. Government actions and a better

  5. Concurrent vaccination of pigs with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) protects against type 1 PRRSV but not against type 2 PRRSV on dually challenged pigs.

    PubMed

    Park, Changhoon; Choi, Kyuhyung; Jeong, Jiwoon; Kang, Ikjae-; Park, Su-Jin; Chae, Chanhee

    2015-12-01

    The objective of the present study was to evaluate the effect of concurrent vaccination of pigs with both type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against heterologous dual challenge of both genotypes and compare with single vaccination of pigs against heterologous single challenge of both genotypes. Pigs were administered both type 1 and type 2 PRRSV vaccine concurrently into separate anatomical sites at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Neutralizing antibodies (NA) were not detected in any pigs in any group (NA titer <2 log2) throughout the experiment. In addition, concurrent vaccination of pigs with two PRRSV genotypes had significantly lower numbers of type 1 and type 2 PRRSV-specific interferon-γ secreting cells (IFN-γ-SC) compared to vaccination of pigs with type 1 or type 2 PRRSV only. Despite the decreased induction of type 1 PRRSV-specific IFN-γ-SC, concurrent vaccination is still able to reduce type 1 PRRSV viremia whereas the decreased induction of type 2 PRRSV-specific IFN-γ-SC by concurrent vaccination correlates with lack of reduction of type 2 PRRSV viremia after dual challenge. The results of this study demonstrated that concurrent vaccination of pigs with two PRRSV genotypes is able to reduce the levels of type 1 PRRSV viremia and lung lesions but not able to reduce the levels of type 2 PRRSV viremia and lung lesions.

  6. Dual compression is not an uncommon type of iliac vein compression syndrome.

    PubMed

    Shi, Wan-Yin; Gu, Jian-Ping; Liu, Chang-Jian; Lou, Wen-Sheng; He, Xu

    2017-03-13

    Typical iliac vein compression syndrome (IVCS) is characterized by compression of left common iliac vein (LCIV) by the overlying right common iliac artery (RCIA). We described an underestimated type of IVCS with dual compression by right and left common iliac arteries (LCIA) simultaneously. Thirty-one patients with IVCS were retrospectively included. All patients received trans-catheter venography and computed tomography (CT) examinations for diagnosing and evaluating IVCS. Late venography and reconstructed CT were used for evaluating the anatomical relationship among LCIV, RCIA and LCIA. Imaging manifestations as well as demographic data were collected and evaluated by two experienced radiologists. Sole and dual compression were found in 32.3% (n = 10) and 67.7% (n = 21) of 31 patients respectively. No statistical differences existed between them in terms of age, gender, LCIV diameter at the maximum compression point, pressure gradient across stenosis, and the percentage of compression level. On CT and venography, sole compression was commonly presented with a longitudinal compression at the orifice of LCIV while dual compression was usually presented as two types: one had a lengthy stenosis along the upper side of LCIV and the other was manifested by a longitudinal compression near to the orifice of external iliac vein. The presence of dual compression seemed significantly correlated with the tortuous LCIA (p = 0.006). Left common iliac vein can be presented by dual compression. This type of compression has typical manifestations on late venography and CT.

  7. Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case.

    PubMed

    Schaefer, F; Anderson, C; Can, B; Say, B

    1998-01-23

    We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome. The patient was found to have a G to T mutation in codon 290 exon 7 of the FGFR2 gene leading to a substitution of a cys for the normal trp at this locus. This is the third mutation characterized at this codon; therefore, this locus appears to be a mutational hotspot in the gene. However, the other known mutations lead to a milder, Crouzon-like phenotype. The introduction of an additional cys into a region characterized by immunoglobulin-type loops maintained by cys S-S crosslinking may provide an explanation for the severity of the clinical findings of this child.

  8. A case of autoimmune urticaria accompanying autoimmune polyglandular syndrome type III associated with Hashimoto's disease, type 1 diabetes mellitus, and vitiligo.

    PubMed

    Kasznicki, Jacek; Drzewoski, Józef

    2014-01-01

    We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.

  9. Pathogenicity of three type 2 Porcine Reproductive and Respiratory Syndrome virus strains in experimentally inoculated pregnant gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanisms of reproductive failure resulting from infection with porcine reproductive and respiratory syndrome virus (PRRSv) are still poorly understood. The present study, a side-by-side evaluation of the pathogenicity of three type 2 PRRSv strains in a reproductive model, was used as a pilot study...

  10. Strategies and Considerations for Teaching an Adolescent with Down Syndrome and Type I Diabetes to Self-Administer Insulin.

    ERIC Educational Resources Information Center

    Bosner, Sylvia M.; Belfiore, Phillip J.

    2001-01-01

    In this study, a system of least prompts, partial participation, and parental involvement was used to successfully teach an adolescent with Down syndrome, moderate mental retardation, and Type I diabetes to self-administer an injection of insulin as part of an overall plan to increase self-determination and independence. (Contains seven…

  11. A Review of College-Level Health Textbooks for Coverage of Type 2 Diabetes, Prediabetes, and Metabolic Syndrome

    ERIC Educational Resources Information Center

    Ethan, Danna; Rennis, Lesley; Samuel, Lalitha; Seidel, Erica J.; Basch, Corey H.

    2014-01-01

    Objective: Type 2 diabetes, prediabetes, and metabolic syndrome are increasingly relevant health problems for United States (US) college-aged students and their family members. This study's aim was to determine the extent to which these chronic conditions were covered in leading college-level personal health textbooks and to what degree the…

  12. Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.

    PubMed

    Deng, Yao; Wei, Shijie; Hu, Shijun; Chen, Jinlan; Tan, Zhiping; Yang, Yifeng

    2015-07-01

    Ehlers-Danlos syndrome type IV is an autosomal dominant connective tissue disease. Mutations in COL3A1 have been identified to underlie this disease; however, to the best of our knowledge, no COL3A1 mutations have been reported in Ehlers-Danlos syndrome type IV patients with an ascending aortic aneurysm. In order to develop further understanding of COL3A1 mutations, an Ehlers-Danlos syndrome type IV patient diagnosed with an ascending aortic aneurysm and a familial history of sudden mortality was analyzed. Genomic DNA was isolated from the peripheral blood of the patient and his family members. All coding exons of eight aneurysm-related genes (FBN1, TGFBR1, TGFBR 2, MYH11, ACTA2, SLC2A10, NOTCH1 and COL3A1) were amplified using polymerase chain reaction (PCR). The PCR products were sequenced with the ABI 3100 Genetic Analyzer, and a mutation was predicted and identified using Polyphen-2, SIFT and Mutation Taster. The novel mutation was identified as c.2950G>A in COL3A1, which results in p.G984R. All three programs predicted this mutation to be deleterous to the protein function. The novel mutation identified in this study is potentially responsible for Ehlers-Danlos syndrome type IV in this patient, and expands the spectrum of COL3A1 mutations.

  13. Aspects of speech-language abilities are influenced by MECP2 mutation type in girls with Rett syndrome.

    PubMed

    Urbanowicz, Anna; Downs, Jenny; Girdler, Sonya; Ciccone, Natalie; Leonard, Helen

    2015-02-01

    This study investigates relationships between methyl-CpG-binding protein 2 gene (MECP2) mutation type and speech-language abilities in girls with Rett syndrome. Cross-sectional data on 766 girls, aged 15 years and under, with genetically confirmed Rett syndrome was obtained from the Australian Rett Syndrome Database (ARSD) (n = 244) and the International Rett Syndrome Phenotype Database (InterRett) (n = 522). Relationships between MECP2 mutation type and age of regression in speech-language abilities, and the level of speech-language abilities before and after this regression were investigated. The females had a median age of 4.95 years in the ARSD and 5.25 years in InterRett. The majority (89%, 685/766) acquired speech-language abilities in the form of babble or words at some point in time. Of those who acquired babble or words, 85% (581/685) experienced a regression in these abilities. Those with a p.Arg133Cys mutation were the most likely to use one or more words, prior to (RRR = 3.45; 95% CI 1.15-10.41) and after (RRR = 5.99; 95% CI 2.00-17.92), speech-language regression. Girls with Rett syndrome vary in their use of speech and language, and in their experience of speech-language regression and these variations are partly explained by genotype.

  14. Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Castori, Marco; Morlino, Silvia; Celletti, Claudia; Ghibellini, Giulia; Bruschini, Michela; Grammatico, Paola; Blundo, Carlo; Camerota, Filippo

    2013-12-01

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes. Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale. In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors' experience. Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders). The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT. Symptoms' clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies.

  15. Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome

    PubMed Central

    Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema

    2017-01-01

    Introduction Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Methods Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Results Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. Conclusion A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort. PMID:28288174

  16. A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2.

    PubMed

    Fauth, Christine; Steindl, Katharina; Toutain, Annick; Farrell, Sandra; Witsch-Baumgartner, Martina; Karall, Daniela; Joset, Pascal; Böhm, Sebastian; Baumer, Alessandra; Maier, Oliver; Zschocke, Johannes; Weksberg, Rosanna; Marshall, Christian R; Rauch, Anita

    2016-02-01

    Hypomorphic germline mutations in the PIGA (phosphatidylinositol glycan class A) gene recently were recognized as the cause of a clinically heterogeneous spectrum of X-linked disorders including (i) early onset epileptic encephalopathy with severe muscular hypotonia, dysmorphism, multiple congenital anomalies, and early death ("MCAHS2"), (ii) neurodegenerative encephalopathy with systemic iron overload (ferro-cerebro-cutaneous syndrome, "FCCS"), and (iii) intellectual disability and seizures without dysmorphism. Previous studies showed that the recurrent PIGA germline mutation c.1234C>T (p.Arg412*) leads to a clinical phenotype at the most severe end of the spectrum associated with early infantile lethality. We identified three additional individuals from two unrelated families with the same PIGA mutation. Major clinical findings include early onset intractable epileptic encephalopathy with a burst-suppression pattern on EEG, generalized muscular hypotonia, structural brain abnormalities, macrocephaly and increased birth weight, joint contractures, coarse facial features, widely spaced eyes, a short nose with anteverted nares, gingival overgrowth, a wide mouth, short limbs with short distal phalanges, and a small penis. Based on the phenotypic overlap with Simpson-Golabi-Behmel syndrome type 2 (SGBS2), we hypothesized that both disorders might have the same underlying cause. We were able to confirm the same c.1234C>T (p.Arg412*) mutation in the DNA sample from an affected fetus of the original family affected with SGBS2. We conclude that the recurrent PIGA germline mutation c.1234C>T leads to a recognizable clinical phenotype with a poor prognosis and is the cause of SGBS2.

  17. Safety of "pain exposure" physical therapy in patients with complex regional pain syndrome type 1.

    PubMed

    van de Meent, Hendrik; Oerlemans, Margreet; Bruggeman, Almar; Klomp, Frank; van Dongen, Robert; Oostendorp, Rob; Frölke, Jan Paul

    2011-06-01

    "Pain exposure" physical therapy (PEPT) is a new treatment for patients with complex regional pain syndrome type 1 (CRPS-1) that consists of a progressive-loading exercise program and management of pain-avoidance behavior without the use of specific CRPS-1 medication or analgesics. The aim of this study was to investigate primarily whether PEPT could be applied safely in patients with CRPS-1. Twenty patients with CRPS-1 were consecutively enrolled in the study after giving informed consent. The diagnosis of CRPS-1 was defined using the Bruehl and Harden/IASP diagnostic criteria. CRPS-1 was diagnosed between 3 and 18 months after the inciting event (trauma). According to a multiple single-case design (baseline [A1], treatment [B], follow-up [A2]), multiple baseline and follow-up measurements were performed to evaluate changes in CRPS signs and symptoms and to assess functional parameters. When comparing the baseline with the follow-up phase, patients improved significantly with respect to pain on the visual analogue scale (57%), pain intensity (48%), muscle strength (52%), arm/shoulder/hand disability (36%), 10-meter walking speed (29%), pain disability index (60%), kinesiophobia (18%), and the domains of perceived health change in the SF-36 survey (269%). Three patients initially showed increased vegetative signs but improved in all other CRPS parameters and showed good functional recovery at follow-up. We conclude that PEPT is a safe and effective treatment for patients with CRPS-1. A progressive-loading exercise program and management of pain-avoidance behavior without the use of specific medication ("pain exposure" physical therapy) is safe and effective for patients with complex regional pain syndrome.

  18. Restless Leg Syndrome in Different Types of Demyelinating Neuropathies: A Single-Center Pilot Study

    PubMed Central

    Luigetti, Marco; Del Grande, Alessandra; Testani, Elisa; Bisogni, Giulia; Losurdo, Anna; Giannantoni, Nadia Mariagrazia; Mazza, Salvatore; Sabatelli, Mario; Della Marca, Giacomo

    2013-01-01

    Objective: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Results: Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Citation: Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949. PMID:23997707

  19. Haemorrhagic bowel syndrome in dairy cattle: possible role of Clostridium perfringens type A in the disease complex.

    PubMed

    Ceci, L; Paradies, P; Sasanelli, M; de Caprariis, D; Guarda, F; Capucchio, M T; Carelli, G

    2006-12-01

    A survey based on clinical, pathological and microbiological investigations was performed on 11 Brown Swiss cattle affected with depression, anorexia, agalaxia, ruminal hypomotility, abdominal pain and melaena. In eight animals, macroscopical lesions consisted in haemorrhagic enteritis in the small intestine. Seven of eight isolates from tissue samples were identified as Clostridum perfringens type A, and four were identified as C. perfringens type A with the beta2 toxin gene. Based on these observations, animals were considered affected with haemorrhagic bowel syndrome.

  20. Urinary pyridinoline cross-links in Ehlers-Danlos syndrome type VI

    SciTech Connect

    Steinmann, B.; Eyre, D.R.; Shao, P. |

    1995-12-01

    The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable disorders of connective tissue, affecting skin, ligaments, joints, blood vessels, and internal organs. The main general findings are hyperextensibility and bruisability of the skin, with abnormal scarring, and joint laxity. On the basis of clinical, genetic, and biochemical findings, EDS can be classified today into at least 10 different types. Among them, EDS type VI (MIM 225400) is characterized by marked muscular hypotonia from birth; kyphoscoliosis, often present at birth and progressing to a severe form; marfanoid habitus; eye involvement, often with microcornea and a tendency of the eyeballs to rupture after minor trauma; osteoporosis; and sometimes spontaneous rupture of arteries. The disorder is due to a deficiency of lysyl hydroxylase (E.C.1.14.11.4), inherited in an autosomal recessive mode. Traditionally, the clinical diagnosis is confirmed by an insufficiency of hydroxylysine, on analysis of hydrolyzed dermis and/or reduced enzyme activity in cultured skin fibroblasts. 12 refs., 1 tab.

  1. Different types of androgen receptor mutations in patients with complete androgen insensitivity syndrome.

    PubMed

    Shao, Jialiang; Hou, Jiangang; Li, Bingkun; Li, Dongyang; Zhang, Ning; Wang, Xiang

    2015-02-01

    Mutations of androgen receptor (AR) are the most frequent cause of 46, XY disorders of sex development and associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome (CAIS)) to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). From 2009 to 2012, two young Chinese female individuals with CAIS from two families were referred to our hospital due to primary amenorrhea. Defects in testosterone (T) and dihydrotestosterone (DHT) synthesis were excluded. Physical examination revealed that the patients have normal female external genitalia, normal breast development, vellus hair in the axilla and on the arms and legs, but absence of pubic hair, and a blind-ending vagina. Two different types of AR mutations have been detected by sequencing of genomic DNA: Family A showed deletion of exon 2 in AR gene; Family B showed a single nucleotide C-to-T transition in exon 8 of AR gene resulting in a proline 893-to-leucine substitution (Pro893Leu). Testicular histology showed developmental immaturity of seminiferous tubules with the absence of spermatogenic cells or spermatozoa. No AR immunoreactivity was observed in either case. Three adult patients recovered well from bilateral orchiectomy. The juvenile patient of family B was followed up. Our present study on these two families revealed two different types of AR mutation. The definitive diagnosis of AIS was based on clinical examination and genetic investigations. Our findings verified the mechanism of CAIS and also enriched AR Gene Mutation Database.

  2. Improvements in long term phototherapy for patients with Crigler-Najjar syndrome type I.

    PubMed

    Job, H; Hart, G; Lealman, G

    1996-11-01

    Patients with Crigler-Najjar syndrome Type I are being treated with long-term blue-light phototherapy into childhood, adolescence and beyond. Phototherapy systems adapted from sunbed-type bases fitted with blue-emitting fluorescent tubes have been described. These systems provided higher irradiances and improved patient compliance compared with overhead therapy systems used in neonatal phototherapy. The acrylic bases of such units are, however, not designed to provide adequate levels of comfort for prolonged treatment in the long term. Previous work has shown that layer(s) of transparent 'bubble-wrap' can be used to address this problem, although the material absorbs light and provides lower levels of comfort for older or larger patients. We have used designs of transparent plastic lilos that provide better cushioning, although tend to puncture, and share with bubble-wrap a low porosity leading to patient discomfort. We have investigated the use of standard mesh and high-transmission fabrics stretched over an adjustable-tension frame. This method in particular combines a high degree of comfort with a clinically effective blue-light irradiance level, and hence appears to provide a satisfactory method of phototherapy delivery. The development of higher transmission materials offers further potential for improvement.

  3. The type specimen (LB1) of Homo floresiensis did not have Laron syndrome.

    PubMed

    Falk, Dean; Hildebolt, Charles; Smith, Kirk; Jungers, William; Larson, Susan; Morwood, Michael; Sutikna, Thomas; Jatmiko; Saptomo, E Wahyu; Prior, Fred

    2009-09-01

    The type specimen (LB1) of Homo floresiensis has been hypothesized to be a pathological human afflicted with Laron Syndrome (LS), a type of primary growth hormone insensitivity (Hershkovitz et al.: Am J Phys Anthropol 134 [2007] 198-208). Comparing measurements, photographs and three-dimensional, computed-tomography reconstructions of LB1 with data and diagnoses from the literature on LS, we critically evaluate numerous skull and postcranial traits that Hershkovitz et al. identified as being shared by LB1 and patients with LS. The statements regarding most of these traits are new to the clinical literature and lack quantitative support. LB1 and patients with LS differ markedly in the size and shape of the cranium; thickness and pneumatization of cranial bones; morphology of the face, mandible, teeth, and chin; form of the shoulder, wrist, and pelvis; and general body proportions including relative foot size. Claims that patients with LS are similar to LB1 in displaying protracted scapulae, short clavicles, low degrees of humeral torsion, flaring ilia, and curved tibiae are not supported by data or corroborating images. Some points of similarity (e.g., femoral neck-shaft angle, femoral bicondylar angle, and estimated stature) can be found in other hominins, and cannot be considered diagnostic. From our review and analysis, we conclude that LB1 did not suffer from LS.

  4. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

    PubMed

    Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul

    2014-08-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

  5. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

    PubMed Central

    Mitra, Arijit; Ramakrishnan, R.; Kader, Mohideen Abdul

    2014-01-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

  6. MFAP5 Loss-of-Function Mutations Underscore the Involvement of Matrix Alteration in the Pathogenesis of Familial Thoracic Aortic Aneurysms and Dissections

    PubMed Central

    Barbier, Mathieu; Gross, Marie-Sylvie; Aubart, Mélodie; Hanna, Nadine; Kessler, Ketty; Guo, Dong-Chuan; Tosolini, Laurent; Ho-Tin-Noe, Benoit; Regalado, Ellen; Varret, Mathilde; Abifadel, Marianne; Milleron, Olivier; Odent, Sylvie; Dupuis-Girod, Sophie; Faivre, Laurence; Edouard, Thomas; Dulac, Yves; Busa, Tiffany; Gouya, Laurent; Milewicz, Dianna M.; Jondeau, Guillaume; Boileau, Catherine

    2014-01-01

    Thoracic aortic aneurysm and dissection (TAAD) is an autosomal-dominant disorder with major life-threatening complications. The disease displays great genetic heterogeneity with some forms allelic to Marfan and Loeys-Dietz syndrome, and an important number of cases still remain unexplained at the molecular level. Through whole-exome sequencing of affected members in a large TAAD-affected family, we identified the c.472C>T (p.Arg158∗) nonsense mutation in MFAP5 encoding the extracellular matrix component MAGP-2. This protein interacts with elastin fibers and the microfibrillar network. Mutation screening of 403 additional probands identified an additional missense mutation of MFAP5 (c.62G>T [p.Trp21Leu]) segregating with the disease in a second family. Functional analyses performed on both affected individual’s cells and in vitro models showed that these two mutations caused pure or partial haploinsufficiency. Thus, alteration of MAGP-2, a component of microfibrils and elastic fibers, appears as an initiating mechanism of inherited TAAD. PMID:25434006

  7. MFAP5 loss-of-function mutations underscore the involvement of matrix alteration in the pathogenesis of familial thoracic aortic aneurysms and dissections.

    PubMed

    Barbier, Mathieu; Gross, Marie-Sylvie; Aubart, Mélodie; Hanna, Nadine; Kessler, Ketty; Guo, Dong-Chuan; Tosolini, Laurent; Ho-Tin-Noe, Benoit; Regalado, Ellen; Varret, Mathilde; Abifadel, Marianne; Milleron, Olivier; Odent, Sylvie; Dupuis-Girod, Sophie; Faivre, Laurence; Edouard, Thomas; Dulac, Yves; Busa, Tiffany; Gouya, Laurent; Milewicz, Dianna M; Jondeau, Guillaume; Boileau, Catherine

    2014-12-04

    Thoracic aortic aneurysm and dissection (TAAD) is an autosomal-dominant disorder with major life-threatening complications. The disease displays great genetic heterogeneity with some forms allelic to Marfan and Loeys-Dietz syndrome, and an important number of cases still remain unexplained at the molecular level. Through whole-exome sequencing of affected members in a large TAAD-affected family, we identified the c.472C>T (p.Arg158(∗)) nonsense mutation in MFAP5 encoding the extracellular matrix component MAGP-2. This protein interacts with elastin fibers and the microfibrillar network. Mutation screening of 403 additional probands identified an additional missense mutation of MFAP5 (c.62G>T [p.Trp21Leu]) segregating with the disease in a second family. Functional analyses performed on both affected individual's cells and in vitro models showed that these two mutations caused pure or partial haploinsufficiency. Thus, alteration of MAGP-2, a component of microfibrils and elastic fibers, appears as an initiating mechanism of inherited TAAD.

  8. QT Dynamics During Exercise in Asymptomatic Children with Long QT Syndrome Type 3.

    PubMed

    Takahashi, Kazuhiro; Nabeshima, Taisuke; Nakayashiro, Mami; Ganaha, Hitoshi

    2016-06-01

    Sympathetic provocative testing is commonly used to detect the abnormal QT dynamics in long QT syndrome (LQTS) patients, particularly LQTS type 1 and type 2. However, little is known about LQTS type 3 (LQT3). We investigated QT dynamics during exercise testing in LQTS patients, particularly LQT3. This study included 37 subjects, comprising 16 genotyped LQTS patients and 21 unrelated healthy subjects without QT prolongation. LQTS patients were divided into LQT3 and non-LQT3 groups. During exercise tests using a modified Bruce protocol, 12-lead electrocardiogram monitoring was performed using a novel multifunctional electrocardiograph. QT intervals were automatically measured. The QT/heart rate (HR) relationship was visualized by plotting the beat-to-beat confluence of the recorded data. A linear regression analysis was performed to determine the QT/HR slope and intercept. Estimated QT intervals at HR 60 bpm (QT60) were calculated by the regression line formula. QT/HR slopes were steeper for each LQTS group than for the control group (P < 0.001). QT60 values demonstrated a moderate correlation with QT intervals at rest (P < 0.0001) for both groups. The corrected QT intervals (QTc) at 4 min of recovery after exercise were significantly longer in the non-LQT3 group than in the control group but were not different between the LQT3 and the control groups. Abnormal QT dynamics during exercise testing were observed in both LQT3 patients and other LQTS subtypes. This method may be useful for directing genetic testing in subjects with borderline prolonged QT intervals.

  9. The Phenotype of the Musculocontractural Type of Ehlers-Danlos Syndrome due to CHST14 Mutations

    PubMed Central

    Janecke, Andreas R.; Li, Ben; Boehm, Manfred; Krabichler, Birgit; Rohrbach, Marianne; Müller, Thomas; Fuchs, Irene; Golas, Gretchen; Katagiri, Yasuhiro; Ziegler, Shira G.; Gahl, William A.; Wilnai, Yael; Zoppi, Nicoletta; Geller, Herbert M.; Giunta, Cecilia; Slavotinek, Anne; Steinmann, Beat

    2016-01-01

    The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with biallelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients hadmildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS. PMID:26373698

  10. Effects of carpal tunnel syndrome on dexterous manipulation are grip type-dependent.

    PubMed

    Zhang, Wei; Johnston, Jamie A; Ross, Mark A; Sanniec, Kyle; Gleason, Elizabeth A; Dueck, Amylou C; Santello, Marco

    2013-01-01

    Carpal tunnel syndrome (CTS) impairs sensation of a subset of digits. Although the effects of CTS on manipulation performed with CTS-affected digits have been studied using precision grip tasks, the extent to which CTS affects multi-digit force coordination has only recently been studied. Whole-hand manipulation studies have shown that CTS patients retain the ability to modulate multi-digit forces to object mass, mass distribution, and texture. However, CTS results in sensorimotor deficits relative to healthy controls, including significantly larger grip force and lower ability to balance the torques generated by the digits. Here we investigated the effects of CTS on multi-digit force modulation to object weight when manipulating an object with a variable number of fingers. We hypothesized that CTS patients would be able to modulate digit forces to object weight. However, as different grip types involve the exclusive use of CTS-affected digits ('uniform' grips) or a combination of CTS-affected and non-affected digits ('mixed' grips), we addressed the question of whether 'mixed' grips would reduce or worsen CTS-induced force coordination deficits. The former scenario would be due to adding digits with intact tactile feedback, whereas the latter scenario might occur due to a potentially greater challenge for the central nervous system of integrating 'noisy' and intact tactile feedback. CTS patients learned multi-digit force modulation to object weight regardless of grip type. Although controls exerted the same total grip force across all grip types, patients exerted significantly larger grip force than controls but only for manipulations with four and five digits. Importantly, this effect was due to CTS patients' inability to change the finger force distribution when adding the ring and little fingers. These findings suggest that CTS primarily challenges sensorimotor integration processes for dexterous manipulation underlying the coordination of CTS-affected and non

  11. Effects of Carpal Tunnel Syndrome on Dexterous Manipulation Are Grip Type-Dependent

    PubMed Central

    Zhang, Wei; Johnston, Jamie A.; Ross, Mark A.; Sanniec, Kyle; Gleason, Elizabeth A.; Dueck, Amylou C.; Santello, Marco

    2013-01-01

    Carpal tunnel syndrome (CTS) impairs sensation of a subset of digits. Although the effects of CTS on manipulation performed with CTS-affected digits have been studied using precision grip tasks, the extent to which CTS affects multi-digit force coordination has only recently been studied. Whole-hand manipulation studies have shown that CTS patients retain the ability to modulate multi-digit forces to object mass, mass distribution, and texture. However, CTS results in sensorimotor deficits relative to healthy controls, including significantly larger grip force and lower ability to balance the torques generated by the digits. Here we investigated the effects of CTS on multi-digit force modulation to object weight when manipulating an object with a variable number of fingers. We hypothesized that CTS patients would be able to modulate digit forces to object weight. However, as different grip types involve the exclusive use of CTS-affected digits (‘uniform’ grips) or a combination of CTS-affected and non-affected digits (‘mixed’ grips), we addressed the question of whether ‘mixed’ grips would reduce or worsen CTS-induced force coordination deficits. The former scenario would be due to adding digits with intact tactile feedback, whereas the latter scenario might occur due to a potentially greater challenge for the central nervous system of integrating ‘noisy’ and intact tactile feedback. CTS patients learned multi-digit force modulation to object weight regardless of grip type. Although controls exerted the same total grip force across all grip types, patients exerted significantly larger grip force than controls but only for manipulations with four and five digits. Importantly, this effect was due to CTS patients’ inability to change the finger force distribution when adding the ring and little fingers. These findings suggest that CTS primarily challenges sensorimotor integration processes for dexterous manipulation underlying the coordination of CTS

  12. The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations.

    PubMed

    Janecke, Andreas R; Li, Ben; Boehm, Manfred; Krabichler, Birgit; Rohrbach, Marianne; Müller, Thomas; Fuchs, Irene; Golas, Gretchen; Katagiri, Yasuhiro; Ziegler, Shira G; Gahl, William A; Wilnai, Yael; Zoppi, Nicoletta; Geller, Herbert M; Giunta, Cecilia; Slavotinek, Anne; Steinmann, Beat

    2016-01-01

    The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with bi-allelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients had mildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS.

  13. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome.

    PubMed

    Budny, Bartlomiej; Chen, Wei; Omran, Heymut; Fliegauf, Manfred; Tzschach, Andreas; Wisniewska, Marzena; Jensen, Lars R; Raynaud, Martine; Shoichet, Sarah A; Badura, Magda; Lenzner, Steffen; Latos-Bielenska, Anna; Ropers, Hans-Hilger

    2006-09-01

    We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral-facial-digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.

  14. Tandem duplication within a Neurofibromatosis type I (NFI) gene exon in a family with features of Watson syndrome and Noonan syndrome

    SciTech Connect

    Tassabehji, M.; Strachan, T.; Colley, A.; Donnai, D.; Harris, R.; Thakker, N. ); Sharland, M )

    1993-07-01

    Type 1 neurofibromatosis (NF1), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or the phenotypes arise from mutations in very closely linked genes. Here the authors provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication of 42 bases in exon 28 of the NF1 gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product. 31 refs., 2 figs.

  15. Tandem duplication within a neurofibromatosis type 1 (NF1) gene exon in a family with features of Watson syndrome and Noonan syndrome.

    PubMed Central

    Tassabehji, M; Strachan, T; Sharland, M; Colley, A; Donnai, D; Harris, R; Thakker, N

    1993-01-01

    Type 1 neurofibromatosis (NF1), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or that phenotypes arise from mutations in very closely linked genes. Here we provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication of 42 bases in exon 28 of the NF1 gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product. Images Figure 1 Figure 2 PMID:8317503

  16. Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm.

    PubMed

    García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

    2013-01-01

    The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.

  17. The clinical relevance of complex regional pain syndrome type I: The Emperor's New Clothes.

    PubMed

    Borchers, Andrea T; Gershwin, M Eric

    2017-01-01

    The management of patients with chronic pain is a nearly daily challenge to rheumatologists, neurologists, orthopedic surgeons, pain specialists and indeed a issue in nearly every clinical practice. Among the myriad of causes of pain are often included a unique syndrome, generally referred to as complex regional pain syndrome type I (CRPS). Unfortunately CRPS I has become a catch all phase and there are serious questions on whether it exists at all; this has led to an extraordinary number of poorly defined diagnostic criteria. It has also led to an etiologic quagmire that includes features as diverse as autoimmunity to simple trauma. These, in turn, have led to overdiagnosis and often overzealous use of pain medications, including narcotics. In a previous paper, we raised the issue of whether CRPS type I reflected a valid diagnosis. Indeed, the diagnostic criteria for CRPS I, and therefore the diagnosis itself, is unreliable for a number of reasons: 1) the underlying pathophysiology of the signs and symptoms of CPRS I are not biologically plausible; 2) there are no consistent laboratory or imaging testing available; 3) the signs and symptoms fluctuate over time without a medical explanation; 4) the definitions of most studies are derived from statistical analysis with little consideration to required sample size, i.e. power calculations; 5) interobserver reliability in the assessment of the signs and symptoms are often only fair to moderate, and agreement on the diagnosis of "CRPS I" is poor. Even physicians who still believe in the concept of "CRPS I" admit that it is vastly overdiagnosed and has become a diagnosis of last resort, often without a complete differential diagnosis and an alternative explanation. Finally, one of the most convincing arguments that there is no clinical entity as "CRPS I" comes from the enormous heterogeneity in sign and symptom profiles and the heterogeneity of pathophysiological mechanisms postulated. This observation is underscored by

  18. A Type A and Type D Combined Personality Typology in Essential Hypertension and Acute Coronary Syndrome Patients: Associations with Demographic, Psychological, Clinical, and Lifestyle Indicators

    PubMed Central

    Steca, Patrizia; D’Addario, Marco; Magrin, Maria Elena; Miglioretti, Massimo; Monzani, Dario; Pancani, Luca; Sarini, Marcello; Scrignaro, Marta; Vecchio, Luca; Fattirolli, Francesco; Giannattasio, Cristina; Cesana, Francesca; Riccobono, Salvatore Pio

    2016-01-01

    Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed. PMID:27589065

  19. Fluency Disorders in Genetic Syndromes

    ERIC Educational Resources Information Center

    Van Borsel, John; Tetnowski, John A.

    2007-01-01

    The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of…

  20. De Novo 17q paracentric inversion mosaicism in a patient with beemer-langer type short rib-polydactyly syndrome with special consideration to the classification of short rib polydactyly syndromes

    SciTech Connect

    Chen, H.; Mirkin, D.; Yang, S.

    1994-11-01

    A de novo 17q paracentric inversion mosaicism is detected in a fetus with type IV short rib (polydactyly) syndrome (Beemer-Langer). The cytogenetic finding in our case suggests a possible location of the gene or cluster of linked genes responsible for SR (P) S type IV to 17q21 or 17q23. Since this chromosome abnormality has not been described in short rib polydactyly syndromes and the existence of type IV SR (P) S has been controversial, the literature of this entity is reviewed with special consideration to the classification of short rib polydactyly syndromes. 28 refs., 5 figs., 1 tab.

  1. Genetic linkage analysis of hereditary arthro-ophthalmopathy (Stickler syndrome) and the type II procollagen gene.

    PubMed Central

    Knowlton, R G; Weaver, E J; Struyk, A F; Knobloch, W H; King, R A; Norris, K; Shamban, A; Uitto, J; Jimenez, S A; Prockop, D J

    1989-01-01

    Hereditary arthro-ophthalmopathy (AO), or Stickler syndrome, is a dominantly inherited disorder characterized by vitreo-retinal degeneration and frequently accompanied by epiphyseal dysplasia and premature degenerative joint disease. Three large families with AO were analyzed for clinical manifestations of the disease and for coinheritance of the genetic defect with RFLPs in the type II procollagen gene (COL2A1). Genetic linkage between AO and COL2A1 was demonstrated in the largest family, with a maximum LOD score of 3.52 at a recombination distance of zero. Data from a second family also supported linkage of AO and COL2A1, with a LOD score of 1.20 at a recombination distance of zero. These results are consistent with the conclusion that mutations in the COL2A1 gene are responsible for AO in these two families. In a third AO family, however, recombination between AO and COL2A1 occurred in at least one meiosis, and the data were inconclusive with respect to linkage. Images Figure 2 PMID:2573273

  2. Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases

    PubMed Central

    Rodgers, Kyla R.; Gui, Jiang; Dinulos, Mary Beth P.; Chou, Richard C.

    2017-01-01

    We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup (NWU, 9.2%; LWU, 33.3%, CWU, 67.1%; p-value < 0.0001). The HLA-B27 antigen was more prevalent (p-value < 2.2 × 10–8) in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible. PMID:28051109

  3. Molecular findings of Colombian patients with type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)

    PubMed Central

    Giraldo, Gustavo Adolfo; Ayala-Ramírez, Paola; Prieto, Juan Carlos; García-Robles, Reggie; Acosta, Johanna Carolina

    2015-01-01

    Introduction Maroteaux–Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients. Results Fourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.*534W, p.S334I, p.H147P, c.900T > G, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1G > C). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious. Conclusions Most of the Colombian patients in this study had private mutations. PMID:26909334

  4. Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome

    PubMed Central

    Kashima, Risa; Roy, Sougata; Ascano, Manuel; Martinez-Cerdeno, Veronica; Ariza-Torres, Jeanelle; Kim, Sunghwan; Louie, Justin; Lu, Yao; Leyton, Patricio; Bloch, Kenneth D.; Kornberg, Thomas B.; Hagerman, Paul J.; Hagerman, Randi; Lagna, Giorgio; Hata, Akiko

    2017-01-01

    Epigenetic silencing of fragile X mental retardation 1 (FMR1) causes fragile X syndrome (FXS), a common inherited form of intellectual disability and autism. FXS correlates with abnormal synapse and dendritic spine development, but the molecular link between the absence of the FMR1 product FMRP, an RNA binding protein, and the neuropathology is unclear. We found that the messenger RNA encoding bone morphogenetic protein type II receptor (BMPR2) is a target of FMRP. Depletion of FMRP increased BMPR2 abundance, especially that of the full-length isoform that bound and activated LIM domain kinase 1 (LIMK1), a component of the noncanonical BMP signal transduction pathway that stimulates actin reorganization to promote neurite outgrowth and synapse formation. Heterozygosity for BMPR2 rescued the morphological abnormalities in neurons both in Drosophila and in mouse models of FXS, as did the postnatal pharmacological inhibition of LIMK1 activity. Compared with postmortem prefrontal cortex tissue from healthy subjects, the amount of full-length BMPR2 and of a marker of LIMK1 activity was increased in this brain region from FXS patients. These findings suggest that increased BMPR2 signal transduction is linked to FXS and that the BMPR2-LIMK1 pathway is a putative therapeutic target in patients with FXS and possibly other forms of autism. PMID:27273096

  5. An Atypical Presentation of a Male with Oral-Facial-Digital Syndrome Type 1 Related Ciliopathy

    PubMed Central

    Goldberg, Ethan M.; Reynoso, Francis Jeshira; Pradhan, Madhura

    2016-01-01

    Background. Oral-facial-digital syndrome type 1 (OFD1) is a rare condition with X-linked dominant inheritance caused by mutations in the Cxorf5 (OFD1) gene. This gene encodes the OFD1 protein located within centrosomes and basal bodies of primary cilia. Approximately 15–50% of patients with OFD1 progress to end-stage kidney disease following development of polycystic changes within the kidneys. This condition almost always causes intrauterine lethality in males. Description of Case Diagnosis and Treatment. A Caucasian male aged 9 years and 9 months presented with increased urinary frequency, increased thirst, and decreased appetite. Physical examination demonstrated short stature, hearing loss, photophobia, murmur, and hypogonadism. He had no other dysmorphic features. Laboratory results revealed anemia, renal insufficiency, and dilute urine with microscopic hematuria but no proteinuria. Ultrasound showed small kidneys with increased echogenicity but no evidence of cystic changes. A Ciliopathy Panel showed a novel and likely pathogenic deletion, approximately 7.9 kb, in the OFD1 gene encompassing exons 16, 17, and 19 (c.1654+833_2599+423del). Brain MRI did not demonstrate typical OFD1 findings. He is currently on chronic hemodialysis awaiting transplant from a living donor. Conclusions. We present a male patient with OFD1 mutation who lacks the classic OFD1 phenotype who presented with end-stage renal disease without evidence of polycystic changes within the kidneys. PMID:27651963

  6. Genetic and Phenotypic Heterogeneity in Chinese Patients with Waardenburg Syndrome Type II

    PubMed Central

    Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun

    2013-01-01

    Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients. PMID:24194866

  7. Screening of MITF and SOX10 Regulatory Regions in Waardenburg Syndrome Type 2

    PubMed Central

    Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

    2012-01-01

    Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy. PMID:22848661

  8. Elosulfase Alfa: a review of its use in patients with mucopolysaccharidosis type IVA (Morquio A syndrome).

    PubMed

    Lyseng-Williamson, Katherine A

    2014-10-01

    Elosulfase alfa (Vimizim(®)) is a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) that is lacking in patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). It is the first, and currently only, disease-specific treatment option for this very rare, progressively degenerative, autosomal-recessive lysosomal storage disorder. Enzyme replacement therapy with elosulfase alfa aims to restore GALNS activity, thereby preventing the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in lysosomal compartments of cells that results in the clinical manifestations of MPS IVA. In clinical trials in children and adults with MPS IVA, intravenous elosulfase alfa 2 mg/kg/week provided significant and sustained improvements in urinary levels of KS (a pharmacodynamic biomarker for the disease). In the key placebo-controlled, 24-week, phase 3 trial in patients with MPS IVA aged ≥5 years, elosulfase alfa 2 mg/kg/week significantly improved endurance [least squares mean placebo-adjusted change from baseline in 6-min walk test distance 22.5 m (95 % CI 4.0-40.9)]. Infusion-associated reactions, the primary tolerability issue associated with elosulfase alfa, are generally mild to moderate in severity, self-limiting, and manageable. In the absence of a cure, GALNS enzyme replacement therapy with elosulfase alfa is an important achievement in the treatment of MPS IVA.

  9. A-type lamins and Hutchinson-Gilford progeria syndrome: pathogenesis and therapy.

    PubMed

    Gonzalez, Jose M; Pla, Davinia; Perez-Sala, Dolores; Andres, Vicente

    2011-06-01

    Lamin A and lamin C (A-type lamins, both encoded by the LMNA gene) are major components of the mammalian nuclear lamina, a complex proteinaceous structure that acts as a scaffold for protein complexes that regulate nuclear structure and function. Abnormal accumulation of farnesylated-progerin, a mutant form of prelamin A, plays a key role in the pathogenesis of the Hutchinson-Gilford progeria syndrome (HGPS), a devastating disorder that causes the death of affected children at an average age of 13.5 years, predominantly from premature atherosclerosis and myocardial infarction or stroke. Remarkably, progerin is also present in normal cells and appears to progressively accumulate during aging of non-HGPS cells. Therefore, understanding how this mutant form of lamin A provokes HGPS may shed significant insight into physiological aging. In this review, we discuss recent advances into the pathogenic mechanisms underlying HGPS, the main murine models of the disease, and the therapeutic strategies developed in cellular and animal models with the aim of reducing the accumulation of farnesylated-progerin, as well as their use in clinical trials of HGPS.

  10. Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose.

    PubMed

    Kempf, Kerstin; Rose, Bettina; Herder, Christian; Kleophas, Ursula; Martin, Stephan; Kolb, Hubert

    2006-11-01

    Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

  11. Successful vaginal birth after caesarean section in patient with Ehler-Danlos syndrome type 2.

    PubMed

    Maraj, Hemant; Mohajer, Michelle; Bhattacharjee, Deepannita

    2011-12-01

    We present the case of a 31-year-old woman with Ehler-Danlos syndrome (EDS) type 2. She had a previous caesarean section and went on to have an uncomplicated vaginal birth in her last pregnancy. To our knowledge, this is the first case of a successful vaginal birth after caesarean section in a patient with EDS. EDS is a multisystem disorder involving a genetic defect in collagen and connective-tissue synthesis and structure. It is a heterogeneous group of 11 different inherited disorders. Obstetric complications in these patients include miscarriages, stillbirths, premature rupture of the membranes, preterm labour, uterine prolapse, uterine rupture and severe postpartum haemorrhage. There has been much controversy over the appropriate mode of delivery. Abdominal deliveries are complicated by delayed wound healing and increased perioperative blood loss. Vaginal deliveries may be complicated by tissue friability causing extensive perineal tears, pelvic floor and bladder lesions. Our case highlights that in specific, controlled situations it is possible to have a vaginal delivery even after previous caesarean section in patients with EDS.

  12. Association between brain structural anomalies, electroencephalogram and history of seizures in Mucopolysaccharidosis type II (Hunter syndrome).

    PubMed

    Jiménez-Arredondo, Ramón Ernesto; Brambila-Tapia, Aniel Jessica Leticia; Mercado-Silva, Francisco Miguel; Ortiz-Aranda, Martha; Benites-Godinez, Verónica; Olmos-García-de-Alba, Graciela; Figuera, Luis Eduardo

    2017-03-01

    Mucopolysaccharidosis type II or Hunter syndrome (MPS II) is a genetic disease that can course with intellectual impairment and central nervous system (CNS) alterations. To date, no report has documented electroencephalogram (EEG) measures associated with CNS alterations, detected by imaging studies, and the history of seizures in patients with MPS II. Therefore, we decided to search this association. We included 9 patients with MPS II and performed imaging studies of the brain to detect the presence of cortico-subcortical atrophy, enlarged subarachnoid space and supratentorial ventricular size. Additionally, we performed EEG studies in sleep and awake conditions and a complete clinical description. Five out of the nine patients presented history of seizures and all except one patient (88.9%) presented some CNS structural alteration in the imaging studies, being the most frequent the cortico-subcortical atrophy (77.8%). The EEG results showed low amplitude in all patients and low voltage in sleep condition in eight patients with interhemispheric asymmetry in six patients during awake and sleep conditions. Although the five patients with history of seizures did not present a distinctive EEG anomaly, four of them presented some structural alteration in the imaging studies. In conclusion, most patients presented structural alterations in the CNS; likewise, all of them presented EEG anomalies mainly during sleep conditions. However, a clear association between EEG, CNS and the history of seizures was not established.

  13. Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells

    PubMed Central

    Fontes-Oliveira, Cibely C.; Steinz, Maarten; Schneiderat, Peter; Mulder, Hindrik; Durbeej, Madeleine

    2017-01-01

    Skeletal muscle has high energy requirement and alterations in metabolism are associated with pathological conditions causing muscle wasting and impaired regeneration. Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the LAMA2 gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients. PMID:28367954

  14. Genetic and phenotypic heterogeneity in Chinese patients with Waardenburg syndrome type II.

    PubMed

    Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun

    2013-01-01

    Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.

  15. Ehlers-Danlos syndrome, hypermobility type: A characterization of the patients' lived experience.

    PubMed

    Murray, Brittney; Yashar, Beverly M; Uhlmann, Wendy R; Clauw, Daniel J; Petty, Elizabeth M

    2013-12-01

    Hypermobility type Ehlers-Danlos syndrome (EDS-HT) is an inherited connective tissue disorder clinically diagnosed by the presence of significant joint hypermobility and associated skin manifestations. This article presents a large-scale study that reports the lived experience of EDS-HT patients, the broad range of symptoms that individuals with EDS-HT experience, and the impact these symptoms have on daily functioning. A 237-item online survey, including validated questions regarding pain and depression, was developed. Four hundred sixty-six (466) adults (90% female, 52% college or higher degree) with a self-reported diagnosis of EDS-HT made in a clinic or hospital were included. The most frequently reported symptoms were joint pain (99%), hypermobility (99%), and limb pain (91%). They also reported a high frequency of other conditions including chronic fatigue (82%), anxiety (73%), depression (69%), and fibromyalgia (42%). Forty-six percent of respondents reported constant pain often described as aching and tiring/exhausting. Despite multiple interventions and therapies, many individuals (53%) indicated that their diagnosis negatively affected their ability to work or attend school. Our results show that individuals with EDS-HT can experience a wide array of symptoms and co-morbid conditions. The degree of constant pain and disability experienced by the majority of EDS-HT respondents is striking and illustrates the impact this disorder has on quality of life as well as the clinical challenges inherent in managing this complex connective tissue disorder.

  16. Cognitive skills and reading in adults with Usher syndrome type 2

    PubMed Central

    Henricson, Cecilia; Lidestam, Björn; Lyxell, Björn; Möller, Claes

    2015-01-01

    Objective: To investigate working memory (WM), phonological skills, lexical skills, and reading comprehension in adults with Usher syndrome type 2 (USH2). Design: The participants performed tests of phonological processing, lexical access, WM, and reading comprehension. The design of the test situation and tests was specifically considered for use with persons with low vision in combination with hearing impairment. The performance of the group with USH2 on the different cognitive measures was compared to that of a matched control group with normal hearing and vision (NVH). Study Sample: Thirteen participants with USH2 aged 21–60 years and a control group of 10 individuals with NVH, matched on age and level of education. Results: The group with USH2 displayed significantly lower performance on tests of phonological processing, and on measures requiring both fast visual judgment and phonological processing. There was a larger variation in performance among the individuals with USH2 than in the matched control group. Conclusion: The performance of the group with USH2 indicated similar problems with phonological processing skills and phonological WM as in individuals with long-term hearing loss. The group with USH2 also had significantly longer reaction times, indicating that processing of visual stimuli is difficult due to the visual impairment. These findings point toward the difficulties in accessing information that persons with USH2 experience, and could be part of the explanation of why individuals with USH2 report high levels of fatigue and feelings of stress (Wahlqvist et al., 2013). PMID:25859232

  17. Cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome, and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The metabolic syndrome is associated with insulin resistance, elevated glucose and lipids, inflammation, decreased antioxidant activity, increased weight gain, and increased glycation of proteins. Cinnamon has been shown to improve aspects of metabolic syndrome in cells cultured in vitro, and in an...

  18. Executive Functioning in Children with Asperger Syndrome, ADHD-Combined Type, ADHD-Predominately Inattentive Type, and Controls

    ERIC Educational Resources Information Center

    Semrud-Clikeman, Margaret; Walkowiak, Jenifer; Wilkinson, Alison; Butcher, Brianne

    2010-01-01

    The purpose of the study was to evaluate neuropsychological and behavioral rating measures of executive functions (EF) in children with two subtypes of ADHD, Asperger syndrome (AS), and controls. Relative to the control group, the clinical groups experienced more difficulty in EF. The AS group showed the most difficulty in emotional control,…

  19. A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1

    PubMed Central

    Bruserud, Øyvind; Oftedal, Bergithe E.; Landegren, Nils; Erichsen, Martina M.; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P.; Myhre, Anne G.; Svartberg, Johan; Fougner, Kristian J.; Bakke, Åsne; Nedrebø, Bjørn G.; Mella, Bjarne; Breivik, Lars; Viken, Marte K.; Knappskog, Per M.; Marthinussen, Mihaela C.; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B.

    2016-01-01

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID:27253668

  20. Frontostriatal dysexecutive syndrome: a core cognitive feature of myotonic dystrophy type 2.

    PubMed

    Peric, Stojan; Mandic-Stojmenovic, Gorana; Stefanova, Elka; Savic-Pavicevic, Dusanka; Pesovic, Jovan; Ilic, Vera; Dobricic, Valerija; Basta, Ivana; Lavrnic, Dragana; Rakocevic-Stojanovic, Vidosava

    2015-01-01

    The aim of this study was to assess cognitive status in a large group of patients with myotonic dystrophy type 2 (DM2) compared to type 1 (DM1) subjects matched for gender and age, using a comprehensive battery of neuropsychological tests. Thirty-four genetically confirmed adult DM2 patients were recruited and matched for gender and age with 34 adult-onset DM1 subjects. All patients underwent detailed classic pen and pencil neuropsychological investigation and also computerized automated battery-CANTAB. More than half of DM2 patients had abnormal results on executive tests [Intra/Extradimensional Set Shift (IED), Stockings of Cambridge (SOC)] and verbal episodic memory (Ray Auditory Verbal Learning Test). Regarding DM1, abnormal results in more than 50 % of subjects were achieved in even ten tests, including visuospatial, language, executive, cognitive screening and visual memory tests. Direct comparison between patient groups showed that lower percentage of DM2 patients had abnormal results on following tests: Addenbrooke's Cognitive Examination-Revised, Raven Standard Progressive Matrices, Block Design, copy and recall of Rey-Osterieth Complex Figure, number of categories and perseverative responses on Wisconsin Card Sorting Test and Boston Naming Test (p < 0.01), as well as Trail Making Test-B and Spatial Span (p < 0.05). Our results showed significant dysexecutive syndrome and certain impairment of episodic verbal memory in DM2 patients that are reflective of frontal (especially frontostriatal) and temporal lobe dysfunction. On the other hand, dysexecutive and visuospatial/visuoconstructional deficits predominate in DM1 which correspond to the frontal, parietal (and occipital) lobe dysfunction.

  1. Mucopolysaccharidosis Type IIIA presents as a variant of Klüver–Bucy syndrome

    PubMed Central

    Potegal, Michael; Yund, Brianna; Rudser, Kyle; Ahmed, Alia; Delaney, Kate; Nestrasil, Igor; Whitley, Chester B.; Shapiro, Elsa G.

    2013-01-01

    Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative disease with behavioral symptoms unique among the mucopolysaccharidoses. Children with MPS IIIA reportedly mouth things, explore novel environments almost continuously, disregard danger, and empathize/socialize and comply less with parents. These characteristics resemble Klüver–Bucy syndrome (K-Bs). To test the K-Bs hypothesis, 30 children with MPS IIIA were compared to 8 ‘post-transplant’ Mucopolysaccharidosis type IH patients in an experimental “Risk Room”. The room contained attractive and mildly frightening objects, exposure to a 92 dB startle noise triggered by contact with an attractive toy, mother’s return after a brief absence, and compliance with her clean-up directive. Children with MPS IIIA: 1) left mother sooner, 2) wandered more, 3) were more likely to approach frightening objects, 4) were less likely to respond to loud noise with whole body startle, 5) were less likely to avoid the toy associated with the startle noise, 6) interacted less with mother upon her return, and 7) complied less with her clean-up command. K-Bs is associated with loss of amygdala function. Brain MRIs of a subset of the children with MPS IIIA showed volume loss that was greater in the amygdala than the hippocampus; only amygdala loss correlated with reduced fearfulness. MPS IIIA may be the first identified pediatric disease presenting systematically as a K-Bs variant. If validated by further studies, the K-Bs hypothesis of MPS IIIA would provide important clinical and theoretical information for the guidance of families as well as markers for natural disease progression and treatment effects. PMID:23745734

  2. Mucopolysaccharidosis Type IIIA presents as a variant of Klüver-Bucy syndrome.

    PubMed

    Potegal, Michael; Yund, Brianna; Rudser, Kyle; Ahmed, Alia; Delaney, Kate; Nestrasil, Igor; Whitley, Chester B; Shapiro, Elsa G

    2013-01-01

    Mucopolysaccharidosis Type IIIA (MPS IIIA) is a neurodegenerative disease with behavioral symptoms unique among the mucopolysaccharidoses. Children with MPS IIIA reportedly mouth things, explore novel environments almost continuously, disregard danger, and empathize/socialize and comply less with parents. These characteristics resemble Klüver-Bucy syndrome (K-Bs). To test the K-Bs hypothesis, 30 children with MPS IIIA were compared to 8 "posttransplant" mucopolysaccharidosis Type IH patients in an experimental "risk room." The room contained attractive and mildly frightening objects, exposure to a 92-dB startle noise triggered by contact with an attractive toy, mother's return after a brief absence, and compliance with her cleanup directive. Children with MPS IIIA: (a) left mother sooner, (b) wandered more, (c) were more likely to approach frightening objects, (d) were less likely to respond to loud noise with whole body startle, (e) were less likely to avoid the toy associated with the startle noise, (f) interacted less with mother upon her return, and (g) complied less with her cleanup command. K-Bs is associated with loss of amygdala function. Brain magnetic resonance imaging (MRI) of a subset of the children with MPS IIIA showed volume loss that was greater in the amygdala than in the hippocampus; only amygdala loss correlated with reduced fearfulness. MPS IIIA may be the first identified pediatric disease presenting systematically as a K-Bs variant. If validated by further studies, the K-Bs hypothesis of MPS IIIA would provide important clinical and theoretical information for the guidance of families as well as markers for natural disease progression and treatment effects.

  3. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody.

    PubMed

    Sharma, Chandra Mohan; Pandey, Rajendra Kumar; Kumawat, Banshi Lal; Khandelwal, Dinesh; Gandhi, Pankaj

    2016-01-01

    Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes, limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies. Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome, cerebellar ataxia and palatal myoclonus. This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

  4. Cervical artery dissections and type A aortic dissection in a family with a novel missense COL3A1 mutation of vascular type Ehlers-Danlos syndrome.

    PubMed

    Makrygiannis, Georgios; Loeys, Bart; Defraigne, Jean-Olivier; Sakalihasan, Natzi

    2015-11-01

    Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD as the single manifestation of vEDS. This is a heterozygous c.953G > A mutation in exon 14, disrupting the normal Gly-X-Y repeats of type III procollagen, by converting glycine to aspartic acid.

  5. Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type.

    PubMed

    Chaudhuri, Abanti; Kambham, Neeraja; Sutherland, Scott; Grimm, Paul; Alexander, Steven; Concepcion, Waldo; Sarwal, Minnie; Wong, Cynthia

    2012-08-01

    Congenital nephrotic syndrome (CNS) of the Finnish type due to mutation in the NPHS-1 gene results in massive proteinuria due to structural abnormality in the glomerular slit diaphragm, and is usually refractory to immunosuppressive therapy. Patients eventually require bilateral nephrectomy and renal replacement therapy, with transplantation being the ultimate goal. Post-transplant recurrence of nephrotic syndrome occurs in about 25% of children and is thought to be immune-mediated secondary to antibodies formed against the nephrin protein in renal allograft. Conventional therapy with calcineurin inhibitors (CNI), cyclophosphamide and corticosteroids with or without plasmapheresis often fails to achieve remission resulting in graft loss in 12-16%. There is limited experience with use of rituximab (RTX) in pediatric organ transplant recipients. We report the first case of post-transplant recurrence of nephrotic syndrome in a 4-yr-old child with CNS due to NPHS-1 mutation in whom CNI, corticosteroid and cyclophosphamide therapy was unsuccessful, but who achieved remission after depletion of B cells with RTX, associated with a decrease in the level of anti-nephrin antibodies. The child remains in remission 5 yr following treatment. Our experience suggests that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation in children with CNS.

  6. A contribution to genetic etiology of complex regional pain syndrome type I (algodystropy syndrome) based on quantitative analysis of digitopalmar dermatoglyphics in sixty men.

    PubMed

    Cvjeticanin, Miljenko; Jajić, Zrinka; Jajić, Ivo

    2005-01-01

    The patterns of the ridges of the skin of the fingers and palms were determined in sixty men with complex regional pain syndrome (type I) as a measure of disease prevention. The study included 25 dermatoglyphic traits: number of epidermal ridges on all ten fingers; their sum for five and ten fingers; four traits on both palms, i.e. between a-b, b-c and c-d triradii; atd angles: and their bilateral sum. The data obtained were compared with those recorded in a control group of 200 pairs of imprints of phenotipycally healthy male adults from the Zagreb area. Statistically significant difference from control values were found in 12 dermatoglyphic variables, including an increased sum of ridges on nine fingers (except for left second finger pad), and total sum for five and ten fingers. These findings suggested the polygenic system responsible for development of dermatoglyphics to be identical with some polygenic loci for the onset of algodystrophy syndrome, which might prove useful in disease prevention (e.g., taking fingerprints following a trauma and before rehabilitation), and to facilitate identification of risk groups, and thus the treatment for this longterm and yet obscure syndrome.

  7. Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised.

    PubMed

    Sinibaldi, Lorenzo; Ursini, Gianluca; Castori, Marco

    2015-03-01

    Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers-Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome - JHS/EDS-HT), and significantly contributes to the quality of life of affected individuals. Most published articles dealt with the link between gJHM (or JHS/EDS-HT) and anxiety-related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi-systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS-HT. Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with depression, attention deficit (and hyperactivity) disorder, autism spectrum disorders, and obsessive-compulsive personality disorder were also found. Few papers investigated the relationship with schizophrenia with contrasting results. The mind-body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system. The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS-HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS-HT in clinical practice.

  8. Management of cardiovascular risk in patients with type 2 diabetes mellitus as a component of the cardiometabolic syndrome.

    PubMed

    Ferdinand, Keith C

    2006-01-01

    Heart disease and stroke are the most life-threatening consequences of diabetes mellitus, with mortality rates up to two to four times higher for persons with diabetes vs. those without and accounting for up to 65% of deaths. The cardiometabolic syndrome is a potent indicator of future risk of type 2 diabetes and concomitant increased potential for cardiovascular morbidity and mortality. Pharmacologic treatment is usually necessary to improve blood pressure and lipids, thereby decreasing the risk of cardiovascular disease. The reduction of cardiovascular and renal risk with type 2 diabetes and elevated blood pressure are compelling indications for thiazide diuretics, blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers. Nevertheless, most patients with type 2 diabetes and elevated blood pressure will require two or more agents to lower blood pressure to the recommended goal of <130/80 mm Hg, and combination therapy may be beneficial. In patients with the cardiometabolic syndrome without type 2 diabetes, the present goal is to maintain BP <140/90 mm Hg, although recent data suggest potential decrease in the progression of prehypertension to hypertension with antihypertensive medication. Furthermore, blockers of the renin-angiotensin system may actually prevent newonset diabetes. It is reasonable for patients with type 2 diabetes and cardiovascular disease to achieve an optional low-density lipoprotein cholesterol (LDL-C) goal <70 mg/dL, and statin therapy should be considered regardless of baseline LDL-C level. In patients with the cardiometabolic syndrome without type 2 diabetes and calculated moderately high-risk status (two or more risk factors; 10-year risk, 10%-20%), the present goal for LDL-C is <130 mg/dL, with perhaps a therapeutic option of <100 mg/dL, and in patients with the cardiometabolic syndrome at lower risk, the LDL-C goal remains <160 mg/dL. Multifactorial management must be utilized to

  9. Klüver Bucy syndrome following hypoglycaemic coma in a patient with glycogen storage disease type Ib.

    PubMed

    Boudjemline, Alix Mollet; Isapof, Arnaud; Witas, Jean-Bernard; Petit, François M; Gajdos, Vincent; Labrune, Philippe

    2010-12-01

    Patients with type I glycogen storage disease (GSD) have poor tolerance to fasting, sometimes less than 3 hours during infancy. Even though most patients are able, as they get older, to tolerate a longer fasting period, they are at permanent risk for fast-induced hypoglycaemia, even in adulthood. Klüver Bucy syndrome, is characterized by psychic blindness (inability to recognize familiar objects), hypermetamorphosis (strong tendency to react to visual stimulus), increased oral exploration, placidity, indiscriminate hyper-sexuality and change in dietary habits. In this case report, we describe the development of Klüver Bucy syndrome in a 28-year-old man with type Ib GSD, following prolonged and severe hypoglycaemia triggered by a common respiratory infection.

  10. Chronic pain in a patient with Ehlers-Danlos syndrome (hypermobility type): The role of myofascial trigger point injections.

    PubMed

    Tewari, Saipriya; Madabushi, Rajashree; Agarwal, Anil; Gautam, Sujeet K; Khuba, Sandeep

    2017-01-01

    Chronic widespread musculoskeletal pain is a cardinal symptom in hypermobility type of Ehler Danlos Syndrome (EDS type III). The management of pain in EDS, however, has not been studied in depth. A 30 year old female, known case of EDS, presented to the pain clinic with complaints of severe upper back pain for 6 months. Physical examination of the back revealed two myofascial trigger points over the left rhomboids and the left erector spinae. Local anaesthetic trigger point injections were given at these points, followed by stretching exercises under analgesic cover for the first week. After 1 week the patient reported 60-80% pain relief. This case highlights that we must keep a high index of suspicion for the more treatable causes of pain like myofascial pain syndrome in patients suffering from EDS, and should address it promptly and appropriately in order to maximise patient comfort.

  11. Genetics Home Reference: Waardenburg syndrome

    MedlinePlus

    ... Type I ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (10 links) WAARDENBURG SYNDROME, TYPE 1 WAARDENBURG SYNDROME, TYPE 2A WAARDENBURG SYNDROME, TYPE ... Syndrome Type I Nayak CS, Isaacson G. Worldwide distribution of Waardenburg syndrome. Ann Otol Rhinol Laryngol. 2003 ...

  12. Buccal anomalies, cephalometric analysis and genetic study of two sisters with orofaciodigital syndrome type I.

    PubMed

    Romero, Martín; Franco, Brunella; del Pozo, Jaime Sánchez; Romance, Ana

    2007-11-01

    Orofaciodigital syndromes have many clinical and cephalometric anomalies, including facial irregularities, oral cavity abnormalities, and malformations of fingers and toes. In this case of twin girls, buccal exploration, cephalometric examination, and genetic analysis were performed to diagnose Orofaciodigital I or Orofaciodigital II syndrome. Clinically, the twins had several dental and skeletal irregularities. Genetic analysis revealed a DNA segment abnormality corresponding to exon 3 and presence of nucleotide change, 243C>G, leading to the missense mutation H81Q. This causative mutation associated with the OFD1 gene has not been reported previously. Both patients were diagnosed as having Orofaciodigital I syndrome.

  13. Changes in Risk Variables of Metabolic Syndrome Since Childhood in Pre-Diabetic and Type 2 Diabetic Subjects

    PubMed Central

    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Berenson, Gerald S.

    2008-01-01

    OBJECTIVE—That type 2 diabetes is associated with the metabolic syndrome is known. However, information is lacking regarding the long-term and adverse changes of metabolic syndrome variables in the development of type 2 diabetes from childhood to adulthood. RESEARCH DESIGN AND METHODS—Observations were examined, retrospectively, in a community-based cohort of normoglycemic (n = 1,838), pre-diabetic (n = 90), and type 2 diabetic (n = 60) subjects followed serially for cardiovascular risk factors during childhood (4–11 years), adolescence (12–18 years), and adulthood (19–44 years). RESULTS—Diabetic subjects versus normoglycemic subjects had significantly higher levels of subscapular skinfold, BMI, triglycerides, glucose, insulin, and homeostasis model assessment of insulin resistance and lower levels of HDL cholesterol beginning in childhood and higher levels of mean arterial pressure (MAP) in adolescence and adulthood. In a multivariate model including BMI, MAP, HDL cholesterol, LDL cholesterol, triglycerides, glucose, and insulin, adjusted for age, age2, race, sex, and race × sex interaction, adverse changes in glucose and LDL cholesterol were independently associated with pre-diabetic subjects, whereas adverse changes in BMI, glucose, and HDL cholesterol were associated with diabetic subjects. As young adults, pre-diabetic and diabetic groups displayed a significantly higher prevalence of obesity, hypertension, dyslipidemia, hyperinsulinemia, and metabolic syndrome. CONCLUSIONS—These findings indicate that adverse levels of risk variables of metabolic syndrome, adiposity, and measures of glucose homeostasis accelerating since childhood characterize the early natural history of type 2 diabetes and underscore the importance of early prevention and intervention on risk factors beginning in childhood. PMID:18628566

  14. Fatal Peritoneal Bleeding Following Embolization of a Carotid-Cavernous Fistula in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Usinskiene, Jurgita; Mazighi, Mikael; Bisdorff, Annouk; Houdart, Emmanuel

    2006-12-15

    We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed.

  15. The Relationship between "MECP2" Mutation Type and Health Status and Service Use Trajectories over Time in a Rett Syndrome Population

    ERIC Educational Resources Information Center

    Young, Deidra; Bebbington, Ami; de Klerk, Nick; Bower, Carol; Nagarajan, Lakshmi; Leonard, Helen

    2011-01-01

    This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use…

  16. Multiple strokes and bilateral carotid dissections: a fulminant case of newly diagnosed Ehlers-Danlos syndrome type IV.

    PubMed

    Dohle, C; Baehring, J M

    2012-07-15

    Ehlers-Danlos Syndrome is a rare group of inheritable disorders resulting in abnormal collagen production, leading to skin fragility, joint hypermobility and easy bruising. Six major subtypes have been identified, of which Type IV most often leads to neurovascular complications, may lead to inner organ rupture and overall has the worst prognosis. Early recognition followed by genetic testing is key, since this diagnosis will guide decision making in the management of complications, influence the choice of antiplatelet medications versus anticoagulants and allow for potentially affected family members to be identified, undergo genetic testing and reproductive counseling. We here report the case of a 50 year old woman with a fulminant presentation of Ehlers Danlos Syndrome Type IV, including bilateral carotid and vertebral artery dissection, multiple strokes and liver rupture. Of note, this patient did not have a known history or obvious clinical features of connective tissue disease. Genetic testing confirmed the diagnosis. Review of her family history revealed multiple family members with a history of aortic dissection or aneurysm rupture. This case illustrates that Ehlers Danlos Syndrome Type IV is an important differential diagnosis even in adult patients without a known history of connective tissue disease and no prior complications.

  17. Coexistence of autoimmune polyglandular syndrome type 2 and diabetes insipidus in pregnancy.

    PubMed

    Krysiak, Robert; Samborek, Malgorzata

    2011-11-01

    Autoimmune polyglandular syndromes are rarely diagnosed conditions characterized by the association of at least 2 organ-specific autoimmune disorders. Very few cases of these syndromes have been described during pregnancy. The authors report a case of a patient diagnosed with autoimmune thyroiditis and a history of HELLP (hemolysis, elevated liver enzymes and low platelet) syndrome in a prior pregnancy. After increasing the levothyroxine dose, she developed Addisonian crisis. Normalization of adrenal cortex function resulted in the appearance of diabetes insipidus. This report shows that pregnancy may influence the course of preexisting endocrine disorders and lead to their unmasking. Although the risk of the development of autoimmune polyglandular syndromes during pregnancy is small, they may pose a serious health problem. The possible presence of these clinical entities should be considered in every woman with 1 or more endocrine disturbances.

  18. Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

    PubMed Central

    Tellez-Avila, Felix I; Sanchez-Avila, Francisco; García-Saenz-de-Sicilia, Mauricio; Chavez-Tapia, Norberto C; Franco-Guzman, Ada M; Lopez-Arce, Gustavo; Cerda-Contreras, Eduardo; Uribe, Misael

    2008-01-01

    AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). METHODS: Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P < 0.001), obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION: The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC. PMID:18720537

  19. Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1.

    PubMed Central

    Gantla, S; Bakker, C T; Deocharan, B; Thummala, N R; Zweiner, J; Sinaasappel, M; Roy Chowdhury, J; Bosma, P J; Roy Chowdhury, N

    1998-01-01

    Crigler-Najjar syndrome type 1 (CN-1) is a recessively inherited, potentially lethal disorder characterized by severe unconjugated hyperbilirubinemia resulting from deficiency of the hepatic enzyme bilirubin-UDP-glucuronosyltransferase. In all CN-1 patients studied, structural mutations in one of the five exons of the gene (UGT1A1) encoding the uridinediphosphoglucuronate glucuronosyltransferase (UGT) isoform bilirubin-UGT1 were implicated in the absence or inactivation of the enzyme. We report two patients in whom CN-1 is caused, instead, by mutations in the noncoding intronic region of the UGT1A1 gene. One patient (A) was homozygous for a G-->C mutation at the splice-donor site in the intron, between exon 1 and exon 2. The other patient (B) was heterozygous for an A-->G shift at the splice-acceptor site in intron 3, and in the second allele a premature translation-termination codon in exon 1 was identified. Bilirubin-UGT1 mRNA is difficult to obtain, since it is expressed in the liver only. To determine the effects of these splice-junction mutations, we amplified genomic DNA of the relevant splice junctions. The amplicons were expressed in COS-7 cells, and the expressed mRNAs were analyzed. In both cases, splice-site mutations led to the use of cryptic splice sites, with consequent deletions in the processed mRNA. This is the first report of intronic mutations causing CN-1 and of the determination of the consequences of these mutations on mRNA structure, by ex vivo expression. PMID:9497253

  20. Glucose transporter type 1 deficiency syndrome (Glut1DS): methylxanthines potentiate GLUT1 haploinsufficiency in vitro.

    PubMed

    Ho, Y Y; Yang, H; Klepper, J; Fischbarg, J; Wang, D; De Vivo, D C

    2001-08-01

    Methylxanthines such as caffeine and theophylline are known to inhibit glucose transport. We have studied such inhibition in the glucose transporter type 1 deficiency syndrome (Glut1DS) by erythrocyte glucose transport assays. Data from four patients with individual mutations in the GLUT1 gene are discussed: patient 1 (hemizygosity), 3 (S66F), 15 (368Ins23), and 17 (R333W). Zero-trans influx of (14)C-labeled 3-O-methyl glucose (3-OMG) into erythrocytes of patients is reduced (patient 1, 51%; 3, 45%; 15, 31%; 17, 52%) compared with maternal controls. Inhibition studies on patients 1, 3, 17, and maternal controls show an IC(50) for caffeine of approximately 1.5 mM both in controls (n = 3) and patients (n = 3) at 5 mM 3-OMG concentration. In the same two groups, kinetic studies show that 3 mM caffeine significantly decreases V(max) (p < 0.005), whereas the decrease in K(m) is significant (p < 0.01) only in the three controls and one patient (patient 3). Kinetic data from individual patients permit us to speculate that the interactions between caffeine and Glut1 are influenced by the mutation. Three mM caffeine also inhibits the transport of dehydroascorbic acid (DHA), another substrate for Glut1. The combined effects of caffeine (3 mM) and phenobarbital (10 mM) on glucose transport, as determined in patient 15 and the maternal control, show no additive or synergistic inhibition. These data indicate that caffeine and phenobarbital have similar Glut1 inhibitory properties in these two subjects. Our study suggests that Glut1DS patients may have a reduced safety margin for methylxanthines. Consumption of methylxanthine-containing products may aggravate the neurologic symptoms associated with the Glut1DS.

  1. Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome

    PubMed Central

    Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres

    2013-01-01

    Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging. PMID:24324434

  2. Effects of Dairy Protein and Fat on the Metabolic Syndrome and Type 2 Diabetes

    PubMed Central

    Bjørnshave, Ann; Hermansen, Kjeld

    2014-01-01

    The incidence of the metabolic syndrome (MetS) and type 2 diabetes (T2D) is increasing worldwide. Evidence supports a negative relationship between the consumption of dairy products and risk of MetS and T2D. Dairy proteins are known to have a directly beneficial effect on hypertension, dyslipidemia, and hyperglycemia, but a detailed understanding of the underlying mechanisms is missing. It has been confirmed by observations that the insulinotropic effect of dairy proteins is associated with the amino acid composition; in particular branched-chain amino acids (BCAA) seem to be of vital importance. Dairy protein-derived peptides may also contribute to the insulinotropic effect via dipeptidyl peptidase-4 (DPP-4) inhibitory activity, and may lower the blood pressure (BP). The lipid metabolism may be improved by whey protein (WP), which acts to reduce the postprandial triglyceride (TG) response. The effect of dairy fat is much more controversial because of the potentially harmful effect exerted by saturated fatty acid (SFA) on metabolic health. Recent observations suggest less adverse effects of SFA on metabolic health than previous assumed. However, little is known about dairy lipid fractions belonging to the groups of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and phospholipids (PL). Dairy fat seems to act differently depending on the dairy product and the composition of macronutrients in the meal. Therefore, for a better understanding of the mechanisms behind the dairy protein and fat effect on MetS, we suggest that more human studies should be carried out to clarify the interactions of dairy protein and fat with macronutrients in the meal and other dairy components, such as micronutrients and microorganisms from fermented products. PMID:25396403

  3. Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus

    PubMed Central

    Arab, Juan P; Claro, Juan C; Arancibia, Juan P; Contreras, Jorge; Gómez, Fernando; Muñoz, Cristian; Nazal, Leyla; Roessler, Eric; Wolff, Rodrigo; Arrese, Marco; Benítez, Carlos

    2016-01-01

    AIM To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension. METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded. RESULTS Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described. CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1. PMID:27660674

  4. Corrections of diverse forms of lower limb deformities in patients with mucopolysaccharidosis type IVA (Morquio syndrome)

    PubMed Central

    Al Kaissi, Ali; Kenis, Vladimir; Melchenko, Eugeniy; Ghachem, Maher Ben; Csepan, Robert; Grill, Franz; Ganger, Rudolf

    2016-01-01

    Background: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS) type IV (Morquio's syndrome). However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. Materials and Methods: Ten patients (seven children and three adults) with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. Results: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N-acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. Conclusion: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme replacement therapy

  5. Sanfilippo syndrome type B: cDNA and gene encoding human {alpha}-N-acetylglucosaminidase

    SciTech Connect

    Zhao, H.G.; Lopez, R.; Rennecker, J.

    1994-09-01

    Deficiency of the lysosomal enzyme {alpha}-N-acetlyglucosaminidase underlies the type B Sanfilippo syndrome (MPS III B), a mucopolysaccharide storage disease with profound neurologic deterioration. We are acquiring tools to study the molecular basis of the disorder. The enzyme was purified from bovine testis; after ConA-, DEAE- and phenyl-Sepharose chromatography, it was subjected to SDS-PAGE without preheating. Of two bands of activity detected on the gel, 170 kDa and 87 kDa, the larger one, which coincided with a well-defined Coomassie blue band, was selected for sequence analysis. Degenerate 17-base oligonucleotides, corresponding to the ends of an internal 23 amino acid sequence, were used for RT-PCR of RNA from human fibroblasts. A 41-mer was synthesized from the sequence of the RT-PCR product and used to screen a human testis cDNA library. A number of cDNA inserts were isolated, all lacking the 5{prime} end and none longer than 1.7 kb. An additional 300 bp segment has been obtained by RACE. The cDNA sequence accounts for 9 of 11 peptides, allowing for species difference. Northern analysis of fibroblast RNA with a 1.5 kb cDNA probe showed the presence of a 3 kb mRNA; marked deficiency of this mRNA in two MPS III B fibroblast lines confirmed the authenticity of the cloned cDNA. While no homologous amino acid sequence has been found in a search of GenBank, the nucleotide sequence (interrupted by 4 introns) is present in a flanking region upstream of an unrelated gene on chromosome 17q11-21 (human 17{beta}-hydroxysteroid dehydrogenase). This must therefore be the chromosomal locus of the {alpha}-N-acetylglucosaminidase gene and of MPS III B.

  6. Autoantibodies against muscarinic type 3 receptor in Sjögren's syndrome inhibit aquaporin 5 trafficking.

    PubMed

    Lee, Byung Ha; Gauna, Adrienne E; Perez, Geidys; Park, Yun-jong; Pauley, Kaleb M; Kawai, Toshihisa; Cha, Seunghee

    2013-01-01

    Sjögren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (α-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal α-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS.

  7. PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1

    PubMed Central

    Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming

    2010-01-01

    Purpose To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Methods Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Results Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Conclusions Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before. PMID:20664692

  8. Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients.

    PubMed

    Prattichizzo, Clelia; Macca, Marina; Novelli, Valeria; Giorgio, Giovanna; Barra, Adriano; Franco, Brunella

    2008-10-01

    Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81%). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60% of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome.

  9. Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI): report on 23 patients and review of the literature.

    PubMed

    Al-Hussain, Hailah; Zeisberger, Steffen M; Huber, Peter R; Giunta, Cecilia; Steinmann, Beat

    2004-01-01

    The brittle cornea syndrome (BCS) is a generalized connective tissue disorder characterized by corneal rupture following only minor trauma, keratoconus or keratoglobus, blue sclerae, hyperelasticity of the skin without excessive fragility, and hypermobility of the joints. It is inherited as an autosomal recessive trait but the underlying genetic defect remains undetermined. We present 23 patients (11 male) from 13 nuclear families followed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, aged 3-28 years at last follow-up. A total of 28 events of corneal rupture were noted in 17 patients (eight male), among whom nine had had bilateral ruptures, and eight had had unilateral ruptures (four of the right cornea), while two had experienced re-rupture 2 and 4 years, respectively, after surgery; six patients (aged 3-21 years) had had no ruptures. We describe the natural history of our cases and discuss them together with those others reported in the literature. Because of similarities between the BCS and the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VI), both disorders tend to have been confounded. Here, we show that all of our BCS patients tested in this regard had biochemical findings reflective of normal activity of lysyl hydroxylase, characteristically deficient in EDS VI, such as normal urinary total pyridinoline ratios and/or normal electrophoretic migration of collagen chains produced by dermal fibroblasts. The BCS is, therefore, an entity distinct from the kyphoscoliotic type of EDS, which has a much poorer prognosis.

  10. The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome.

    PubMed

    Sofer, S; Schweiger, A; Blumkin, L; Yahalom, G; Anikster, Y; Lev, D; Ben-Zeev, B; Lerman-Sagie, T; Hassin-Baer, S

    2015-04-01

    Costeff syndrome is a rare genetic neuro-ophthalmological syndrome consisting of early-onset bilateral optic atrophy along with a progressive complex motor disorder with elevated levels of urinary 3-methylglutaconic acid and 3-methylglutaric acid. While borderline to mild cognitive deficits have been considered to be common in patients with this syndrome, a comprehensive cognitive assessment has never been performed. The aim of the current study was to explore the cognitive profile associated with Costeff syndrome. Sixteen adult patients diagnosed with Costeff syndrome were administered a neuropsychological test battery that was composed of standardized verbal tests adapted for the blind. General intelligence ranged from average to borderline, with a group mean consistent with intact general cognitive functioning (VIQmean  = 85, z = -1) in the low-average range of the general population. The auditory immediate and delayed memory indexes were in the average range and were significantly higher than the general cognitive functioning, whereas the working memory index was significantly lower than the general cognitive functioning. Adult patients with Costeff syndrome have intact global cognition and learning abilities and strong auditory memory performance. © 2015 Wiley Periodicals, Inc.

  11. Metabolic syndrome components and prevalence of cardiovascular disease among type 2 diabetic patients in Malaysia.

    PubMed

    Tan, Mun Chieng; Wong, Teck Wee; Ng, Ooi Chuan; Joseph, Anthony; Hejar, Abdul Rahman

    2014-01-01

    Metabolic syndrome (MetS) is common among patients with type 2 diabetes mellitus (T2DM) and increases the risk of cardiovascular disease (CVD) and all-cause mortality. The objective of this study was to investigate the association between the components of MetS and the prevalence of CVD among patients with T2DM. We studied 313 patients aged > or = 30 years diagnosed with T2DM at two tertiary care hospitals. Patients were recruited by systematic random sampling. Clinical data was obtained using an interviewer-administered structured questionnaire and from a review of their medical records. MetS was diagnosed using NCEP ATP III, WHO, IDF and the new Harmonized definitions. Specific MetS components such as BMI, waist circumference, waist-to-hip ratio, hypertension, HDL-C and triglyceride levels were evaluated to determine if they had an association with CVD. Thirty-six point one percent of the subjects had CVD. The mean age of the subjects was 55.7 +/- 9.2 years and the mean duration of having diabetes was 10.1 +/- 8.1 years. The overall prevalences of MetS (> or = 3 of 5 components) (95% CI) were 96.1% (94.0-98.3), 95.8% (93.6-98.1), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) using NCEP ATP III, WHO, IDF and Harmonized definitions, respectively. Patients with MetS had a higher prevalence of CVD using NCEP ATP III (98.2% vs 93.5%), WHO (98.2% vs 93.0%), IDF (87.6% vs 82.0%) and Harmonized criteria (98.2% vs 96.0%). The greater the number of MetS components, the greater the chance of having CVD using three definitions for diagnosing MetS: WHO, IDF and Harmonized (p < 0.05). MetS and the combination of the individual components of MetS were significantly associated with CVD among type 2 diabetic patients in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.

  12. Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome

    PubMed Central

    2013-01-01

    Background Whereas mutations affecting the helical domain of type I procollagen classically cause Osteogenesis Imperfecta (OI), helical mutations near the amino (N)-proteinase cleavage site have been suggested to result in a mixed OI/Ehlers-Danlos syndrome (EDS)-phenotype. Methods We performed biochemical and molecular analysis of type I (pro-) collagen in a cohort of seven patients referred with a clinical diagnosis of EDS and showing only subtle signs of OI. Transmission electron microscopy of the dermis was available for one patient. Results All of these patients harboured a COL1A1 / COL1A2 mutation residing within the most N-terminal part of the type I collagen helix. These mutations affect the rate of type I collagen N-propeptide cleavage and disturb normal collagen fibrillogenesis. Importantly, patients with this type of mutation do not show a typical OI phenotype but mainly present as EDS patients displaying severe joint hyperlaxity, soft and hyperextensible skin, abnormal wound healing, easy bruising, and sometimes signs of arterial fragility. In addition, they show subtle signs of OI including blue sclerae, relatively short stature and osteopenia or fractures. Conclusion Recognition of this distinct phenotype is important for accurate genetic counselling, clinical management and surveillance, particularly in relation to the potential risk for vascular rupture associated with these mutations. Because these patients present clinical overlap with other EDS subtypes, biochemical collagen analysis is necessary to establish the correct diagnosis. PMID:23692737

  13. Executive functioning in children with Asperger syndrome, ADHD-combined type, ADHD-predominately inattentive type, and controls.

    PubMed

    Semrud-Clikeman, Margaret; Walkowiak, Jenifer; Wilkinson, Alison; Butcher, Brianne

    2010-08-01

    The purpose of the study was to evaluate neuropsychological and behavioral rating measures of executive functions (EF) in children with two subtypes of ADHD, Asperger syndrome (AS), and controls. Relative to the control group, the clinical groups experienced more difficulty in EF. The AS group showed the most difficulty in emotional control, behavioral regulation, fluid reasoning, and planning compared to the ADHD groups. Number of symptoms of ADHD or AS was found to be significantly related to ratings of difficulty with behavior regulation, metacognition, and general behavioral regulation across the sample. These findings indicate that children with AS or ADHD may have a differing EF profile and thus, may respond differentially to interventions.

  14. Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome.

    PubMed

    Lohan, S; Spielmann, M; Doelken, S C; Flöttmann, R; Muhammad, F; Baig, S M; Wajid, M; Hülsemann, W; Habenicht, R; Kjaer, K W; Patil, S J; Girisha, K M; Abarca-Barriga, H H; Mundlos, S; Klopocki, E

    2014-10-01

    Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome.

  15. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse.

    PubMed Central

    Foy, C; Newton, V; Wellesley, D; Harris, R; Read, A P

    1990-01-01

    We have demonstrated close linkage between the locus for the autosomal dominant Waardenburg syndrome type I and the placental alkaline phosphatase locus on chromosome 2q37. In five families the peak lod score was 4.76 at a recombination fraction of .023. In the mouse the Splotch locus maps to near the homologous position. Splotch mice have white spotting and hearing defects, suggesting that Splotch may be the murine homologue of Waardenburg syndrome type I. PMID:2339698

  16. Diet-Induced Swine Model with Obesity/Leptin Resistance for the Study of Metabolic Syndrome and Type 2 Diabetes

    PubMed Central

    Torres-Rovira, L.; Astiz, S.; Caro, A.; Lopez-Bote, C.; Ovilo, C.; Pallares, P.; Perez-Solana, M. L.; Sanchez-Sanchez, R.; Gonzalez-Bulnes, A.

    2012-01-01

    The objective of the present study was to determine the suitability of a swine breed with leptin resistance and predisposition to obesity (the Iberian pig) as model for studies on metabolic syndrome and type 2 diabetes. Thus, six Iberian sows had ad libitum access to food enriched with saturated fat (SFAD group; food consumption was estimated to be 4.5 kg/animal/day) whilst four females acted as controls and were fed with 2 kg/animal/day of a commercial maintenance diet. After three months of differential feeding, SFAD animals developed central obesity, dyslipidemia, insulin resistance and impaired glucose tolerance, and elevated blood pressure; the five parameters associated with the metabolic syndrome. Thus, the current study characterizes the Iberian pig as a robust, amenable, and reliable translational model for studies on nutrition-associated diseases. PMID:22629144

  17. Dermal ultrastructure in low Beighton score members of 17 families with hypermobile-type Ehlers-Danlos syndrome.

    PubMed

    Hermanns-Lê, Trinh; Reginster, Marie-Annick; Piérard-Franchimont, Claudine; Delvenne, Philippe; Piérard, Gérald E; Manicourt, Daniel

    2012-01-01

    The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH.

  18. [Type A Wolff-Parkinson-White syndrome associated with left bundle-branch block. Electrocardiographic, vectorcardiographic, and endocavitary electrophysiological study].

    PubMed

    Baudouy, M; Molina, B; Varenne, A; Guiran, J B

    1976-05-01

    The rate association of a "type A" W.P.W. syndrome with a left bundle branch block gives a characteristic electrocardiographic picture:--the left bundle branch block is partially masked, the delay in the basial region of the left ventricle being in part cancelled by pre-excitation--the features of the W.P.W. syndrome are also modified, since the ventricular axis is corrected by the left bundle branch block. The electrocardiographic tracings taken during the various tachycardias and during treatment for arrhythmia, together with the intra-cavitary recordings allow a precise diagnosis to be made. In this case, vectocardiography was particularly useful as it gave a clear demonstration of the median delay of the ventricular loop, the only pathognomic feature of left bundle branch block, during a period when the left bundle of Kent was functioning.

  19. Lunch energy density and the metabolic syndrome in patients with type 2 diabetes mellitus.

    PubMed

    Menegotto, Giovana; Moraes Silva, Flávia; de Azevedo, Mirela Jobim; de Almeida, Jussara Carnevale

    2013-11-14

    The aim of the present study was to investigate the possible associations between dietary energy density (ED) and the metabolic syndrome (MetS) in patients with type 2 diabetes. In the present case-control study, the dietary ED of 125 patients with type 2 diabetes (seventy-eight with (cases) the MetS and forty-seven without (controls) the MetS; mean age 62·0 (SD 9·4) years, mean diabetes duration 12·5 (SD 8·4) years and mean glycated Hb 7·2 (SD 1·3) %) was assessed by weighed diet records. The MetS was defined according to the 2009 Joint Interim Statement and ED by the amount of energy (kJ) in a given weight of food. Data are expressed as means (standard deviations) or medians (interquartile ranges). Patients with the MetS reported lower intakes of total energy and fibre, and a higher total food amount than the controls; the total ED did not differ, but the cases had a higher ED at lunch (mean 6·3 (SD 1·3) v. 5·9 (SD 0·8) kJ/g; P= 0·017). In this meal, patients with the MetS had lower intakes of beans (median 0·7 (interquartile range 0·4-1·1) v. 1·1 (interquartile range 0·6-1·6) g/kg; P= 0·020), vegetables (median 1·2 (interquartile range 0·6-1·7) v. 1·4 (interquartile range 1·0-2·0) g/kg; P= 0·046) and total meat (median 1·3 (interquartile range 1·0-1·6) v. 1·4 (interquartile range 1·2-1·8) g/kg; P= 0·034) than patients without the MetS. The associations between lunch ED (kJ/g) and food groups (g/kg) were confirmed for vegetables (r - 0·584; P< 0·001), fruits (r - 0·233; P= 0·070), beans (r - 0·189; P= 0·037) and oils (r 0·323; P< 0·001). In a multivariate logistic regression model, a high lunch ED was associated with the MetS (OR 6·89, 95 % CI 1·35, 35·15; P =0·020) after adjusting for confounders. In conclusion, a high ED at lunch increased the odds of the presence of the MetS in patients with type 2 diabetes. Beans and vegetables may be the major contributors to this association and their consumption might be

  20. Oromandibular-limb Hypogenesis Syndrome Type II C: A Rare Case

    PubMed Central

    Lorina Castelino, Renita; Ram Shetty, Shishir; Babu G, Subhas; Arvind Rao H T, Kumuda

    2010-01-01

    The oromandibular-limb hypogenesis syndrome comprises a group of anomalies which simultaneously affect the mandible, tongue, and maxilla with or without reductive limb anomalies. It is characterized by failure of development of the intraoral region and distal extremities. Multiple and variable deformities of the mandible, maxilla and tongue may occur in combination with a variety of limb defects. The wide range of presentation and combination of anomalies make classification difficult. They usually feature primarily in sporadic case reports because of their low incidence. The genetic origin of this syndrome is uncertain. It is congenital and there seems to be no sex predilection. The key radiographic features are retruded mandible, impacted teeth and malformed phalanges. When compared to available literature, frequently reported features like hypodontia, hypoglossia, microstomia, protruded maxilla and limb anomalies were present in our case. The case presented here is one of the rarest subtypes of this rare syndrome. PMID:23346341

  1. Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome

    PubMed Central

    Zhang, Yun-Bo; Chi, Mei-Hua

    2016-01-01

    Purpose Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). Materials and Methods We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. Results The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. Conclusion Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma. PMID:26996569

  2. Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women

    PubMed Central

    Dragsbæk, Katrine; Neergaard, Jesper S.; Laursen, Janne M.; Hansen, Henrik B.; Christiansen, Claus; Beck-Nielsen, Henning; Karsdal, Morten A.; Brix, Susanne; Henriksen, Kim

    2016-01-01

    Abstract The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD) in elderly Caucasian women. We further investigated if stratification of individuals not defined with MetS would add predictive power in defining future disease prevalence of individuals with MetS. The Prospective Epidemiological Risk Factor Study, a community-based cohort study, followed 3905 Danish women since 2000 (age: 70.1 ± 6.5) with no previous diagnosis of T2DM or CVD, holding all measurements used for MetS definition; central obesity, hypertension, hyperlipidemia, and hyperglycemia combined with register-based follow-up information. Elderly women with defined MetS presented a 6.3-fold increased risk of T2DM (95% confidence interval: [3.74–10.50]) and 1.7-fold increased risk of CVD (1.44–2.05) compared to women with no MetS risk factors. Subdividing the control group without defined MetS revealed that both centrally obese controls and controls holding other MetS risk factors also had increased risk of T2DM (hazard ratio (HR) = 2.21 [1.25–3.93] and HR = 1.75 [1.04–2.96]) and CVD (HR = 1.51 [1.25–1.83] and HR = 1.36 [1.15–1.60]) when compared to controls with no MetS risk factors. MetS in elderly Caucasian women increased risk of future T2DM and CVD. While not defined with MetS, women holding only some risk factors for MetS were also at increased risk of T2DM or CVD compared to women with no MetS risk factors. PMID:27603394

  3. Protective Effects of the Mediterranean Diet on Type 2 Diabetes and Metabolic Syndrome.

    PubMed

    Salas-Salvadó, Jordi; Guasch-Ferré, Marta; Lee, Chih-Hao; Estruch, Ramón; Clish, Clary B; Ros, Emilio

    2016-03-09

    Several studies provide evidence supporting a beneficial effect from the traditional Mediterranean diet (MedDiet) on the risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). This review summarizes the current scientific evidence from epidemiologic studies and clinical trials on the relation between the MedDiet and T2DM and MetS and the possible mechanisms underlying the reported associations. A recent meta-analysis of prospective cohort studies showed that greater adherence to the MedDiet was associated with a significant reduction in the risk of diabetes. The MedDiet has also been found to be beneficial in the prevention of gestational diabetes. Four large prospective studies have observed inverse associations between the MedDiet and MetS or its components. Few randomized controlled trials (RCTs) have evaluated the effect of the MedDiet on T2DM and MetS. Results from the landmark PREvención con DIeta MEDiterránea (PREDIMED) nutrition intervention trial showed that participants assigned to the MedDiet had a significant 30% reduction in the risk of T2DM and that it also promoted the reversion of MetS and its components, hyperglycemia and central obesity. In addition, 5 RCTs showed the beneficial effects of the MedDiet compared with other dietary patterns on glycemic control in patients with T2DM. A recent meta-analysis of RCTs revealed that, compared with a variety of control diets, the MedDiet was associated with beneficial effects on all MetS components. Bioactive components of the MedDiet synergize to affect various metabolic pathways, leading to a reduced cardiometabolic disease risk. The abundance of healthy, nutrient-dense foods that make up the plant-based MedDiet predicts its bioactivity and potential to beneficially influence metabolic pathways that lead to MetS and T2DM, as well as other chronic conditions. Abundant epidemiologic and clinical trial evidence supports the role of the MedDiet on the prevention and management of T2DM and

  4. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    PubMed

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted.

  5. The effects of neuromuscular taping on gait walking strategy in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type

    PubMed Central

    Camerota, Filippo; Galli, Manuela; Celletti, Claudia; Ancillao, Andrea; Blow, David; Albertini, Giorgio

    2015-01-01

    Objective: In this case study, biomechanical alterations induced by neuromuscular taping (NMT) were quantified, during walking, in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT). Methods: A female JHS/EDS-HT patient underwent NMT applications over the low back spine and bilaterally to the knee. Quantitative gait analyses were collected before the NMT application and at the end of the treatment (2 weeks after the first application of NMT). Results: At the end of treatment following the NMT application, left step length showed improvements in cadence and velocity, the left knee showed a reduction in its flexed position at initial contact, and the right ankle joint improved its position at initial contact and in the swing phase. Improvements were also found in kinetics, in terms of the ankle moment and power. Conclusions: Results show that NMT seems to be a promising low-cost intervention for improving gait strategy in patients with JHS/EDS-HT. Further investigations are needed to assess the effects of this treatment intervention on pathological symptoms. PMID:25649985

  6. Management of pain and fatigue in the joint hypermobility syndrome (a.k.a. Ehlers-Danlos syndrome, hypermobility type): principles and proposal for a multidisciplinary approach.

    PubMed

    Castori, Marco; Morlino, Silvia; Celletti, Claudia; Celli, Mauro; Morrone, Aldo; Colombi, Marina; Camerota, Filippo; Grammatico, Paola

    2012-08-01

    Joint hypermobility syndrome (JHS), or Ehlers-Danlos syndrome (EDS) hypermobility type (EDS-HT), is a underdiagnosed heritable connective tissue disorder characterized by generalized joint hypermobility and a wide range of visceral, pelvic, neurologic, and cognitive dysfunctions. Deterioration of quality of life is mainly associated with pain and fatigue. Except for the recognized effectiveness of physiotherapy for some musculoskeletal features, there are no standardized guidelines for the assessment and treatment of pain and fatigue. In this work, a practical classification of pain presentations and factors contributing in generating painful sensations in JHS/EDS-HT is proposed. Pain can be topographically classified in articular limb (acute/subacute and chronic), muscular limb (myofascial and fibromyalgia), neuropathic limb, back/neck, abdominal and pelvic pain, and headache. For selected forms of pain, specific predisposing characteristics are outlined. Fatigue appears as the result of multiple factors, including muscle weakness, respiratory insufficiency, unrefreshing sleep, dysautonomia, intestinal malabsorption, reactive depression/anxiety, and excessive use of analgesics. A set of lifestyle recommendations to instruct patients as well as specific investigations aimed at characterizing pain and fatigue are identified. Available treatment options are discussed in the set of a structured multidisciplinary approach based on reliable outcome tools.

  7. A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome.

    PubMed

    Balci, S; Altugan, F S; Alehan, D; Aypar, E; Baltaci, V

    2009-01-01

    A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome: We report a prenatally sonographically diagnosed conotruncal and urogenital anomaly. Postnatally, the patient presented with seizures, hypocalcemia, hypoparathyroidism and thymic aplasia and diagnosed as DiGeorge syndrome. Echocardiography showed malalignment VSD, supravalvular pulmonary stenosis and overriding aorta. Chromosome and FISH studies showed the association of mosaic type trisomy 21 and 22q11.2 microdeletion. The present patient is the second case of mosaic type of Down syndrome associated with 22q11.2 microdeletion. In addition the patient also had clinical and laboratory features of DiGeorge syndrome.

  8. Founder mutation R245H of Sanfilippo syndrome type A in the Cayman Islands.

    PubMed

    Rady, Peter L; Surendran, Sankar; Vu, Ahn T; Hawkins, Judy C; Michals-Matalon, Kimberlee; Tyring, Stephan K; Merren, Joy; Kumar, Alla K; Matalon, Reuben

    2002-01-01

    Sanfilippo A syndrome is an autosomal recessive lysosomal storage disease. This disease was reported in the Cayman Islands population with carrier frequency of 1/7 to 1/10 in the West Bay district of Grand Cayman. The carrier testing of Sanfilippo A disease for families at risk was carried out using the thermal characteristics of sulfamidase activity. In the present study, a search for mutations in the sulfamidase gene in an index family was performed. In addition, 77 individuals, relatives of children with Sanfilippo A syndrome, were also studied by single-strand conformation polymorphism (SSCP), restriction fragment-length polymorphism (RFLP) analyses, and sequencing. A single mutation, G746A (R245H), was found in the family, with the patient being homozygous and both parents and 1 of the 3 siblings being carriers. Among the 77 family members of the patient with Sanfilippo syndrome, the same mutation was found among carriers of the disease. The finding of a single mutation supports the idea of a founder effect, which facilitates accurate carrier identification of Sanfilippo A syndrome in the population of Cayman Islands.

  9. Binge eating disorder and night eating syndrome in adults with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the prevalence of binge eating disorder (BED) and night eating syndrome (NES) among applicants to the Look AHEAD (Action for Health in Diabetes) study. The Eating Disorders Examination-Questionnaire (EDE-Q) and the Night Eating Questionnaire (NEQ) were used to screen patients. Phone int...

  10. Clonal Rett Syndrome cell lines to test compounds for activation of wild-type MeCP2 expression.

    PubMed

    Yu, Dongbo; Sakurai, Fuminori; Corey, David R

    2011-09-15

    Rett Syndrome is an X-linked progressive neurological disorder caused by inactivation of one allele of the MECP2 gene. There are no curative treatments, and activation of wild-type MECP2 expression is one strategy for stabilizing or reversing the disease. We isolated fibroblast clones that express exclusively either the wild-type or a 32-bp-deletion mutant form of MECP2. We developed a sensitive assay for measuring wild-type MECP2 mRNA levels and tested small molecule epigenetic activators for their ability to activate gene expression. Although our pilot screen did not identify activators of MECP2 expression, it established the value of using clonal cells and defined challenges that must be overcome.

  11. Nonuremic Indication for Peritoneal Dialysis for Refractory Heart Failure in Cardiorenal Syndrome Type II: Review and Perspective

    PubMed Central

    Nakayama, Masaaki

    2013-01-01

    Cardiorenal syndrome (CRS) type II is a serious condition in which chronic cardiac abnormalities cause worsening kidney function, leading to permanent chronic kidney damage. Management of CRS type II coupled with diuretic-resistant congestive heart failure (CHF) has been an issue of dispute. However, since the early 1990s, reports indicating the clinical usefulness of peritoneal dialysis (PD) as maintenance therapy for intractable CHF in this population have been accumulating. The present manuscript reviews the mechanisms by which kidney dysfunction develops within CHF, and then examines recent experiences of PD as chronic supportive therapy for intractable CRS type II, reviews the contributing mechanisms, and discusses the rationale for using PD as a new therapeutic approach in the nonuremic setting of CHF. PMID:23349193

  12. [EHLERS-DANLOS SYNDROME OF THE HYPERMOBILE TYPE: A MULTISYSTEMIC DISORDER. CONTRIBUTION OF SKIN ULTRASTRUCTURE TO INDIVIDUAL MANAGEMENT].

    PubMed

    Hermanns-Lê, T; Piérard, G E; Piérard-Franchimont, C

    2015-01-01

    Ehlers-Danlos syndrome (EDS) represents a heterogeneous group of disorders of the connective tissue structure. Currently, several types are distinguished following a limited set of clinical signs and genetic mutations. However, there is a lack of specificity of most recognized genetic alterations with the current clinical typing. In addition, the criteria from dermatopathology, ultrastructure and biomechanics are not considered. In addition, the established EDS frontiers are hazardous because a series of anatomo-clinical signs are not considered in the classical EDS concept. The hypermobile type EDS represents an example of the diagnostic uncertainties. It results that guidelines based on evidence-based medicine cannot be established. Only an individual management can be offered to the concerned patients.

  13. A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus–syndrome X complex

    PubMed Central

    Koeslag, Johan H; Saunders, Peter T; Terblanche, Elmarie

    2003-01-01

    Blood glucose concentrations are unaffected by exercise despite very high rates of glucose flux. The plasma ionised calcium levels are even more tightly controlled after meals and during lactation. This implies ‘integral control’. However, pairs of integral counterregulatory controllers (e.g. insulin and glucagon, or calcitonin and parathyroid hormone) cannot operate on the same controlled variable, unless there is some form of mutual inhibition. Flip-flop functional coupling between pancreatic α- and β-cells via gap junctions may provide such a mechanism. Secretion of a common inhibitory chromogranin by the parathyroids and the thyroidal C-cells provides another. Here we describe how the insulin:glucagon flip-flop controller can be complemented by growth hormone, despite both being integral controllers. Homeostatic conflict is prevented by somatostatin-28 secretion from both the hypothalamus and the pancreatic islets. Our synthesis of the information pertaining to the glucose homeostat that has accumulated in the literature predicts that disruption of the flip-flop mechanism by the accumulation of amyloid in the pancreatic islets in type 2 diabetes mellitus will lead to hyperglucagonaemia, hyperinsulinaemia, insulin resistance, glucose intolerance and impaired insulin responsiveness to elevated blood glucose levels. It explains syndrome X (or metabolic syndrome) as incipient type 2 diabetes in which the glucose control system, while impaired, can still maintain blood glucose at the desired level. It also explains why it is characterised by high plasma insulin levels and low plasma growth hormone levels, despite normoglycaemia, and how this leads to central obesity, dyslipidaemia and cardiovascular disease in both syndrome X and type 2 diabetes. PMID:12717005

  14. A newly described bovine type 2 scurs syndrome segregates with a frame-shift mutation in TWIST1.

    PubMed

    Capitan, Aurélien; Grohs, Cécile; Weiss, Bernard; Rossignol, Marie-Noëlle; Reversé, Patrick; Eggen, André

    2011-01-01

    The developmental pathways involved in horn development are complex and still poorly understood. Here we report the description of a new dominant inherited syndrome in the bovine Charolais breed that we have named type 2 scurs. Clinical examination revealed that, despite a strong phenotypic variability, all affected individuals show both horn abnormalities similar to classical scurs phenotype and skull interfrontal suture synostosis. Based on a genome-wide linkage analysis using Illumina BovineSNP50 BeadChip genotyping data from 57 half-sib and full-sib progeny, this locus was mapped to a 1.7 Mb interval on bovine chromosome 4. Within this region, the TWIST1 gene encoding a transcription factor was considered as a strong candidate gene since its haploinsufficiency is responsible for the human Saethre-Chotzen syndrome, characterized by skull coronal suture synostosis. Sequencing of the TWIST1 gene identified a c.148_157dup (p.A56RfsX87) frame-shift mutation predicted to completely inactivate this gene. Genotyping 17 scurred and 20 horned founders of our pedigree as well as 48 unrelated horned controls revealed a perfect association between this mutation and the type 2 scurs phenotype. Subsequent genotyping of 32 individuals born from heterozygous parents showed that homozygous mutated progeny are completely absent, which is consistent with the embryonic lethality reported in Drosophila and mouse suffering from TWIST1 complete insufficiency. Finally, data from previous studies on model species and a fine description of type 2 scurs symptoms allowed us to propose different mechanisms to explain the features of this syndrome. In conclusion, this first report on the identification of a potential causal mutation affecting horn development in cattle offers a unique opportunity to better understand horn ontogenesis.

  15. Uric acid concentration in subjects at risk of type 2 diabetes mellitus: relationship to components of the metabolic syndrome.

    PubMed

    Costa, A; Igualá, I; Bedini, J; Quintó, L; Conget, I

    2002-03-01

    High uric acid concentration is a common finding in subjects with risk factors for cardiovascular disease (CVD), including some characteristics of the metabolic syndrome. However, its exact role in this setting and in the progression to type 2 diabetes mellitus (DM) is not well understood and could be affected by confounding factors such as hypertriglyceridemia. Our study aimed to establish the relationship between uric acid (avoiding the interference of high triglyceride levels), insulin sensitivity, and components of the metabolic syndrome in a group of subjects at high risk of developing DM. Among 201 subjects included in the study, 111 (55.2%) showed an abnormal oral glucose tolerance and uric acid levels higher than those measured in subjects with normal glucose tolerance. Body mass index (BMI), triglycerides, diastolic blood pressure (DBP), and 2-hour glycemia in the oral glucose tolerance test (OGTT) contributed independently to uric acid concentration (R2 =.59). However, uric acid did not affect either insulin sensitivity or glucose tolerance. The recovery tests revealed that a triglyceride concentration > or = 3 mmol/L interfered with the measurement of uric acid level when a colorimetric method was used, but not when a dry-chemistry method was used. In conclusion, uric acid concentration is higher in subjects at high risk of DM with abnormal glucose tolerance and is independently determined by various components of the metabolic syndrome.

  16. Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome.

    PubMed

    Hung, Pi-Lien; Huang, Li-Tung; Kwan, Shang-Yeong; Chang, Kai-Ping; Chen, Hsin-Hung; Lee, Yi-Yen; Fan, Hueng-Chuen; Chen, Chien

    2017-03-08

    We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic-clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video-EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack. The ictal vomiting ceased following management with oxcarbazepine, high-dose phenobarbital, and a ketogenic diet. The unique seizure type and rare ictal EEG findings are the first reported in a child with chromosome 22q11.2 deletion syndrome. This case highlights that ictus emeticus without detectable epileptic discharge on EEG is one potential epileptic presentation in this genetic syndrome. [Published with video sequences on www.epilepticdisorders.com].

  17. Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

    PubMed

    Sánchez-Corona, J; Flores-Martínez, S E; Machorro-Lazo, M V; Galaviz-Hernández, C; Morán-Moguel, M C; Perea, F J; Mújica-López, K I; Vargas-Ancona, L; Laviada-Molina, H A; Fernández, V; Pardío, J; Arroyo, P; Barrera, H; Hanson, R L

    2004-01-01

    The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

  18. Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

    PubMed Central

    Castori, Marco

    2012-01-01

    Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners' awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists. PMID:23227356

  19. A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4

    PubMed Central

    Wang, Xiong; Zhu, Yaowu; Shen, Na; Peng, Jing; Wang, Chunyu; Liu, Haiyi; Lu, Yanjun

    2017-01-01

    Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A–C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation. PMID:28128317

  20. The first scintigraphic detection of tumor necrosis factor-alpha in patients with complex regional pain syndrome type 1.

    PubMed

    Bernateck, Michael; Karst, Matthias; Gratz, Klaus F; Meyer, Geerd J; Fischer, Michael J; Knapp, Wolfram H; Koppert, Wolfgang; Brunkhorst, Thomas

    2010-01-01

    Tumor necrosis factor (TNF)-alpha has been identified as a pathogenic factor in many immunologically based diseases and complex regional pain syndrome (CRPS). In this case series, we used radiolabeled technetium anti-TNF-alpha antibody to scintigraphically image TNF-alpha in 3 patients with type 1 CRPS. The results show that TNF-alpha was localized only in affected hands of patients with early-stage CRPS. No uptake was seen in clinically unaffected hands and late-stage CRPS. Our findings support the growing evidence for neuroimmune disturbance in patients with CRPS and may have important further implications for specific anticytokine treatment in patients with CRPS.

  1. Unilateral laparoscopic adrenalectomy followed by contralateral retroperitoneoscopic partial adrenalectomy in a patient with multiple endocrine neoplasia type 2a syndrome.

    PubMed

    Mugiya, S; Suzuki, K; Saisu, K; Fujita, K

    1999-03-01

    We report the first patient who had bilateral pheochromocytoma associated with multiple endocrine neoplasia type 2a syndrome (MEN 2a) and underwent unilateral laparoscopic adrenalectomy followed by contralateral retroperitoneoscopic partial adrenalectomy 2 years later. The postoperative course was uneventful both times, and the patient was cured of hypertension without any need for steroid replacement. Endoscopic partial adrenalectomy is a minimally invasive procedure for pheochromocytoma with mild symptoms. We believe that this procedure has considerable potential for treating bilateral pheochromocytoma, which is frequently observed in patients with MEN 2a.

  2. Up-regulation of E2F-1 in Down's syndrome brain exhibiting neuropathological features of Alzheimer-type dementia.

    PubMed

    Motonaga, K; Itoh, M; Hirayama, A; Hirano, S; Becker, L E; Goto, Y; Takashima, S

    2001-06-29

    We studied the expression of the apoptosis-related protein, E2F-1, in Down's syndrome (DS) brains. The immunoreactivity for E2F-1 was detected in the pyramidal neurons of the cerebral cortex from DS brains exhibiting the neuropathological features of dementia of Alzheimer type (DAT), in accordance with the amyloid beta protein (A beta) deposition in the neuron. Therefore, the implication is that A beta deposition may trigger E2F-1-mediated neuronal apoptosis in DS brains with DAT.

  3. Photoacoustic microscopy of complex regional pain syndrome type I (CRPS-1) after stellate ganglion blocks in vivo

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

    2015-03-01

    We used photoacoustic microscopy (PAM) to assist diagnoses and monitor the progress and treatment outcome of complex regional pain syndrome type 1 (CRPS-1). Blood vasculature and oxygen saturation (sO2) were imaged by PAM in eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both the vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB.

  4. Recurrent arterial aneurysm rupture of the upper extremity in a patient with vascular-type Ehlers-Danlos syndrome.

    PubMed

    Nakanishi, Koji; Tajiri, Nobuhisa; Nakai, Mikizo; Shimizu, Shuji

    2014-10-01

    Arterial aneurysm rupture is one of the most critical complications in patients with vascular-type Ehlers-Danlos syndrome (vEDS). Here, we report a case of recurrent aneurysm rupture successfully treated by endovascular embolization. A 38-year old woman who underwent brachial artery ligation for a ruptured aneurysm was diagnosed postoperatively with vEDS. Impending rupture of a collateral artery aneurysm was encountered 5 months after the initial open surgery. Endovascular embolization with a liquid embolic agent was successfully performed. Given that arterial rupture can occur repeatedly in patients with vEDS, careful life-long follow-up is necessary.

  5. Endovascular Treatment of a Carotid Dissecting Pseudoaneurysm in a Patient with Ehlers-Danlos Syndrome Type IV with Fatal Outcome

    SciTech Connect

    Lim, Siok Ping Duddy, Martin J.

    2008-01-15

    We present a patient with Ehlers-Danlos syndrome type IV (EDS IV) with a carotid dissecting pseudoaneurysm causing severe carotid stenosis. This lesion was treated endovascularly. Unfortunately, the patient died of remote vascular catastrophes (intracranial hemorrhage and abdominal aortic rupture). This unique case illustrates the perils of endovascular treatment of EDS IV patients and the need for preoperative screening for concomitant lesions. It also shows that a dissecting pseudoaneurysm can feasibly be treated with a covered stent and that closure is effective using Angioseal in patients with EDS IV.

  6. Molecular typing of avian pathogenic Escherichia coli colonies originating from outbreaks of E. coli peritonitis syndrome in chicken flocks.

    PubMed

    Landman, W J M; Buter, G J; Dijkman, R; van Eck, J H H

    2014-01-01

    Escherichia coli colonies isolated from the bone marrow of fresh dead hens of laying flocks with the E. coli peritonitis syndrome (EPS) were genotyped using pulsed-field gel electrophoresis (PFGE). Typing is important from an epidemiological point of view and also if the use of autogenous (auto)vaccines is considered. Birds with EPS originated from one house of each of three layer farms and one broiler breeder farm. Farms were considered as separate epidemiological units. In total, six flocks were examined including two successive flocks of one layer farm and the broiler breeder farm. E. coli colonies (one per bird) from nine to 16 hens of each flock were genotyped. The clonality of E. coli within birds was studied using five colonies of each of nine to 14 birds per flock. E. coli genotypes, which totalled 15, differed between farms and flocks except for two successive layer flocks that shared three genotypes. One to five genotypes were found per flock with one or two genotypes dominating each outbreak. Within hens, E. coli bacteria were always clonal. Colonies of the same PFGE type always had the same multilocus sequence type. However, four PFGE types shared sequence type 95. Neither PFGE types nor multilocus sequence types were unambiguously related to avian pathogenic E. coli from EPS. In cases where persistence of E. coli strains associated with EPS is found to occur frequently, routine genotyping to select strains for autovaccines should be considered.

  7. The Prevalence of Metabolic Syndrome and Its Components among People with Type 2 Diabetes in the Ho Municipality, Ghana: A Cross-Sectional Study

    PubMed Central

    2017-01-01

    The cooccurrence of diabetes mellitus and metabolic syndrome potentiates the cardiovascular risk associated with each of the conditions; therefore characterizing metabolic syndrome among people with type 2 diabetes is beneficial for the purpose of cardiovascular disease prevention. This study aims at evaluating the prevalence of metabolic syndrome and its components among 162 patients with type 2 diabetes attending the diabetic clinic of the Ho Municipal Hospital, Ghana. Data obtained included anthropometric indices, blood pressure, serum lipids, glucose, and sociodemographics and clinical information. The overall prevalence of metabolic syndrome among the study population was 43.83%, 63.58%, and 69.14% using the NCEP-ATP III, the WHO, and the IDF criteria, respectively. The most predominant component among the study population was high blood pressure using the NCEP-ATP III (108 (66.67%)) and WHO (102 (62.96)) criteria and abdominal obesity (112 (69.14%)) for IDF criteria. High blood pressure was the most prevalent component among the males while abdominal obesity was the principal component among the females. In this population with type 2 diabetes, high prevalence of metabolic syndrome exists. Gender vulnerability to metabolic syndrome and multiple cluster components were skewed towards the female subpopulation with type 2 diabetes. PMID:28293668

  8. Rheumatologic and neurological events in an elderly patient with tricho-rhino-phalangeal syndrome type I.

    PubMed

    Rué, Marjory; Lüdecke, Hermann-Josef; Sibon, Igor; Richez, Christophe; Taine, Laurence; Foubert-Samier, Alexandra; Arveiler, Benoit; Schaeverbeke, Thierry; Lacombe, Didier; Tison, François; Goizet, Cyril

    2011-01-01

    Sparse scalp hair, a peculiar shape of the nose, and cone-shaped epiphyses of the phalanges are the hallmarks of the tricho-rhino-phalangeal syndromes (TRPS). Short stature, hip dysplasia, and malformations of inner organs including mitral valve prolpase have also often been described for these conditions. Here, we described a 64-year-old woman with molecularly proved TRPS I and several atypical late-onset rheumatologic and neurological symptoms.

  9. [Latin American consensus on hypertension in patients with diabetes type 2 and metabolic syndrome].

    PubMed

    López-Jaramillo, Patricio; Sánchez, Ramiro A; Díaz, Margarita; Cobos, Leonardo; Bryce, Alfonso; Parra-Carrillo, José Z; Lizcano, Fernando; Lanas, Fernando; Sinay, Isaac; Sierra, Iván D; Peñaherrera, Ernesto; Benderky, Mario; Schmid, Helena; Botero, Rodrigo; Urina, Manuel; Lara, Joffre; Foos, Milton C; Márquez, Gustavo; Harrap, Stephen; Ramírez, Agustín J; Zanchetti, Alberto

    2014-01-01

    The present document has been prepared by a group of experts, members of Cardiology, Endocrinology, Internal Medicine, Nephrology and Diabetes societies of Latin American countries, to serve as a guide to physicians taking care of patients with diabetes, hypertension and comorbidities or complications of both conditions. Although the concept of metabolic syndrome is currently disputed, the higher prevalence in Latin America of that cluster of metabolic alterations has suggested that metabolic syndrome is useful nosography entity in the context of Latin American medicine. Therefore, in the present document, particular attention is paid to this syndrome in order to alert physicians on a particular high- risk population, usually underestimated and undertreated. These recommendations results from presentation and debates by discussion panels during a 2-day conference held in Bucaramanga, in October 2012, and all the participants have approved the final conclusions. The authors acknowledge that the publication and diffusion of guidelines do not suffice to achieve the recommended changes in diagnostic or therapeutic strategies, and plan suitable interventions overcoming both physicians and patients from effectively adhering to guideline recommendations.

  10. Latin American consensus on hypertension in patients with diabetes type 2 and metabolic syndrome.

    PubMed

    López-Jaramillo, Patricio; Sánchez, Ramiro A; Diaz, Margarita; Cobos, Leonardo; Bryce, Alfonso; Parra Carrillo, Jose Z; Lizcano, Fernando; Lanas, Fernando; Sinay, Isaac; Sierra, Iván D; Peñaherrera, Ernesto; Bendersky, Mario; Schmid, Helena; Botero, Rodrigo; Urina, Manuel; Lara, Joffre; Foss, Milton C; Márquez, Gustavo; Harrap, Stephen; Ramírez, Agustín J; Zanchetti, Alberto

    2013-02-01

    The present document has been prepared by a group of experts, members of cardiology, endocrinology and diabetes societies of Latin American countries, to serve as a guide to physicians taking care of patients with diabetes, hypertension and comorbidities or complications of both conditions. Although the concept of 'metabolic syndrome' is currently disputed, the higher prevalence in Latin America of that cluster of metabolic alterations has suggested that 'metabolic syndrome' is a useful nosographic entity in the context of Latin American medicine. Therefore, in the present document, particular attention is paid to this syndrome in order to alert physicians on a particularly high-risk population, usually underestimated and undertreated. These recommendations result from presentations and debates by discussion panels during a 2-day conference held in Bucaramanga, in October 2012, and all the participants have approved the final conclusions. The authors acknowledge that the publication and diffusion of guidelines do not suffice to achieve the recommended changes in diagnostic or therapeutic strategies, and plan suitable interventions overcoming knowledge, attitude and behavioural barriers, preventing both physicians and patients from effectively adhering to guideline recommendations.

  11. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS).

    PubMed

    Pearson, Toni S; Akman, Cigdem; Hinton, Veronica J; Engelstad, Kristin; De Vivo, Darryl C

    2013-04-01

    Glut1 deficiency syndrome (Glut1 DS) was originally described in 1991 as a developmental encephalopathy characterized by infantile onset refractory epilepsy, cognitive impairment, and mixed motor abnormalities including spasticity, ataxia, and dystonia. The clinical condition is caused by impaired glucose transport across the blood brain barrier. The past 5 years have seen a dramatic expansion in the range of clinical syndromes that are recognized to occur with Glut1 DS. In particular, there has been greater recognition of milder phenotypes. Absence epilepsy and other idiopathic generalized epilepsy syndromes may occur with seizure onset in childhood or adulthood. A number of patients present predominantly with movement disorders, sometimes without any accompanying seizures. In particular, paroxysmal exertional dyskinesia is now a well-documented clinical feature that occurs in individuals with Glut1 DS. A clue to the diagnosis in patients with paroxysmal symptoms may be the triggering of episodes during fasting or exercise. Intellectual impairment may range from severe to very mild. Awareness of the broad range of potential clinical phenotypes associated with Glut1 DS will facilitate earlier diagnosis of this treatable neurologic condition. The ketogenic diet is the mainstay of treatment and nourishes the starving symptomatic brain during development.

  12. [Latin American consensus on hypertension in patients with diabetes type 2 and metabolic syndrome].

    PubMed

    López-Jaramillo, Patricio; Sánchez, Ramiro A; Diaz, Margarita; Cobos, Leonardo; Bryce, Alfonso; Parra-Carrillo, Jose Z; Lizcano, Fernando; Lanas, Fernando; Sinay, Isaac; Sierra, Iván D; Peñaherrera, Ernesto; Bendersky, Mario; Schmid, Helena; Botero, Rodrigo; Urina, Manuel; Lara, Joffre; Foss, Milton C; Márquez, Gustavo; Harrap, Stephen; Ramírez, Agustín J; Zanchetti, Alberto

    2014-04-01

    The present document has been prepared by a group of experts, members of cardiology, endocrinology, internal medicine, nephrology and diabetes societies of Latin American countries, to serve as a guide to physicians taking care of patients with diabetes, hypertension and comorbidities or complications of both conditions. Although the concept of metabolic syndrome is currently disputed, the higher prevalence in Latin America of that cluster of metabolic alterations has suggested that metabolic syndrome is a useful nosography entity in the context of Latin American medicine. Therefore, in the present document, particular attention is paid to this syndrome in order to alert physicians on a particular high-risk population, usually underestimated and undertreated. These recommendations result from presentations and debates by discussion panels during a 2-day conference held in Bucaramanga, in October 2012, and all the participants have approved the final conclusions. The authors acknowledge that the publication and diffusion of guidelines do not suffice to achieve the recommended changes in diagnostic or therapeutic strategies, and plan suitable interventions overcoming knowledge, attitude and behavioural barriers, preventing both physicians and patients from effectively adhering to guideline recommendations.

  13. Mutations in PAX3 that cause Waardenburg syndrome type I: Ten new mutations and review of the literature

    SciTech Connect

    Baldwin, C.T.; Hoth, C.F.; Milunsky, A.

    1995-08-28

    Waardenburg syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary disturbances, and it represents the most common form of inherited deafness in infants. WS type I is characterized by the presence of dystopia canthorum, while individuals with WS type II have normally-located canthi. WS type III is similar to WS type I but is also characterized by musculoskeletal abnormalities. Defects in the PAX3 gene, a transcription factor expressed during embryonic development, have been shown to cause WS types I and III in several families. In contrast, mutations in PAX3 do not cause WS type II, and linkage of the disease to other chromosomal regions has been demonstrated. We describe 10 additional mutations in the PAX3 gene in families with WS type I. Eight of these mutations are in the region of PAX3, where only one mutation has been previously described. These mutations, together with those previously reported, cover essentially the entire PAX3 gene and represent a wide spectrum of mutations that can cause WS type I. Thus far, all but one of the mutations are private; only one mutation has been reported in two apparently unrelated families. Our analysis thus far demonstrates little correlation between genotype and phenotype; deletions of the entire PAX3 gene result in phenotypes indistinguishable from those associated with single-base substitutions in the paired domain or homeodomain of PAX3. Moreover, two similar mutations in close proximity can result in significantly different phenotypes, WS type I in one family and WS type III in another. 47 refs., 3 figs., 5 tabs.

  14. A possible difference in the mechanism for postprandial hypoglycemia associated with dumping syndrome between patients with and without type 2 diabetes.

    PubMed

    Hamasaki, Hidetaka; Moriyama, Sumie; Yanai, Hidekatsu

    2015-01-01

    Dumping syndrome is a complication of gastric surgery including bariatric surgery, and which is induced by rapid gastric emptying and increased intestinal motility. We should note that hypoglycaemia due to dumping syndrome can occur in patients with type 2 diabetes. However, the pathogenesis of dumping syndrome in patients with type 2 diabetes is not fully investigated. We investigated the changes in plasma glucose, serum insulin, plasma glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the 75 g oral glucose tolerance test (OGTT) in 3 patients with and without type 2 diabetes who had gastric surgery. Significant hyperinsulinemia was observed in non-diabetic patients, but not in a diabetic patient. On the other hand, plasma GLP-1 levels significantly increased after glucose intake in a diabetic patient. Increased secretion of GLP-1 may have caused reactive hypoglycaemia in patients with type 2 diabetes undergoing gastric surgery.

  15. Gait Strategy in Patients with Ehlers-Danlos Syndrome Hypermobility Type: A Kinematic and Kinetic Evaluation Using 3D Gait Analysis

    ERIC Educational Resources Information Center

    Galli, Manuela; Cimolin, Veronica; Rigoldi, Chiara; Castori, Marco; Celletti, Claudia; Albertini, Giorgio; Camerota, Filippo

    2011-01-01

    The aim of this study was to quantify the gait patterns of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome (JHS/EDS-HT) hypermobility type, using Gait Analysis. We quantified the gait strategy in 12 JHS/EDS-HT adults individuals (age: 43.08 + 6.78 years) compared to 20 healthy controls (age: 37.23 plus or minus 8.91 years), in…

  16. Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type: a study of intrafamilial and interfamilial variability in 23 Italian pedigrees.

    PubMed

    Castori, Marco; Dordoni, Chiara; Valiante, Michele; Sperduti, Isabella; Ritelli, Marco; Morlino, Silvia; Chiarelli, Nicola; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina

    2014-12-01

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two markedly overlapping heritable connective tissue disorders. The cumulative frequency of JHS and EDS-HT seems high, but their recognition remains an exclusion diagnosis based on different sets of diagnostic criteria. Although proposed by a panel of experts, clinical identity between JHS and EDS-HT is still a matter of debate due to unknown molecular basis. We present 23 families with three or more individuals with a diagnosis of JHS and/or EDS-HT. Rough data from the 82 individuals were used to assess the frequency of major and minor criteria, as well as selected additional features. A series of statistical tools were applied to assess intrafamilial and interfamilial variability, emphasizing intergenerational, and intersex differences. This study demonstrates marked heterogeneity within and between families in terms of agreement of available diagnostic criteria. In 21 pedigrees affected individuals belong to two or three phenotypic sub-categories among JHS, EDS-HT, and JHS + EDS-HT overlap. Intergenerational analysis depicts a progressive shifting, also within the same pedigree, from EDS-HT in childhood, to JHS + EDS-HT in early adulthood and JHS later in life. Female-male ratio is 2.1:1, which results lower than previously observed in unselected patients' cohorts. In these pedigrees, JHS, EDS-HT, and JHS + EDS-HT segregate as a single dominant trait with complete penetrance, variable expressivity, and a markedly evolving phenotype. This study represents a formal demonstration that EDS-HT and JHS contitute the same clinical entity, and likely share the same genetic background, at least, in familial cases.

  17. Lack of consensus on tests and criteria for generalized joint hypermobility, Ehlers-Danlos syndrome: hypermobile type and joint hypermobility syndrome.

    PubMed

    Remvig, Lars; Flycht, Lise; Christensen, Karl B; Juul-Kristensen, Birgit

    2014-03-01

    The objectives of this study were to register clinicians performance and opinion of importance of clinical tests for generalized joint hypermobility (GJH), Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS), and to reach a consensus among clinicians on criteria for diagnosing GJH, EDS-HT and JHS. A panel of clinicians answered questions about how to perform and interpret clinical tests and rated test importance on an 11-box scale. The questionnaire was developed on the basis of information from focus groups and the literature. Cronbach's α was used as a measure of internal consistency/consensus among the panelists. The results showed Cronbach's α on importance score of items for diagnosing GJH, EDS-HT and JHS was 0.61, 0.79, and 0.44, respectively. Panelist-group correlation for the three conditions varied substantially (-0.46 to 0.89, 0.03 to 0.68, and -0.07 to 0.68) indicating heterogeneity among the panelists. There was agreement on which tests to use, but performance of the tests (i.e., the specific maneuvers) varied considerably inclusive use of tests with unknown reliability. Furthermore, agreement on the diagnostic criteria varied. We conclude that the level of consensus for the importance of various items for diagnosing GJH, EDS-HT and JHS, was below the required limit (Cronbach's α >0.90) for clinical decision-making and diagnosing. Consensus on tests and criteria through a Delphi process could not be reached. Better descriptions of, and reliability studies on, test maneuvers and criteria sets for these conditions are needed. Subsequent intensive training and implementation of these tests and criteria, nationally as well as internationally should be established.

  18. Cardiac tamponade due to low-volume effusive constrictive pericarditis in a patient with uncontrolled type II autoimmune polyglandular syndrome.

    PubMed

    Palmer, William C; Kurklinsky, Andrew; Lane, Gary; Ussavarungsi, Kamonpun; Blackshear, Joseph L

    2014-03-01

    Type II autoimmune polyglandular syndrome (APS), a relatively common endocrine disorder, includes primary adrenal insufficiency coupled with type 1 diabetes mellitus and/or autoimmune primary hypothyroidism. Autoimmune serositis, an associated disease, may present as symptomatic pericardial effusion. We present a case of a 54-year old male with APS who developed pericarditis leading to cardiac tamponade with a subacute loculated effusion. After urgent pericardiocentesis intrapericardial pressure dropped to 0, while central venous pressures remain elevated, consistent with acute effusive constrictive pericarditis. Contrast computerized tomography confirmed increased pericardial contrast enhancement. The patient recovered after prolonged inotropic support and glucocorticoid administration. He re-accumulated the effusion 16 days later, requiring repeat pericardiocentesis. Effusive-constrictive pericarditis, an uncommon pericardial syndrome, is characterized by simultaneous pericardial inflammation and tamponade. Prior cases of APS associated with cardiac tamponade despite low volumes of effusion have been reported, albeit without good demonstration of hemodynamic findings. We report a case of APS with recurrent pericardial effusion due to pericarditis and marked hypotension with comprehensive clinical and hemodynamic assessment. These patients may require aggressive support with pericardiocentesis, inotropes, and hormone replacement therapy. They should be followed closely for recurrent tamponade.

  19. Tarsal Tunnel Syndrome Due To Three Different Types of Ganglion During a 12-Year Period: A Case Report.

    PubMed

    Kawakatsu, Motohisa; Ishiko, Toshihiro; Sumiya, Masafumi

    A 52-year-old male complained of numbness and radiating pain affecting the plantar region of his left foot. He was found to have recurrent tarsal tunnel syndrome due to posterior tibial nerve compression by 3 different types of ganglion during a 12-year period. To the best of our knowledge, a similar case has not been documented. At the first operation, flexor retinaculum release and simple excision of an epineural ganglion were performed without injuring the nerve fascicles; however, an intrafascicular ganglion developed approximately 2 years later. At the second operation, the ganglion cyst was resected completely to prevent recurrence, despite the risk of nerve fiber injury. The cyst originated from the subtalar joint; thus, the joint was closed, and a free fat graft was placed to prevent adhesion formation. However, an extraneural ganglion occurred about 3 years later. At the third operation, the cyst was resected completely, and a free periosteal graft was used to close the joint more effectively. No recurrence had developed at 6 years after the third operation. The findings of the present case show the need for long-term monitoring of patients with tarsal tunnel syndrome caused by a ganglion owing to the possibility of recurrence related to different ganglion types.

  20. CASE-REPORT Case study of a patient presenting both type II bipolar affective disorder and Klinefelter syndrome.

    PubMed

    Delavenne, H; Khoury, J M; Thibaut, F; Garcia, F D

    2016-10-17

    Klinefelter syndrome (KS) is the most common sex chromosomal disorder with an estimated prevalence of 1 in 500-1000. Increased incidences of anxiety, depression, substance abuse, psychotic and behavioral disorders, and sexual disorders have been reported in patients with KS. The aim of this case study was to report a case of a man with untreated KS who was also diagnosed with type II bipolar disorder. This case report raises awareness regarding psychiatric diagnoses that may be associated with such a highly prevalent condition. A 46-year-old man who had previously been diagnosed with an untreated KS was examined in our Psychiatric Department with an acute hypomanic episode. Clinical improvement was observed within 4 days and psychiatric symptoms were resolved in 7 days without use of medication. A psychiatric history of a depressive episode and at least two hypomanic episodes, as well as a family history of two relatives diagnosed with bipolar disorder, strongly suggest that our patient has type II bipolar disorder. Bipolar disorder may be a comorbid disorder in patients with KS. Routine screening for mood disorders and appropriate referral and evaluation should be performed. Future genetic research is warranted to explore why some chromosomal abnormalities (e.g., duplications), especially those located on the X chromosome, such as Klinefelter syndrome, may be associated with a bipolar or psychotic disorder in some individuals but not in others.

  1. LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Erdei, Katalin; Kaszás, Nóra; Folyovich, András; Szücs, Anna; Barcs, Gábor; Arányi, Zsuzsanna; Skaliczkis, József; Vadasdi, Károly; Winkler, Gábor

    2014-05-30

    Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.

  2. IgG kappa monoclonal gammopathy of undetermined significance presenting as acquired type III Von Willebrand syndrome.

    PubMed

    Howard, Christin R; Lin, Tara L; Cunningham, Mark T; Lipe, Brea C

    2014-09-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated with hematoproliferative disorders, autoimmune conditions, neoplasia and cardiovascular disorders that often present a diagnostic challenge. Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common causes of AVWS that typically presents later in life with mucocutaneous or postsurgical bleeding and multimers consistent with type I or II von Willebrand disease (VWD). Here, we present the case of a patient with a 32-year history of type III VWD that was ultimately found to be AVWS related to an IgG MGUS. In this case report, we highlight the diagnostic challenges of AVWS to ensure proper identification and potentially lifesaving treatment of this rare disorder.

  3. Laparoscopic Resection of Cholecystocolic Fistula and Subtotal Cholecystectomy by Tri-Staple in a Type V Mirizzi Syndrome

    PubMed Central

    Yetişir, Fahri; Şarer, Akgün Ebru; Acar, Hasan Zafer; Parlak, Omer; Basaran, Basar; Yazıcıoğlu, Omer

    2016-01-01

    The Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct (CBD). We would like to report laparoscopic subtotal cholecystectomy (SC) and resection of cholecystocolic fistula by the help of Tri-Staple™ in a case with type V MS and cholecystocolic fistula, for first time in the literature. A 24-year-old man was admitted to emergency department with the complaint of abdominal pain, intermittent fever, jaundice, and diarrhea. Two months ago with the same complaint, ERCP was performed. Laparoscopic resection of cholecystocolic fistula and subtotal cholecystectomy were performed by the help of Tri-Staple. At the eight-month follow-up, he was symptom-free with normal liver function tests. In a patient with type V MS and cholecystocolic fistula, laparoscopic resection of cholecystocolic fistula and SC can be performed by using Tri-Staple safely. PMID:26904324

  4. A-type lamins and cardiovascular disease in premature aging syndromes.

    PubMed

    Dorado, Beatriz; Andrés, Vicente

    2017-01-10

    Lamin A is a nuclear intermediate filament protein with important structural and regulatory roles in most differentiated mammalian cells. Excessive accumulation of its precursor prelamin A or the mutant form called 'progerin' causes premature aging syndromes. Progeroid 'laminopathies' are characterized by severe cardiovascular problems (cardiac electrical defects, vascular calcification and stiffening, atherosclerosis, myocardial infarction, and stroke) and premature death. Here, we review studies in cell and mouse models and patients that are unraveling how abnormal prelamin A and progerin accumulation accelerates cardiovascular disease and aging. This knowledge is essential for developing effective therapies to treat progeria and may help identify new mechanisms underlying normal aging.

  5. Clinical and intraoral findings of a patient with tricho-rhino-phalangeal syndrome type I.

    PubMed

    Karacay, S; Saygun, I; Tunca, Y; Imirzalioglu, N; Guvenc, G

    2007-03-01

    Tricho-rhino-phalangeal syndrome (TRPS) is a rare and an autosomal dominant disorder having the following characteristics: slowly growing sparse hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum and thin upper lip with vermilion border, protruding ears, cone-shaped epiphyses and swelling. Our report intends to introduce TRPS to the dental literature and to present oral, clinical and radiological data of a patient with TRPS. A rare association of supernumerary teeth was also diagnosed and one of them was extracted as it impeded on the eruption path of left premolar tooth.

  6. The first Japanese case of the arthrochalasia type of Ehlers-Danlos syndrome with COL1A2 gene mutation.

    PubMed

    Hatamochi, Atsushi; Hamada, Takahiro; Yoshino, Makoto; Hashimoto, Takashi

    2014-03-15

    This is the first report for a Japanese case of arthrochalasia type of Ehlers-Danlos syndrome (EDS). A 46-year-old woman consulted us for joint hypermobility and skin hyperextensibility that had been present soon after birth. There was no family history of a similar disease. She was diagnosed as having bilateral congenital hip dislocation and bilateral habitual shoulder dislocation at her childhood. Her skin was velvety, doughy and hyperextensible. She showed hypermobility of the joints of the hands and feet and generalized joint laxity, with no evidence of scoliosis. Electrophoretic analysis of collagenous proteins revealed the presence of an additional band in the position of pNα2(I) in the sample from culture medium of the patient fibroblasts. Analysis of the α2 chains of type I collagen gene, COL1A2, showed a heterozygous G to T transition at the +1 position of the exon 6 donor splice site (c.279+1G>T). This mutation resulted in skipping of exon 6, which leads to deficient processing of the amino-terminal end of proα2(I) chains of type I collagen. Based on these findings, we made a diagnosis of the arthrochalasia type of EDS, which corresponds to EDS type VIIB in the former classification.

  7. [Adult type tethered cord syndrome with chronic attackwise pain in the bilateral feet].

    PubMed

    Harashima, Shiho; Taira, Takaomi; Hori, Tomokatsu

    2004-05-01

    The authors report a case of chronic attackwise pain in the bilateral feet for five years due to tethered cord syndrome. Despite extensive examinations, this condition had been overlooked. The patient is a 21-year-old man. He had suffered attackwise pain resembling sticking a thumbtack in the soles of his feet, since he was 16 years old. The pain appeared several times a day and continued for 30 seconds to 30 minutes for 5 years. Physical examination revealed hammer toes and high-arched feet. The fingers and knee joints showed hyperextension. The neurological findings showed weakness of toe extension, hyporeflexia of deep tendon reflexes in the leg. Mild hypesthesia was seen in the bilateral soles. Myelography showed sacral dural ectasia. Magnetic resonance images showed dorsal displacement of the conus medullaris, the filum terminale and the cauda equina. A computed tomographic scan after myelography also showed a dorsally located thick filum terminale (the diameter is 2 mm). Surgery disclosed thick and tight filum terminale directly under the dura mater. Its flexibility was diminished. Abnormal lesions such as lipoma, spinal dysraphysm, diastematomyelia, myelomeningocele were not observed. After the untethering operation, the pain attacks decreased dramatically. The condition of the present case is adult onset tethered cord Group 2 described by Yamada. When unusual pain is manifested, we always have to keep this syndrome in mind.

  8. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems.

    PubMed

    Williams, Stephen R; Aldred, Micheala A; Der Kaloustian, Vazken M; Halal, Fahed; Gowans, Gordon; McLeod, D Ross; Zondag, Sara; Toriello, Helga V; Magenis, R Ellen; Elsea, Sarah H

    2010-08-13

    Brachydactyly mental retardation syndrome (BDMR) is associated with a deletion involving chromosome 2q37. BDMR presents with a range of features, including intellectual disabilities, developmental delays, behavioral abnormalities, sleep disturbance, craniofacial and skeletal abnormalities (including brachydactyly type E), and autism spectrum disorder. To date, only large deletions of 2q37 have been reported, making delineation of a critical region and subsequent identification of candidate genes difficult. We present clinical and molecular analysis of six individuals with overlapping deletions involving 2q37.3 that refine the critical region, reducing the candidate genes from >20 to a single gene, histone deacetylase 4 (HDAC4). Driven by the distinct hand and foot anomalies and similar cognitive features, we identified other cases with clinical findings consistent with BDMR but without a 2q37 deletion, and sequencing of HDAC4 identified de novo mutations, including one intragenic deletion probably disrupting normal splicing and one intragenic insertion that results in a frameshift and premature stop codon. HDAC4 is a histone deacetylase that regulates genes important in bone, muscle, neurological, and cardiac development. Reportedly, Hdac4(-/-) mice have severe bone malformations resulting from premature ossification of developing bones. Data presented here show that deletion or mutation of HDAC4 results in reduced expression of RAI1, which causes Smith-Magenis syndrome when haploinsufficient, providing a link to the overlapping findings in these disorders. Considering the known molecular function of HDAC4 and the mouse knockout phenotype, taken together with deletion or mutation of HDAC4 in multiple subjects with BDMR, we conclude that haploinsufficiency of HDAC4 results in brachydactyly mental retardation syndrome.

  9. Novel compound heterozygous mutations in DYNC2H1 in a patient with severe short-rib polydactyly syndrome type III phenotype.

    PubMed

    Okamoto, Toshio; Nagaya, Ken; Kawata, Yumi; Asai, Hiroko; Tsuchida, Etsushi; Nohara, Fumikatsu; Okajima, Kazuki; Azuma, Hiroshi

    2015-08-01

    Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.

  10. Breakfast skipping and breakfast type are associated with daily nutrient intakes and metabolic syndrome in Korean adults

    PubMed Central

    Chung, Sang-Jin; Lee, Yoonna; Lee, Seokhwa

    2015-01-01

    BACKGROUND/OBJECTIVES Emerging evidence shows that eating breakfast and breakfast types may be associated with health outcomes and dietary intakes in various populations. The aim of this study was to investigate the association between breakfast types in Korean adults with their daily nutrient intakes and health outcomes. SUBJECTS/METHODS A total of 11,801 20- to 64-year-old adults (age 42.9 ± 11.8 yrs [mean ± standard error of the mean]; male 41.1%, female 58.9%) in 2007-2009 Korean National Health and Nutrition Survey data were divided into 5 groups based on breakfast types in a 24-hr dietary recall: rice with 3 or more side dishes (Rice3+, 35.3%), rice with 0-2 side dishes (Rice0-2, 34.73%), noodles (1.56%), bread and cereal (6.56%), and breakfast skipping (21.63%). Daily nutrient intakes and the risk of metabolic syndrome were compared among five groups. RESULTS Compared with Korean Recommended Nutrient Intake levels, the breakfast-skipping group showed the lowest intake level in most nutrients, whereas the Rice3+ group showed the highest. Fat intake was higher in the bread and noodle groups than in the other groups. When compared with the Rice3+ group, the odds ratios for the risk of obesity and metabolic syndrome were increased in the breakfast skipping, Rice0-2, and noodle groups after controlling for confounding variables. CONCLUSIONS The rice-based breakfast group showed better nutritional status and health outcomes when eating with 3 or more side dishes. Nutrition education is needed to emphasize both the potential advantage of the rice-based, traditional Korean diet in terms of nutritional content and the importance of food diversity. PMID:26060541

  11. Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

    PubMed Central

    García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.

    2015-01-01

    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

  12. Keratitis-ichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43.

    PubMed

    García, Isaac E; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshmi; Olivero, Pablo; Perez-Acle, Tomas; González, Carlos; Sáez, Juan C; Contreras, Jorge E; Martínez, Agustín D

    2015-05-01

    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like the Keratitis-Ichthyosis-Deafness syndrome (KID). Because in the human skin connexin 26 (Cx26) is co-expressed with other connexins, like Cx43 and Cx30, and as the KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild-type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channel (GJC) functions remain unknown. In this study, we demonstrate that syndromic mutations, at the N terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) shows exacerbated hemichannel activity but nonfunctional GJCs; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca(2+) overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin.

  13. High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes

    PubMed Central

    Li, Jer-Chuan; Wu, Du-An; Hou, Jia-Sian; Subeq, Yi-Maun; Chen, Hsin-Dean

    2016-01-01

    Adipocyte fatty acid binding protein (A-FABP) is a key mediator of obesity-related metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM) patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5%) had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P < 0.001) than those without MetS. Female DM persons had higher A-FABP level than man (P < 0.001). No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P < 0.001), logarithmically transformed creatinine (log-creatinine; P < 0.001), female DM patients (P < 0.001), and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P = 0.013) were positively correlated, while albumin (P = 0.004) and glomerular filtration rate (GFR; P = 0.043) were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients. PMID:28042581

  14. Reverse transcription recombinase polymerase amplification assay for the rapid detection of type 2 porcine reproductive and respiratory syndrome virus.

    PubMed

    Wang, Jian-Chang; Yuan, Wan-Zhe; Han, Qing-An; Wang, Jin-Feng; Liu, Li-Bing

    2017-05-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in pigs, and has tremendous negative economic impact on the swine industry worldwide. PRRSV is classified into the two distinct genotypes: type 1 and type 2, and most of the described PRRSV isolates in China are type 2. Rapid and sensitive detection of PRRSV is of great importance for the disease control and regional eradication programs. Recombinase polymerase amplification (RPA) has emerged as a novel isothermal amplification technology for the molecular diagnosis of infectious diseases. In this study, a fluorescence reverse transcription RPA (RT-RPA) assay was developed to detect the type 2 PRRSV using primers and exo probe specific for the viral nucleocapsid gene. The reaction was performed at 40°C within 20min. The RT-RPA assay could detect both the classical (C-PRRSV) and highly pathogenic PRRSV (HP-PRRSV), but there was no cross-reaction to other pathogens. Using the in vitro transcribed PRRSV RNA as template, the analytical sensitivity of RT-RPA was 690 copies. The assay performance was evaluated by testing 60 field samples and compared to real-time RT-PCR. The detection rate of RT-RPA was 86.6% (52/60), while the detection rate of real-time RT-PCR was 83.3% (50/60). This simple, rapid and reliable method could be potentially applied for rapid detection of PRRSV in point-of-care and rural areas.

  15. A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.

    PubMed

    Caratão, Nadine; Cortesão, Catarina S; Reis, Pedro H; Freitas, Raquel F; Jacob, Cristina M A; Pastorino, Antonio C; Carneiro-Sampaio, Magda; Barreto, Vasco M

    2013-08-01

    Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.

  16. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    PubMed

    Matthijs, G; Schollen, E; Van Schaftingen, E; Cassiman, J J; Jaeken, J

    1998-03-01

    Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availability of the genomic sequences of PMM2 allowed us to screen for mutations in 56 CDG1 patients from different geographic origins. By SSCP analysis and by sequencing, we identified 23 different missense mutations and 1 single-base-pair deletion. In total, mutations were found on 99% of the disease chromosomes in CDG1A patients. The R141H substitution is present on 43 of the 112 disease alleles. However, this mutation was never observed in the homozygous state, suggesting that homozygosity for these alterations is incompatible with life. On the other hand, patients were found homozygous for the D65Y and F119L mutations, which must therefore be mild mutations. One particular genotype, R141H/D188G, which is prevalent in Belgium and the Netherlands, is associated with a severe phenotype and a high mortality. Apart from this, there is only a limited relation between the genotype and the clinical phenotype.

  17. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    PubMed Central

    Matthijs, G; Schollen, E; Van Schaftingen, E; Cassiman, J J; Jaeken, J

    1998-01-01

    Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availability of the genomic sequences of PMM2 allowed us to screen for mutations in 56 CDG1 patients from different geographic origins. By SSCP analysis and by sequencing, we identified 23 different missense mutations and 1 single-base-pair deletion. In total, mutations were found on 99% of the disease chromosomes in CDG1A patients. The R141H substitution is present on 43 of the 112 disease alleles. However, this mutation was never observed in the homozygous state, suggesting that homozygosity for these alterations is incompatible with life. On the other hand, patients were found homozygous for the D65Y and F119L mutations, which must therefore be mild mutations. One particular genotype, R141H/D188G, which is prevalent in Belgium and the Netherlands, is associated with a severe phenotype and a high mortality. Apart from this, there is only a limited relation between the genotype and the clinical phenotype. PMID:9497260

  18. Lichen planus and Sjögren-type sicca syndrome in a patient with chronic hepatitis C.

    PubMed

    Tanei, R; Ohta, Y; Katsuoka, K

    1997-01-01

    We report a 54-year-old Japanese male with lichen planus and Sjögren-type sicca syndrome, accompanied by the latent complication of chronic hepatitis C. The patient first showed erythematous and erosive lesions with white irregular striae in the buccal mucous membrane, and blepharitis and hyperemia of conjunctiva in his eyes. He later had two small erosions on the glans penis, and flat-topped violaceous papules on the dorsa manus and nape. A biopsy specimen of the lower lip lesion demonstrated a lichenoid tissue reaction at the basement membrane zone, and lymphocytic focal accumulations in the salivary glands. Immunohistochemical study of this specimen revealed CD45RO- (T) cells associated with the expression of HLA-DR antigens predominantly in both the lichenoid tissue reaction and the lymphocytic sialadenitis. Objective keratoconjunctivitis sicca was confirmed by the Schirmer and Rose-Bengal tests. Anti-DNA antibody was positive; however anti-SS-A, and anti-SS-B antibodies were negative. Increased levels of transaminase enzymes, TTT, ZTT, and IgG were observed in first laboratory examinations; thereafter, antihepatitis C virus (HCV) antibodies and HCV-RNA were detected. The high serum amylase level, in which salivary amylase predominated, was normalized by etretinate therapy in parallel with the clinical improvement of the oral LP lesions. Our case is considered to support the hypothesis that an etiologic association may be present among lichen planus, Sjögren's syndrome, and chronic hepatitis C.

  19. A Neonate with Susceptibility to Long QT Syndrome Type 6 who Presented with Ventricular Fibrillation and Sudden Unexpected Infant Death

    PubMed Central

    Sauer, Charles W.; Marc-Aurele, Krishelle L.

    2016-01-01

    Patient: Female, 19-day Final Diagnosis: 19 day old neonate with susceptibility to Long QT syndrome • ventricular fibrillation Symptoms: Cardiac arrest • cardiac arrhythmia • encephalopathy Medication: — Clinical Procedure: Cardioversion Specialty: Pediatrics and Neonatology Objective: Rare disease Background: This is a case of a neonate with susceptibility to long QT syndrome (LQTS) who presented with a sudden unexpected infant death. Experts continue to debate whether universal electrocardiogram (ECG) screening of all newborns is feasible, practical, and cost-effective. Case Report: A 19-day-old neonate was found unresponsive by her mother. ECG showed ventricular fibrillation and a combination of a lidocaine drip plus multiple defibrillations converted the rhythm to normal sinus. Unfortunately, MRI brain imaging showed multiple infarcts and EEG showed burst suppression pattern with frequent seizures; life supportive treatment was stopped and the infant died. Genetic testing revealed two mutations in the KCNE2 gene consistent with susceptibility to LQTS type 6. Conclusions: We believe this case is the first to demonstrate both a precipitating electrocardiographic and genetic cause of death for an infant with LQTS, showing a cause-and-effect relationship between LQTS mutation, ventricular arrhythmia, and death. We wonder whether universal ECG newborn screening to prevent LQTS death could have saved this baby. PMID:27465075

  20. Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain.

    PubMed Central

    Touraine, R L; Attié-Bitach, T; Manceau, E; Korsch, E; Sarda, P; Pingault, V; Encha-Razavi, F; Pelet, A; Augé, J; Nivelon-Chevallier, A; Holschneider, A M; Munnes, M; Doerfler, W; Goossens, M; Munnich, A; Vekemans, M; Lyonnet, S

    2000-01-01

    Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosomal dominant condition when SOX10 mutations are involved. We report on three unrelated WS4 patients with growth retardation and an as-yet-unreported neurological phenotype with impairment of both the central and autonomous nervous systems and occasionally neonatal hypotonia and arthrogryposis. Each of the three patients was heterozygous for a SOX10 truncating mutation (Y313X in two patients and S251X [corrected] in one patient). The extended spectrum of the WS4 phenotype is relevant to the brain expression of SOX10 during human embryonic and fetal development. Indeed, the expression of SOX10 in human embryo was not restricted to neural-crest-derived cells but also involved fetal brain cells, most likely of glial origin. These data emphasize the important role of SOX10 in early development of both neural-crest-derived tissues, namely melanocytes, autonomic and enteric nervous systems, and glial cells of the central nervous system. PMID:10762540

  1. A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1

    PubMed Central

    Ozturk, A.Taylan; Adibelli, Hamit; Unal, Nurettin; Tukun, Ajlan

    2013-01-01

    Purpose Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). Methods WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. Results A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45th residue of helix 3. Conclusions We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity. PMID:23378733

  2. Dysexecutive behaviour following deep brain lesions--a different type of disconnection syndrome?

    PubMed

    Krause, Martin; Mahant, Neil; Kotschet, Katya; Fung, Victor S; Vagg, Daniel; Wong, Chong H; Morris, John G L

    2012-01-01

    The suppression of automatic prepotent behaviour in favour of more successful, more 'appropriate' behaviour is the primary function of the frontal lobe. Five frontal-subcortical circuits connect the frontal lobe to the basal ganglia and the thalamus. We report 17 patients with small lesions in the downstream structures of the frontal-subcortical circuits displaying severe dysexecutive behaviour. Positron emission tomography (PET) demonstrated hypometabolism of the frontal lobe in some of these patients. The literature on frontal lobe dysfunction after lesions in the basal ganglia and thalamus is discussed and the semiology of frontal lobe dysfunction in relation to the frontal-subcortical circuits is highlighted. Derived from our findings we suggest a disconnection syndrome of the frontal lobe caused by lesions in the downstream structures of the frontal-subcortical circuits.

  3. The Association of Silent Coronary Artery Disease and Metabolic Syndrome in Chinese with Type 2 Diabetes Mellitus

    PubMed Central

    Tsai, Jack C.-R.; Chang, Dao-Ming; Chung, Fu-Mei; Wu, Jung-Chou; Shin, Shyi-Jang; Lee, Yau-Jiunn

    2004-01-01

    OBJECTIVES: Cardiovascular diseases account for approximately 75% of the deaths that occur in patients with diabetes. Because the clinical signs of coronary artery disease (CAD) in diabetic patients are hard to detect and routine screening is costly, it would be of great benefit to try to either prevent CAD from occurring or to detect it early and provide optimal care. Therefore, we analyzed the risk factors that might predict CAD in type 2 diabetes mellitus (T2DM) patients with no classical cardiac ischemic symptoms. METHODS: Using a resting 12-lead ECG, exercise treadmill test, or thallium myocardial scintigraphy with exercise testing and dipyridamole injection, we screened diabetic patients already enrolled in a disease management program for possible CAD. We used diagnostic coronary angiography to confirm its presence. The definition and criteria of metabolic syndrome we used were modified from those outlined by the WHO classification and criteria of NCEP-ATP III. RESULTS: A total of 850 T2DM patients without clinical and electrocardiographic evidence of CAD were studied. Three hundred and sixty-eight asymptomatic patients with normal resting ECG were examined by exercise ECG test or thallium scintigraphy examination. Sixty patients considered to have a strong positive test or significant thallium myocardial ischemia received a diagnostic coronary angiography. Fifty-one were found to have significant coronary artery stenosis; 9 showed no significant ischemic lesion. While gender, patients' age, known diabetes duration, serum uric acid level, smoking status, and the presence of WHO-metabolic syndrome defined hypertension and nephropathy were associated with silent CAD, logistic regression analysis found that the only predictor of silent CAD was the presence of nephropathy. The components of NCEP-ATP III-metabolic syndrome were not found to be associated with silent CAD. CONCLUSIONS: A considerable proportion of T2DM patients have silent CAD. A diabetic patient

  4. Evidence suggesting digenic inheritance of Waardenburg syndrome type II with ocular albinism.

    PubMed

    Chiang, Pei-Wen; Spector, Elaine; McGregor, Tracy L

    2009-12-01

    Waardenburg syndrome (WS) is a series of auditory-pigmentary disorders inherited in an autosomal dominant manner. In most patients, WS2 results from mutations in the MITF gene. MITF encodes a basic helix-loop-helix transcription factor that activates transcription of tyrosinase and other melanocyte proteins. The clinical presentation of WS is highly variable, and we believe that Tietz syndrome and WS2 with ocular albinism (OA) are likely two variations of WS2 due to the presence of modifiers. One family with a molecular diagnosis of WS2 co-segregating with OA has previously been reported. A digenic mutation mechanism including both a MITF mutation and the TYR(R402Q) hypomorphic allele was proposed to be the cause of OA in this family. Here, we present a second WS2 family with OA and provide evidence suggesting the TYR(R402Q) allele does not cause OA in this family. We hypothesize the presence of a novel OCA3 mutation together with the MITF del p.R217 mutation account for the OA phenotype in this family. Since MITF is a transcription factor for pigmentation genes, a mutation in MITF plus a heterozygous mutation in OCA3 together provide an adverse effect crossing a quantitative threshold; therefore, WS2 with OA occurs. We have hypothesized previously that the clinical spectrum and mutation mechanism of OCA depend on the pigmentation threshold of an affected individual. This unique family has provided further evidence supporting this hypothesis. We suggest that by studying OCA patients alongside WS patients with various pigmentation profiles we can facilitate further understanding of the pigmentation pathway.

  5. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    PubMed Central

    Hogan, P; Oliver, T

    2016-01-01

    Summary A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases. Learning points A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome. Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease. Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism. PMID:27482386

  6. Shoulder function, pain and health related quality of life in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome-hypermobility type.

    PubMed

    Johannessen, Elise Christine; Reiten, Helle Sundnes; Løvaas, Helene; Maeland, Silje; Juul-Kristensen, Birgit

    2016-07-01

    Purpose To investigate shoulder function, pain and Health-Related Quality of life (HRQoL) among adults with joint hypermobility syndrome/Ehlers-Danlos syndrome-hypermobility type (JHS/EDS-HT), compared with the general population (controls). Method In a cross-sectional study using postal survey, 110 patients diagnosed with JHS/EDS-HT and 140 gender- and age-matched healthy controls from Statistics Norway participated. Shoulder function, pain and HRQol were registered by Western Ontario Shoulder Instability Index (WOSI), Numerical Rating Scale (NRS), pain drawings, 36-item Short Form (SF-36). Results Eighty-one individuals responded, with response rate 34% (JHS/EDS-HT: 53%, controls: 21%). JHS/EDS-HT had lower shoulder function (WOSI total: 49.9 versus 83.3; p < 0.001), lower HRQol on SF-36 Physical Component Scale (PCS: 28.1 versus 49.9; p < 0.001), and higher pain intensity (NRS: 6.4 versus 2.7; p < 0.001) than controls. Neck and shoulder joints were rated as primary painful areas in both groups, with significantly higher frequency in JHS/EDS-HT (neck: 90% versus 27%; shoulder: 80% versus 37%). Further, JHS/EDS-HT most often reported generalized pain (96%). Conclusions Adults with JHS/EDS-HT have impaired shoulder function, increased pain intensity, as well as reduced physical HRQoL compared with controls. Although neck and shoulder were most frequently rated as painful, significantly more JHS/EDS-HT also reported generalized pain compared to controls. Implications for Rehabilitation Adults with JHS/EDS-HT have impaired shoulder function, and most often painful areas in the neck and shoulder joints, which need to be targeted in the treatment strategy. Compared with the general population adults with JHS/EDS-HT have reduced physical HRQoL, supporting a physical approach for this group. Adults with JHS/EDS-HT may present with both specific painful joints and generalized pain.

  7. Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome.

    PubMed

    Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2015-01-01

    Fragile X syndrome (FXS) is caused by transcriptional silencing of the fmr1 gene resulting in the loss of fragile X mental retardation protein (FMRP) expression. FXS patients display several behavioral phenotypes associated with prefrontal cortex (PFC) dysfunction. Voltage-gated ion channels, some of which are regulated by FMRP, heavily influence PFC neuron function. Although there is evidence for brain region-specific alterations to the function a single type of ion channel in FXS, it is unclear whether subtypes of principal neurons within a brain region are affected uniformly. We tested for alterations to ion channels critical in regulating neural excitability in two subtypes of prefrontal L5 pyramidal neurons. Using somatic and dendritic patch-clamp recordings, we provide evidence that the functional expression of h-channels (Ih) is down-regulated, whereas A-type K(+) channel function is up-regulated in pyramidal tract-projecting (PT) neurons in the fmr1-/y mouse PFC. This is the opposite pattern of results from published findings from hippocampus where Ih is up-regulated and A-type K(+) channel function is down-regulated. Additionally, we find that somatic Kv1-mediated current is down-regulated, resulting in increased excitability of fmr1-/y PT neurons. Importantly, these h- and K(+) channel differences do not extend to neighboring intratelencephalic-projecting neurons. Thus, the absence of FMRP has divergent effects on the function of individual types of ion channels not only between brain regions, but also variable effects across cell types within the same brain region. Given the importance of ion channels in regulating neural circuits, these results suggest cell-type-specific phenotypes for the disease.

  8. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    SciTech Connect

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. )

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  9. A syndrome of hypotonia, psychomotor retardation, seizures, delayed and dysharmonic skeletal maturation, and congenital fibre type disproportion.

    PubMed Central

    Qazi, Q H; Markouizos, D; Rao, C; Sheikh, T; Beller, E; Kula, R

    1994-01-01

    Three unrelated Puerto Rican boys, ranging in age from 3 to 4 years, had marked, central, non-progressive hypotonia, chronic constipation, severe psychomotor retardation, seizures or abnormal electroencephalograph or both, abnormal dermatoglyphics, delayed bone age, dysharmonic skeletal maturation, and preponderance and larger size of type 2 muscle fibres. Additional findings included narrow, high arched palate, prominent nasal root, long philtrum, distended abdomen, and drooling from open mouth. Two of the three patients also had undescended testes, hypertelorism, and tapered fingers. Birth weight, postnatal physical growth, and head size were average. Family and gestational histories and laboratory evaluations were normal. The combination of features observed in the three boys appears to be distinct and to represent a new syndrome. Images PMID:8064821

  10. Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study

    SciTech Connect

    Rakovec, P.; Kranjec, I.; Fettich, J.J.; Jakopin, J.; Fidler, V.; Turk, J.

    1985-01-01

    Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combined electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates.

  11. Apparent non-penetrance for dystopia in Waardenburg syndrome type I, with some hints on the diagnosis of dystopia canthorum.

    PubMed

    Arias, S; Mota, M

    1978-06-01

    Two large pedigrees with Waardenburg syndrome type I (W--I), i.e. with dystopia canthorum and blepharophimosis, are described to show both the variable expressivity of dystopia canthorum, which may be confused with non-penetrance of this sign, and the possibility to firmly diagnosis it with the new biometric index W, which differentiates a dystopic from a non-dystopic or a non-apparent dystopic subject, the latter within a defined biometric range. A general discussion of the relative value of blepharophimosis and dystopia canthorum as diagnostic features in W--I is presented, to conclude on the greater value of dystopia canthorum, which can be identified with confidence in more than 96% of carriers. Empirical probabilities are given for dystopia canthorum and blepharophimosis in the general populations, based on data from the world literature, useful for all ethnic groups.

  12. Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases

    PubMed Central

    Shpakov, Alexander O; Derkach, Kira V; Berstein, Lev M

    2015-01-01

    The changes in the brain signaling systems play an important role in etiology and pathogenesis of Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), being a possible cause of these diseases. Therefore, their restoration at the early stages of T2DM and MS can be regarded as a promising way to treat and prevent these diseases and their complications. The data on the functional state of the brain signaling systems regulated by insulin, IGF-1, leptin, dopamine, serotonin, melanocortins and glucagon-like peptide-1, in T2DM and MS, are analyzed. The pharmacological approaches to restoration of these systems and improvement of insulin sensitivity, energy expenditure, lipid metabolism, and to prevent diabetic complications are discussed. PMID:28031898

  13. Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

    SciTech Connect

    Peppa, Melpomeni; Brountzos, Elias; Economopoulos, Nicolaos; Boutati, Eleni; Pikounis, Vasilios; Patapis, Paul; Economopoulos, Theofanis; Raptis, Sotirios A.; Hadjidakis, Dimitrios

    2009-07-15

    Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

  14. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature

    PubMed Central

    Rice, Gillian I; Kasher, Paul R; Forte, Gabriella M A; Mannion, Niamh M; Greenwood, Sam M; Szynkiewicz, Marcin; Dickerson, Jonathan E; Bhaskar, Sanjeev S; Zampini, Massimiliano; Briggs, Tracy A; Jenkinson, Emma M; Bacino, Carlos A; Battini, Roberta; Bertini, Enrico; Brogan, Paul A; Brueton, Louise A; Carpanelli, Marialuisa; Laet, Corinne De; de Lonlay, Pascale; del Toro, Mireia; Desguerre, Isabelle; Fazzi, Elisa; Garcia-Cazorla, Àngels; Heiberg, Arvid; Kawaguchi, Masakazu; Kumar, Ram; Lin, Jean-Pierre S-M; Lourenco, Charles M; Male, Alison M; Marques, Wilson; Mignot, Cyril; Olivieri, Ivana; Orcesi, Simona; Prabhakar, Prab; Rasmussen, Magnhild; Robinson, Robert A; Rozenberg, Flore; Schmidt, Johanna L; Steindl, Katharina; Tan, Tiong Y; van der Merwe, William G; Vanderver, Adeline; Vassallo, Grace; Wakeling, Emma L; Wassmer, Evangeline; Whittaker, Elizabeth; Livingston, John H; Lebon, Pierre; Suzuki, Tamio; McLaughlin, Paul J; Keegan, Liam P; O’Connell, Mary A; Lovell, Simon C; Crow, Yanick J

    2014-01-01

    Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) and thereby potentially alter the information content and structure of cellular RNAs. Notably, although the overwhelming majority of such editing events occur in transcripts derived from Alu repeat elements, the biological function of non-coding RNA editing remains uncertain. Here, we show that mutations in ADAR1 (also known as ADAR) cause the autoimmune disorder Aicardi-Goutières syndrome (AGS). As in Adar1-null mice, the human disease state is associated with upregulation of interferon-stimulated genes, indicating a possible role for ADAR1 as a suppressor of type I interferon signaling. Considering recent insights derived from the study of other AGS-related proteins, we speculate that ADAR1 may limit the cytoplasmic accumulation of the dsRNA generated from genomic repetitive elements. PMID:23001123

  15. Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells

    PubMed Central

    Keppel Hesselink, Jan M; Kopsky, David J

    2013-01-01

    Chronic regional pain syndrome (CRPS) can be intractable to treat and patients sometimes suffer for many years. Therefore, new treatment strategies are needed to alleviate symptoms in CRPS patients. This case report describes a patient suffering from intractable CRPS type 1 for 13 years. Due to her swollen painful feet and left knee she is wheelchair-bound. The combination of palmitoylethanolamide and ketamine 10% cream reduced her pain by more than 50% after 1 month of treatment, and a marked reduction in swelling and skin discoloration was noticed. Furthermore, she could walk independently again and she experienced no side effects. Thus, palmitoylethanolamide and topical ketamine could be a combination therapy option for treating CRPS patients. PMID:23658493

  16. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED): A “Rare” Manifestation in a “Rare” Disease

    PubMed Central

    Fierabracci, Alessandra

    2016-01-01

    Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome. PMID:27420045

  17. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

    PubMed Central

    2011-01-01

    Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

  18. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1).

    PubMed

    Giusti, Francesca; Cianferotti, Luisella; Gronchi, Giorgio; Cioppi, Federica; Masi, Laura; Faggiano, Antongiulio; Colao, Annamaria; Ferolla, Piero; Brandi, Maria Luisa

    2016-06-01

    Primary hyperparathyroidism is the main endocrinopathy associated with Multiple Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease, and for the reduction of marked hypercalcemia in patients with parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for whom parathyroidectomy is contraindicated. It may provide a medical alternative for the management of primary hyperparathyroidism in subjects affected by Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33 MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 ± 11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day, 22 patients starting therapy with calcimimetics as an alternative to surgery, and 11 patients opting for the medication after the onset of persistent post-surgical primary hyperparathyroidism. Duration of follow-up was 12 months. The results of this study show significant reductions in serum calcium. The changes in hormonal secretions of pituitary and gastroenteropancreatic glands were not significant, demonstrating the overall safety of this drug in this disease. Cinacalcet has been well tolerated by 28 patients, whereas five individuals complained of heartburn and grade 1 nausea, which did not prevent the completion of the study. In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients with MEN1 syndrome and the calcium homeostasis was stabilized.

  19. Loss of Type I Collagen Telopeptide Lysyl Hydroxylation Causes Musculoskeletal Abnormalities in a Zebrafish Model of Bruck Syndrome

    PubMed Central

    Gistelinck, Charlotte; Witten, Paul Eckhard; Huysseune, Ann; Symoens, Sofie; Malfait, Fransiska; Larionova, Daria; Simoens, Pascal; Dierick, Manuel; Van Hoorebeke, Luc; De Paepe, Anne; Kwon, Ronald Y; Weis, MaryAnn; Eyre, David R; Willaert, Andy; Coucke, Paul J

    2017-01-01

    Bruck syndrome (BS) is a disorder characterized by joint flexion contractures and skeletal dysplasia that shows strong clinical overlap with the brittle bone disease Osteogenesis Imperfecta (OI). BS is caused by bi-allelic mutations in either the FKBP10 or the PLOD2 gene. PLOD2 encodes the lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of lysine residues in fibrillar collagen telopeptides. This hydroxylation directs cross-linking of collagen fibrils in the extracellular matrix, which is necessary to provide stability and tensile integrity to the collagen fibrils. To further elucidate the function of LH2 in vertebrate skeletal development, we created a zebrafish model harboring a homozygous plod2 nonsense mutation resulting in reduced telopeptide hydroxylation and cross-linking of bone type I collagen. Adult plod2 mutants present with a shortened body axis and severe skeletal abnormalities with evidence of bone fragility and fractures. The vertebral column of plod2 mutants is short and scoliotic with compressed vertebrae that show excessive bone formation at the vertebral end plates, and increased tissue mineral density in the vertebral centra. The muscle fibers of mutant zebrafish have a reduced diameter near the horizontal myoseptum. The endomysium, a layer of connective tissue ensheathing the individual muscle fibers, is enlarged. Transmission electron microscopy of mutant vertebral bone shows type I collagen fibrils that are less organized with loss of the typical plywood-like structure. In conclusion, plod2 mutant zebrafish show molecular and tissue abnormalities in the musculoskeletal system that are concordant with clinical findings in BS patients. Therefore, the plod2 zebrafish mutant is a promising model for the elucidation of the underlying pathogenetic mechanisms leading to BS and the development of novel therapeutic avenues in this syndrome. PMID:27541483

  20. The existence of Usher syndrome type III proven by assignment of its locus to chromosome 3q by linkage

    SciTech Connect

    Sankila, E.M.; Aittomaeki, K.; Kaeaeriaeinen, H.

    1994-09-01

    Usher syndromes (USH) are genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Usher syndrome type III (USH3) is characterized by progressive bilateral sensorineural deafness and progressive pigmentary retinopathy leading to blindness. USH3 has been conservatively estimated to comprise 2% of the three clinical USH types, and its existence has even been questioned. However, based on clinical criteria, in Finland 42% of USH patients have USH3 suggesting gene enrichment by a founder effect. Genes whose defects cause USH have so far been mapped to four different locations in three chromosomes. We have excluded the previously mapped USH regions as the site of USH3 disease locus. Systematic search for USH3 by genetic linkage analyses of 11 multiple affected families using highly polymorphic microsatellite markers revealed significant linkage with five markers mapping to chromosome 3q. Two-point lod scores at zero recombination distance were 5.24 for D3S1308, and 7.71 for D3S1299, respectively. Multipoint linkage analysis gave a maximum lod score of 8.68 at D3S1299 assigning USH3 to the 4 cM interval between markers D3S1555 and D3S1279 in 3q21-25. Of 20 parental disease chromosomes, 15 had identical alleles at three marker loci covering 3 cM genetic distance and the putative USH3 mutation. These findings prove the existence of USH3 as a distinct entity, pinpoint a fifth USH locus, and suggest enrichment of a major mutation in the isolated Finnish population.

  1. Hearing loss in the RBF/DnJ mouse, a proposed animal model of Usher syndrome type IIa.

    PubMed

    Pieke-Dahl, S; Ohlemiller, K K; McGee, J; Walsh, E J; Kimberling, W J

    1997-10-01

    The Usher syndromes (US) are a group of inherited disorders that feature autosomal recessive neurosensory hearing loss or deafness with retinitis pigmentosa (RP). Moderate to severe non-progressive high frequency hearing loss with RP and normal vestibular function describes Usher syndrome type IIa, which has been localized to 1q41. Severe retinal degeneration in the inbred mouse strain RBF/DnJ is caused by rd3, a recessive gene located on mouse chromosome 1 distal to akp1 in a region which is orthologous to human 1q32-q42. We evaluated rd3 as a candidate for orthology with USH2A by first reducing and refining the relatively broad region in which rd3 is thought to reside. DNA of offspring from an RBF/DnJ x MOLF/Ei backcross was genotyped with PCR markers closely flanking the predicted location of rd3. Our haplotype analysis re-positioned rd3 to a 3.6 cM region between markers D1Mit273 (cen) and D1Mit209 (tel), consistent with the expected position of an USH2A murine orthologue. Consequently, rd3 is a positional candidate for Usher type IIa. Next we assessed the rd3/rd3 audiological phenotype to see how closely it paralleled that of Usher IIa. Audiological evaluation of mice at various ages revealed evidence of high frequency progressive hearing loss, previously unreported in the RBF/DnJ strain. However, this newly discovered hearing deficit was observed to be inherited independently of rd3, establishing that a completely different gene is responsible.

  2. Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.

    PubMed

    Canals, I; Elalaoui, S C; Pineda, M; Delgadillo, V; Szlago, M; Jaouad, I C; Sefiani, A; Chabás, A; Coll, M J; Grinberg, D; Vilageliu, L

    2011-10-01

    The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. We report the first molecular study on several Spanish Sanfilippo syndrome type C patients. Seven Spanish patients, one Argentinean and three Moroccan patients were analysed. All mutant alleles were identified and comprised nine distinct mutant alleles, seven of which were novel, including four missense mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due to two point mutations (c.633+1G>A and c.1378-1G>A) and an intronic deletion (c.821-31_821-13del). Furthermore, we found a new single nucleotide polymorphism (SNP) (c.564-98T>C). The two most frequent changes were the previously described c.372-2A>G and c.234+1G>A mutations. All five splicing mutations were experimentally confirmed by studies at the RNA level, and a minigene experiment was carried out in one case for which no fibroblasts were available. Expression assays allowed us to show the pathogenic effect of the four novel missense mutations and to confirm that the already known c.710C>A (p.P237Q) is a non-pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A and c.372-2A>G) that were present in more than one patient have a common origin, including one (c.234+1G>A) that was found in Spanish and Moroccan patients.

  3. Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome

    NASA Astrophysics Data System (ADS)

    Anderson, Corey L.; Kuzmicki, Catherine E.; Childs, Ryan R.; Hintz, Caleb J.; Delisle, Brian P.; January, Craig T.

    2014-11-01

    It has been suggested that deficient protein trafficking to the cell membrane is the dominant mechanism associated with type 2 Long QT syndrome (LQT2) caused by Kv11.1 potassium channel missense mutations, and that for many mutations the trafficking defect can be corrected pharmacologically. However, this inference was based on expression of a small number of Kv11.1 mutations. We performed a comprehensive analysis of 167 LQT2-linked missense mutations in four Kv11.1 structural domains and found that deficient protein trafficking is the dominant mechanism for all domains except for the distal carboxy-terminus. Also, most pore mutations—in contrast to intracellular domain mutations—were found to have severe dominant-negative effects when co-expressed with wild-type subunits. Finally, pharmacological correction of the trafficking defect in homomeric mutant channels was possible for mutations within all structural domains. However, pharmacological correction is dramatically improved for pore mutants when co-expressed with wild-type subunits to form heteromeric channels.

  4. A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report

    PubMed Central

    SHI, YUNFANG; LI, XIAOZHOU; JU, DUAN; LI, YAN; ZHANG, XIULING; ZHANG, YING

    2016-01-01

    Waardenburg syndrome (WS) is an autosomal dominant disorder with varying degrees of sensorineural hearing loss, and accumulation of pigmentation in hair, skin and iris. There are four types of WS (WS1–4) with differing characteristics. Mutations in six genes [paired box gene 3 (PAX3), microphthalmia-associated transcription factor (MITF), endothelin 3 (END3), endothelin receptor type B (EDNRB), SRY (sex determining region Y)-box 10 (SOX10) and snail homolog 2 (SNAI2)] have been identified to be associated with the various types. This case report describes the investigation of genetic mutations in three patients with WS2 from a single family. Genomic DNA was extracted, and the six WS-related genes were sequenced using next-generation sequencing technology. In addition to mutations in PAX3, EDNRB and SOX10, a novel heterozygous MITF mutation, p.Δ315Arg (c.944_946delGAA) on exon 8 was identified. This is predicted to be a candidate disease-causing mutation that may affect the structure and function of the enzyme. PMID:27073475

  5. Defects of B Cell Terminal Differentiation in Patients with Type-1 Kabuki Syndrome

    PubMed Central

    Lindsley, Andrew W.; Saal, Howard M.; Burrow, Thomas A.; Hopkin, Robert J.; Shchelochkov, Oleg; Khandelwal, Pooja; Xie, Changchun; Bleesing, Jack; Filipovich, Lisa; Risma, Kimberly; Assa’ad, Amal H.; Roehrs, Phillip A.; Bernstein, Jonathan A.

    2015-01-01

    Background Kabuki syndrome (KS) is a complex multi-system developmental disorder associated with mutation of genes encoding histone-modifying proteins. In addition to craniofacial, intellectual, and cardiac defects, KS is also characterized by humoral immune deficiency and autoimmune disease, yet no detailed molecular characterization of the KS-associated immune phenotype has previously been reported. Objective To characterize the humoral immune defects found in KS patients with KMT2D mutations. Methods We comprehensively characterize B cell function in a cohort (N = 13) of patients with KS (ages 4 months to 27 years). Results Three-quarters (77%) of the cohort had a detectable heterozygous KMT2D mutations (50% nonsense, 20% splice site, 30% missense), and 70% of the reported mutations are novel. Amongst the patients with KMT2D mutations (KMT2DMut/+), hypogammaglobulinemia was detected in all but one individual, with IgA deficiency affecting 90% of patients and a deficiency in at least one other isoform seen in 40% of patients. Total memory (CD27+) and class-switched memory B cells (IgM−) were significantly reduced in KMT2DMut/+ patients compared to controls (p-values < 0.001). KMT2DMut/+ patients also had significantly reduced rates of somatic hypermutation in IgG (p value = 0.003), but not IgA or IgM heavy chain sequences. Impaired terminal differentiation was noted in KMT2DMut/+ primary B cells. Autoimmune pathology was observed in patients with missense mutations affecting the SET domain and its adjacent domains. Conclusions In patients with KS, autosomal dominant KMT2D mutations are associated with the dysregulation of terminal B cell differentiation leading to humoral immune deficiency and in some cases autoimmunity. All patients with KS should undergo serial clinical immune evaluations. Clinical Implications KMT2DMut/+ Kabuki syndrome causes IgA deficiency in nearly all patients, although additional humoral defects (memory B cell deficiency, Ig

  6. Assessment of Serum VASPIN Levels among Type 2 Diabetes Mellitus Patients with or without Acute Coronary Syndrome

    PubMed Central

    Sathyaseelan, Aswathy Jaya; Wyawahare, Mukta; Saya, Rama Prakasha

    2016-01-01

    Introduction Type 2 Diabetes Mellitus (DM) is on the verge of becoming a pandemic in India. Type 2 DM patient have two to four times increased risk of carotid artery disease. Adipokines have been regarded recently as direct link between diabetes and atherosclerosis. Visceral Adipose Tissue Derived Serine Protease Inhibitor (VASPIN); one of the most recently discovered adipokine, inhibits the proteases responsible for insulin resistance, carotid plaque development and rupture. In literature, few studies have addressed the role of VASPIN in pathogenesis of Acute Coronary Syndrome (ACS) in patients with type 2 DM. Aim To find association between serum VASPIN with lipid profile, creatine kinase-total, creatine kinase-MB, troponin-I, age, height, weight, blood pressure, smoking, family history of ACS and to prove the hypothesis of low serum VASPIN level as predictor of ACS in patients with type 2 DM. Materials and Methods Forty-one type 2 DM patients (controls) and 41 type 2 DM patients with ACS (cases) were enrolled in the study. Anthropometric measurements were performed and fasting serum biochemical parameters and VASPIN were measured. The results of cases and controls were compared by student t-test or Mann–Whitney test. All the parameters were correlated with serum VASPIN by Pearson’s or Spearman’s correlation. Results Fasting serum VASPIN concentration was significantly (p< 0.0001) lower in the cases (0.43±0.22 pg/ml) than in the controls (0.83±0.29 pg/ml). Correlation analysis undertaken on all type 2 DM showed that serum VASPIN concentration was negatively correlated with age, waist circumference, hip circumference, systolic and diastolic blood pressure, duration of diabetes, serum Creative Kinase-Total, CK-MB and urea (p< 0.05). Utilizing Receiver Operating Characteristic (ROC) curve, the serum VASPIN level of less than 0.594pg/ml showed greatest risk of ACS among type 2 DM patients (p< 0.0001). Conclusion Type 2 DM patients with low serum vaspin

  7. Hemizygosity for SMCHD1 in facioscapulohumeral muscular dystrophy type 2: Consequences for 18p deletion syndrome

    PubMed Central

    Lemmers, Richard J.L.F.; van den Boogaard, Marlinde L.; van der Vliet, Patrick J.; Donlin-Smith, Colleen M.; Nations, Sharon P.; Ruivenkamp, Claudia A.L.; Heard, Patricia; Bakker, Bert; Tapscott, Stephen; Cody, Jannine D.; Tawil, Rabi; van der Maarel, Silvère M.

    2015-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is most often associated with variegated expression in somatic cells of the normally repressed DUX4 gene within the D4Z4 repeat array. The most common form, FSHD1, is caused by a D4Z4 repeat array contraction to a size of 1-10 units (normal range 10–100 units). The less common form, FSHD2, is characterized by D4Z4 CpG hypomethylation and is most often caused by loss of function mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene on chromosome 18p. The chromatin modifier SMCHD1 is necessary to maintain a repressed D4Z4 chromatin state. Here we describe two FSHD2 families with a 1.2 Mb deletion encompassing the SMCHD1 gene. Numerical aberrations of chromosome 18 are relatively common and the majority of 18p deletion syndrome (18p-) cases have, like these FSHD2 families, only one copy of SMCHD1. Our finding therefore raises the possibility that 18p- cases are at risk of developing FSHD. To address this possibility, we combined genome wide array analysis data with D4Z4 CpG methylation and repeat array sizes in individuals with 18p- and conclude that approximately 1:8 18p- cases might be at risk of developing FSHD. PMID:25820463

  8. Hepcidin levels and their determinants in different types of myelodysplastic syndromes.

    PubMed

    Santini, Valeria; Girelli, Domenico; Sanna, Alessandro; Martinelli, Nicola; Duca, Lorena; Campostrini, Natascia; Cortelezzi, Agostino; Corbella, Michela; Bosi, Alberto; Reda, Gianluigi; Olivieri, Oliviero; Cappellini, Maria Domenica

    2011-01-01

    Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic non-transferrin-bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiation factor 15 did not appear as a primary hepcidin regulator in this series. If confirmed, these results may help to calibrate future treatments with chelating agents and/or hepcidin modulators in MDS patients.

  9. Multivariate linkage scan for metabolic syndrome traits in families with type 2 diabetes.

    PubMed

    Edwards, Karen L; Wan, Jia Y; Hutter, Carolyn M; Fong, Pui Yee; Santorico, Stephanie A

    2011-06-01

    The purpose of this study was to evaluate evidence for linkage to interrelated quantitative features of the metabolic syndrome (MetS). Data on eight quantitative MetS traits (body weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein (HDL) cholesterol, triglycerides (TGs), and fasting glucose and insulin measurements) and a 10 cM genome scan were available for 78 white families (n = 532 subjects). These data were used to conduct multipoint, multivariate linkage analyses, including tests for coincident linkage and complete pleiotropy. The strongest evidence for linkage from the bivariate analyses was observed on chromosome 1 (1p22.2) (HDL-TG; univariate lod score equivalent (lod(eq) = 3.99)) with stronger results from the trivariate analysis at the same location (HDL-TG-Insulin; lod(eq) = 4.32). Seven additional susceptibility regions (lod(eq) scores >1.9) were observed (1p36, 1q23, 2q21.2, 8q23.3, 14q23.2, 14q32.11, and 20p11.21). The results from this study indicate that several correlated traits of the MetS are influenced by the same gene(s) that account for some of the clustering of the MetS features.

  10. Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5

    PubMed Central

    O’Brien, Kevin J.; Nicoli, Elena-Raluca; Brooks, Brian P.; Huryn, Laryssa; Titus, Steven A.; Adams, David R.; Chen, Dong; Gahl, William A.; Gochuico, Bernadette R.

    2017-01-01

    Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of genetic disorders typically manifesting with tyrosinase-positive oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis, in some subtypes. Most HPS subtypes are associated with defects in Biogenesis of Lysosome-related Organelle Complexes (BLOCs), which are groups of proteins that function together in the formation and/or trafficking of lysosomal-related endosomal compartments. BLOC-2, for example, consists of the proteins HPS3, HPS5, and HPS6. Here we present an HPS patient with defective BLOC-2 due to a novel intronic mutation in HPS5 that activates a cryptic acceptor splice site. This mutation leads to the insertion of nine nucleotides in-frame and results in a reduced amount of HPS5 at the transcript and protein level. In studies using skin fibroblasts derived from the proband and two other individuals with HPS-5, we found a perinuclear distribution of acidified organelles in patient cells compared to controls. Our results suggest the role of HPS5 in the endo-lysosomal dynamics of skin fibroblasts. PMID:28296950

  11. Type B insulin resistance syndrome induced by systemic lupus erythematosus and successfully treated with intravenous immunoglobulin: case report and systematic review.

    PubMed

    Zhang, Sigong; Wang, Guochun; Wang, Jinping

    2013-02-01

    Type B insulin resistance syndrome is characterized by the formation of autoantibodies against insulin receptors, which can cause severe hyperglycemia and insulin resistance. Systemic lupus erythematosus is the most common underlying diseases of the syndrome. This report details our study of a case involving a Chinese female with type B insulin resistance syndrome as well as systemic lupus erythematosus who completely recovered after undergoing immunosuppressive therapy, specifically pulse therapy utilizing intravenous immunoglobulin. We also conducted search in MEDLINE and Chinese BioMedicine database to identify relevant literatures published in the past 46 years. From our searches, six case reports in Chinese, 15 case reports, and a 28-year perspective article in English met our criteria; a total of 67 cases were included in our report. The mean age of subjects at presentation for groups A, B, and C were 42.95, 44.10, and 41.68 years, respectively, yielding no significant difference between these groups. African Americans were the most susceptible group to type B insulin resistance syndrome, followed by Asians representing 20.90 % of all cases. Comparisons between the three main racial groups surveyed indicated that the mean age of subjects at presentation were very contiguous for African Americans and Asians, and mean age of white people was remarkably higher than either of the first two groups. The syndrome appeared most common among Asian males, and white males were relatively less likely to suffer from type B insulin resistance syndrome. Hypoglycemia was most commonly observed in white people than in other racial groups. Hypoalbuminemia, elevated serum immunoglobulin G, and elevated sedimentation rates were more common in African Americans; Asian cases were more likely to show low serum C3 or C4 and nephritis. Two cases received intravenous immunoglobulin therapy, which has a remarkably rapid effect on insulin resistance.

  12. Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D.

    PubMed

    Nunn, F; Cave, T A; Knottenbelt, C; Poxton, I R

    2004-07-24

    There is growing evidence that equine dysautonomia is a toxicoinfection with Clostridium botulinum type C. The possibility that feline dysautonomia has the same aetiology was investigated by attempting to detect botulinum type C neurotoxin in the food, faeces and the contents of the ileum of affected cats, and by serology. The toxin was detected directly in four of eight affected cats and after enrichment in seven of them, and in their dried food. No toxin was detected in healthy control cats or in their tinned food. Recent exposure to the organism was assessed by the detection of immunoglobulin A (IgA) in the faeces of healthy control cats and affected cats. The levels of IgA antibodies to the toxin and to surface antigens of C. botulinum type C in the faeces of the affected cats 14 weeks after the outbreak were significantly higher than in the faeces of the control cats.

  13. Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome.

    PubMed

    Zhao, Xiuli; Sun, Miao; Zhao, Jin; Leyva, J Alfonso; Zhu, Hongwen; Yang, Wei; Zeng, Xuan; Ao, Yang; Liu, Qing; Liu, Guoyang; Lo, Wilson H Y; Jabs, Ethylin Wang; Amzel, L Mario; Shan, Xiangnian; Zhang, Xue

    2007-02-01

    HOXD13, the homeobox-containing gene located at the most 5' end of the HOXD cluster, plays a critical role in limb development. It has been shown that mutations in human HOXD13 can give rise to limb malformations, with variable expressivity and a wide spectrum of clinical manifestations. Polyalanine expansions in HOXD13 cause synpolydactyly, whereas amino acid substitutions in the homeodomain are associated with brachydactyly types D and E. We describe two large Han Chinese families with different limb malformations, one with syndactyly type V and the other with limb features overlapping brachydactyly types A4, D, and E and mild syndactyly of toes 2 and 3. Two-point linkage analysis showed LOD scores >3 (theta =0) for markers within and/or flanking the HOXD13 locus in both families. In the family with syndactyly type V, we identified a missense mutation in the HOXD13 homeodomain, c.950A-->G (p.Q317R), which leads to substitution of the highly conserved glutamine that is important for DNA-binding specificity and affinity. In the family with complex brachydactyly and syndactyly, we detected a deletion of 21 bp in the imperfect GCN (where N denotes A, C, G, or T) triplet-containing exon 1 of HOXD13, which results in a polyalanine contraction of seven residues. Moreover, we found that the mutant HOXD13 with the p.Q317R substitution was unable to transactivate the human EPHA7 promoter. Molecular modeling data supported these experimental results. The calculated interactions energies were in agreement with the measured changes of the activity. Our data established the link between HOXD13 and two additional limb phenotypes--syndactyly type V and brachydactyly type A4--and demonstrated that a polyalanine contraction in HOXD13, most likely, led to other digital anomalies but not to synpolydactyly. We suggest the term "HOXD13 limb morphopathies" for the spectrum of limb disorders caused by HOXD13 mutations.

  14. Spontaneous common iliac arteries rupture in Ehlers-Danlos syndrome type IV: report of two cases and review of the literature.

    PubMed Central

    Habib, K.; Memon, M. A.; Reid, D. A.; Fairbrother, B. J.

    2001-01-01

    Two patients with previously undiagnosed Ehlers-Danlos syndrome type IV (EDS IV) presented acutely with clinical features suggestive of hypovolemic shock. Emergency laparotomies in both of them revealed spontaneous rupture of the common iliac arteries. The clinical features, operative findings, surgical approach, outcome and implications are discussed. Images Figure 1 Figure 2 Figure 3 PMID:11320937

  15. Measuring Regularity of Human Postural Sway Using Approximate Entropy and Sample Entropy in Patients with Ehlers-Danlos Syndrome Hypermobility Type

    ERIC Educational Resources Information Center

    Rigoldi, Chiara; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Mainardi, Luca; Galli, Manuela

    2013-01-01

    Ligament laxity in Ehlers-Danlos syndrome hypermobility type (EDS-HT) patients can influence the intrinsic information about posture and movement and can have a negative effect on the appropriateness of postural reactions. Several measures have been proposed in literature to describe the planar migration of CoP over the base of support, and the…

  16. Ketosis-prone type 2 diabetes mellitus in a patient with Sheehan's syndrome: a rare convergence of two distinct endocrine entities.

    PubMed

    Naha, Kushal; Vivek, G; Dasari, Sowjanya; Prabhu, Mukhyaprana

    2012-01-18

    A 36-year-old housewife, previously diagnosed with Sheehan's syndrome on glucocorticoid and thyroxine replacement therapy, presented with unprovoked diabetic ketoacidosis. Ketoacidosis was corrected with intravenous fluids and insulin therapy. Further evaluation was suggestive of type 2 diabetes mellitus. On follow-up, she experienced repeated episodes of hypoglycaemia and insulin was tapered and stopped. Adequate glycaemic control was maintained with metformin monotherapy.

  17. Tourette Syndrome

    MedlinePlus

    ... a person is concentrating (like working on a computer) or relaxing (like listening to music). The type ... doctor who knows a lot about the nervous system). All kids who have Tourette syndrome have tics — ...

  18. Metabolic syndrome

    MedlinePlus

    ... obesity ). This body type may be described as "apple-shaped." Insulin resistance. Insulin is a hormone produced ... Syndrome Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  19. False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?

    PubMed

    Homa, Katarzyna; Stefański, Adam; Zmysłowska, Agnieszka; Molęda, Piotr; Bryśkiewicz, Marta Ewa; Majkowska, Liliana

    2014-01-01

    Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.

  20. [Presence of enterotoxin C and toxic shock syndrome toxin--1 (TSST-1) genes in population of Staphylococcus aureus phage type 187].

    PubMed

    Garbacz, Katarzyna; Piechowicz, Lidia; Galiński, Janusz

    2006-01-01

    The aim of this study was to examine whether Staphylococcus aureus of phage type 187 possess the genes of enterotoxins and toxic shock syndrom toxin. Sixteen phage type 187 strains were isolated from the hospital patients (12) and the carriers (4) in twelve medical centres in Poland during 1991 and 2005. Biotyping, phage typing, antibiotic susceptibility, detection of the genes of enterotoxins (sea--sed) and toxic shock syndrome toxin (tst) was tested. The results of this study showed that all staphylococci of phage type 187 belonged to the human biotype (A) and appeared to be sensitive to all of the tested antibiotics, including methicillin (MSSA). Almost all of them (93.8%) had the enterotoxin C gene and TSST-1 gene. This fact allows to consider them the strains of potentially high virulence.

  1. A locus for Waardenburg syndrome type II maps to chromosome 1p13.3-2.1

    SciTech Connect

    Lalwani, A.K.; San Agustin, T.B.; Wilcox, E.R.

    1994-09-01

    Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes and distinctive facial features. WS type I (WS1) is characterized by a high frequency of dystopia canthorum whereas WS type II (WS2) individuals have normal inter canthal distances. Previous studies have shown that WS1 is caused by mutations in the PAX3 gene on chromosome 2q whereas WS2 is unlinked to PAX3. However, analyses of WS2 families have been complicated by the possibility of misdiagnosis of secondary cases with mild features of WS2. We initiated a genome search in 8 WS2 families. Suggestive evidence for linkage to D1S248 and AMY2B was found in one family (both markers: Z-max=2.4 at {Theta}=0), to D1S485 and D1S495 in a second family (both markers: Z-max=2.2 at {Theta}=0), and to D1S248 in a third family (Z-max=1.1 at {Theta}=.11). WS2 was not linked to any of these markers in the total group of families. Location scores for each family were calculated by a six-locus analysis using the marker map AMY2B/D1S486 - .03 - D1S495 - .02 - D1S248 - .05 - D1S457 - .04 - D1S250. Assessment of these scores for linkage and heterogeneity using the admixture test revealed significant evidence for linkage (P<.0001) under the assumption of heterogeneity ({alpha}=.40). The most likely location for WS2 is at D1S495, although either of the intervals flanking this marker may contain the mutant gene. All other locations were ruled out with odds of greater than l00 to 1. Our findings suggest that there are at least two loci for WS type II. Complementary crossovers in the linked families make feasible attempts to narrow the location of the WS2 gene by positional cloning. Analyses of additional families will be needed to estimate more precisely the proportion of linked families and identify the gene.

  2. Embryonic type Na+ channel β-subunit, SCN3B masks the disease phenotype of Brugada syndrome

    PubMed Central

    Okata, Shinichiro; Yuasa, Shinsuke; Suzuki, Tomoyuki; Ito, Shogo; Makita, Naomasa; Yoshida, Tetsu; Li, Min; Kurokawa, Junko; Seki, Tomohisa; Egashira, Toru; Aizawa, Yoshiyasu; Kodaira, Masaki; Motoda, Chikaaki; Yozu, Gakuto; Shimojima, Masaya; Hayashiji, Nozomi; Hashimoto, Hisayuki; Kuroda, Yusuke; Tanaka, Atsushi; Murata, Mitsushige; Aiba, Takeshi; Shimizu, Wataru; Horie, Minoru; Kamiya, Kaichiro; Furukawa, Tetsushi; Fukuda, Keiichi

    2016-01-01

    SCN5A is abundant in heart and has a major role in INa. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each β-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that INa of mutated SCN5A is decreased and SCN3B augmented INa of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties. PMID:27677334

  3. Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction.

    PubMed

    Malan, Daniela; Zhang, Miao; Stallmeyer, Birgit; Müller, Jovanca; Fleischmann, Bernd K; Schulze-Bahr, Eric; Sasse, Philipp; Greber, Boris

    2016-03-01

    Long QT syndrome is a potentially life-threatening disease characterized by delayed repolarization of cardiomyocytes, QT interval prolongation in the electrocardiogram, and a high risk for sudden cardiac death caused by ventricular arrhythmia. The genetic type 3 of this syndrome (LQT3) is caused by gain-of-function mutations in the SCN5A cardiac sodium channel gene which mediates the fast Nav1.5 current during action potential initiation. Here, we report the analysis of LQT3 human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These were generated from a patient with a heterozygous p.R1644H mutation in SCN5A known to interfere with fast channel inactivation. LQT3 hiPSC-CMs recapitulated pathognomonic electrophysiological features of the disease, such as an accelerated recovery from inactivation of sodium currents as well as action potential prolongation, especially at low stimulation rates. In addition, unlike previously described LQT3 hiPSC models, we observed a high incidence of early after depolarizations (EADs) which is a trigger mechanism for arrhythmia in LQT3. Administration of specific sodium channel inhibitors was found to shorten action and field potential durations specifically in LQT3 hiPSC-CMs and antagonized EADs in a dose-dependent manner. These findings were in full agreement with the pharmacological response profile of the underlying patient and of other patients from the same family. Thus, our data demonstrate the utility of patient-specific LQT3 hiPSCs for assessing pharmacological responses to putative drugs and for improving treatment efficacies.

  4. Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

    PubMed Central

    Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

    2013-01-01

    Objectives Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design Prospective analysis. Patients 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype–phenotype analyses. Setting All analyses were performed in a large German laboratory specialised in genetic diagnostics. Results 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. Conclusions On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype–phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum

  5. Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

    PubMed

    Roy, Snigdha; Watkins, Nick; Heck, Detlef

    2012-01-01

    Fragile X syndrome (FXS) is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1) gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT) littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

  6. MAP1LC3B overexpression protects against Hermansky-Pudlak syndrome type-1-induced defective autophagy in vitro

    PubMed Central

    Ahuja, Saket; Knudsen, Lars; Chillappagari, Shashi; Henneke, Ingrid; Ruppert, Clemens; Korfei, Martina; Gochuico, Bernadette R.; Bellusci, Saverio; Seeger, Werner; Ochs, Matthias; Mahavadi, Poornima

    2015-01-01

    Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, and some patients with HPS develop pulmonary fibrosis, known as HPS-associated interstitial pneumonia (HPSIP). We have previously reported that HPSIP is associated with severe surfactant accumulation, lysosomal stress, and alveolar epithelial cell type II (AECII) apoptosis. Here, we hypothesized that defective autophagy might result in excessive lysosomal stress in HPSIP. Key autophagy proteins, including LC3B lipidation and p62, were increased in HPS1/2 mice lungs. Electron microscopy demonstrated a preferable binding of LC3B to the interior of lamellar bodies in the AECII of HPS1/2 mice, whereas in wild-type mice it was present on the limiting membrane in addition to the interior of the lamellar bodies. Similar observations were noted in human HPS1 lung sections. In vitro knockdown of HPS1 revealed increased LC3B lipidation and p62 accumulation, associated with an increase in proapoptotic caspases. Overexpression of LC3B decreased the HPS1 knockdown-induced p62 accumulation, whereas rapamycin treatment did not show the same effect. We conclude that loss of HPS1 protein results in impaired autophagy that is restored by exogenous LC3B and that defective autophagy might therefore play a critical role in the development and progression of HPSIP. PMID:26719147

  7. MAP1LC3B overexpression protects against Hermansky-Pudlak syndrome type-1-induced defective autophagy in vitro.

    PubMed

    Ahuja, Saket; Knudsen, Lars; Chillappagari, Shashi; Henneke, Ingrid; Ruppert, Clemens; Korfei, Martina; Gochuico, Bernadette R; Bellusci, Saverio; Seeger, Werner; Ochs, Matthias; Guenther, Andreas; Mahavadi, Poornima

    2016-03-15

    Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, and some patients with HPS develop pulmonary fibrosis, known as HPS-associated interstitial pneumonia (HPSIP). We have previously reported that HPSIP is associated with severe surfactant accumulation, lysosomal stress, and alveolar epithelial cell type II (AECII) apoptosis. Here, we hypothesized that defective autophagy might result in excessive lysosomal stress in HPSIP. Key autophagy proteins, including LC3B lipidation and p62, were increased in HPS1/2 mice lungs. Electron microscopy demonstrated a preferable binding of LC3B to the interior of lamellar bodies in the AECII of HPS1/2 mice, whereas in wild-type mice it was present on the limiting membrane in addition to the interior of the lamellar bodies. Similar observations were noted in human HPS1 lung sections. In vitro knockdown of HPS1 revealed increased LC3B lipidation and p62 accumulation, associated with an increase in proapoptotic caspases. Overexpression of LC3B decreased the HPS1 knockdown-induced p62 accumulation, whereas rapamycin treatment did not show the same effect. We conclude that loss of HPS1 protein results in impaired autophagy that is restored by exogenous LC3B and that defective autophagy might therefore play a critical role in the development and progression of HPSIP.

  8. Physiologic, metabolic, and muscle fiber type characteristics of musculus uvulae in sleep apnea hypopnea syndrome and in snorers.

    PubMed Central

    Sériès, F; Côté, C; Simoneau, J A; Gélinas, Y; St Pierre, S; Leclerc, J; Ferland, R; Marc, I

    1995-01-01

    Upper airway dilator muscles play an important role in the pathophysiology of sleep apnea hypopnea syndrome (SAHS). The mechanical and structural characteristics of these muscles remain unknown. The aim of this study was to compare the physiologic, metabolic, and fiber type characteristics of one upper airway dilator muscle (musculus uvulae, MU) in 11 SAHS and in seven nonapneic snorers. The different analyses were done on MU obtained during uvulo-palato-pharyngoplasty. Snorers and SAHS differed only in their apnea + hypopnea indices (11.5 +/- 5.9 and 34.2 +/- 14.6/h, respectively, mean +/- SD). Absolute twitch and tetanic tension production of MU was significantly greater in SAHS than in snorers while the fatigability index was similar in the two groups. Protein content and anaerobic enzyme activities of MU were significantly greater in SAHS than in snorers; no difference was observed for aerobic enzyme activities. The total muscle fiber cross-sectional area of MU was significantly higher in SAHS (2.2 +/- 0.9 mm2) than in snorers (1.1 +/- 0.7 mm2). The surface occupied by type IIA muscle fibers of MU was larger in SAHS (2.00 +/- 0.96) than in snorers (0.84 +/- 0.63 mm2). We conclude that the capacity for tension production and the anaerobic metabolic activity of MU are greater in SAHS than in snorers. PMID:7814616

  9. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro

    PubMed Central

    Li, Shilin; Jiao, Baihai; Wu, Jianqin; Zeng, Peibin; Chen, Limin

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance. PMID:28234991

  10. Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice.

    PubMed

    Heldermon, C D; Qin, E Y; Ohlemiller, K K; Herzog, E D; Brown, J R; Vogler, C; Hou, W; Orrock, J L; Crawford, B E; Sands, M S

    2013-09-01

    Mucopolysaccharidosis type IIIB (MPS IIIB) or Sanfilippo Syndrome type B is a lysosomal storage disease resulting from the deficiency of N-acetyl glucosaminidase (NAGLU) activity. We previously showed that intracranial adeno-associated virus (AAV)-based gene therapy results in partial improvements of several aspects of the disease. In an attempt to further correct the disease, MPS IIIB mice were treated at 2-4 days of age with intracranial AAV2/5-NAGLU (IC-AAV), intravenous lentiviral-NAGLU (IV-LENTI) or the combination of both (BOTH). The BOTH group had the most complete biochemical and histological improvements of any treatment group. Compared with untreated MPS IIIB animals, all treatments resulted in significant improvements in motor function (rotarod) and hearing (auditory-evoked brainstem response). In addition, each treatment group had a significantly increased median life span compared with the untreated group (322 days). The combination arm had the greatest increase (612 days), followed by IC-AAV (463 days) and IV-LENTI (358 days). Finally, the BOTH group had nearly normal circadian rhythm measures with improvement in time to activity onset. In summary, targeting both the systemic and central nervous system disease of MPS IIIB early in life appears to be the most efficacious approach for this inherited metabolic disorder.

  11. The influence of carbohydrate quality on cardiovascular disease, the metabolic syndrome, type 2 diabetes, and obesity - an overview.

    PubMed

    Slyper, Arnold H

    2013-01-01

    There is compelling evidence that carbohydrate quality has important influences on cardiovascular disease, the metabolic syndrome, type 2 diabetes, and obesity. Cohort and interventional studies indicate that dietary fiber is an important determinant of satiation, satiety, and weight gain, and also protects against cardiovascular disease. Cohort studies have shown that vegetables and fruits protect against coronary heart disease, whereas whole grains provide protection against cardiovascular disease, type 2 diabetes, and weight gain. Dietary glycemia within the range eaten by most of the population seems not to have a significant influence on body weight, although it may influence waist circumference. There is strong evidence from interventional trials that dietary glycemia does influence insulin resistance and diabetes control. Moreover, replacing saturated fat with high-glycemic carbohydrate may increase cardiovascular risk. Soft drink consumption is a proven cause of weight gain, which may relate to the lack of satiation provided by these drinks. In large amounts, dietary fructose leads to greater adverse metabolic changes than equivalent amounts of glucose, although the extent to which fructose per se is contributing to many of the metabolic changes found in the obese, as distinct from the calories it provides, is still a matter of debate.

  12. Portal-systemic encephalopathy after Fontan-type operation in patient with polysplenia syndrome.

    PubMed

    Koteda, Yusuke; Suda, Kenji; Kishimoto, Shintaro; Iemura, Motofumi

    2009-06-01

    An 18-year-old patient, who had polysplenia and single ventricle, presented with altered mental status 9 years after a Fontan-type operation and pacemaker implantation. He underwent replacement of common atrioventricular valve and aortic valve plasty 1 year previously and has been placed on multiple medications including beta-blocker for his poor ventricular function. Blood chemistry revealed hyperammonemia of 2420 microg/l as a cause of this altered mental status disturbance. Superior mesenteric arteriography revealed large portal-systemic shunts in venous phase as a cause of hyperammonemia. To control blood ammonia level, we placed him on low protein diet, oral polymixin B, and lactulose instead of closing shunt with device. This case illustrates that portal-systemic shunt may result in hyperammonemia leading to altered mental status long after a Fontan-type operation.

  13. Evaluation of a Botulinum Toxoid, Type B, for the Prevention of Shaker Foal Syndrome,

    DTIC Science & Technology

    1981-11-06

    standard mouse bioassay was used to determine the type B botulinum toxin netstralizing titer of colostrum , and sera (mares and foals). Each immunized...mareiseroconverted before foaling. On the day of foaling, broodmare colostrum tit’ rs exceeded serum titers by 3-15 fold. Toxin neutralizing activity was...and 42 days after birthi, suggesting strongly a rapid passil acquisition of antibodies via the colostrum .’-JSFS did not occur in foals of immunized

  14. [Unsuspected bronchial carcinoid tumor detected in a somatostatin receptor scintigraphy in a patient with multiple endocrine neoplasia syndrome type 1 and hypergastrinemia].

    PubMed

    Marín-Oyaga, V; Tirado-Hospital, J L; Cuenca-Cuenca, J I; Guerrero-Vázquez, R; Luján-Rodríguez, D; Vázquez-Albertino, R

    2013-03-01

    Multiple Endocrine Neoplasia type 1 syndrome (MEN1) is characterized by the presence of tumors in parathyroid glands, anterior pituitary gland, endocrine pancreas and duodenum. However, other tumors may also occur. One of them is the carcinoid tumor, which in this context, is more common in the gastrointestinal tract. Less common is the presence of carcinoid tumors of bronchial origin, which with histologic confirmation, may occur in 5-8% of cases and that appears more frequently in patients with hypergastrinemia. We report a patient with MEN1 syndrome, hypergastrinemia and an incidental finding in a somatostatin receptor scintigraphy of an unsuspected bronchial carcinoid tumor that was confirmed histologically.

  15. A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3.

    PubMed

    Pierpont, J W; St Jacques, D; Seaver, L H; Erickson, R P

    1995-03-01

    An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip (palate).

  16. Lemierre's syndrome presenting to the ED: rapidly fatal sepsis caused by methicillin-susceptible Staphylococcus aureus Staphylococcus protein A type t044.

    PubMed

    Pitsiou, Georgia; Kachrimanidou, Melina; Papa, Anna; Kioumis, Ioannis; Paspala, Asimina; Boutou, Afroditi; Vlachou, Stamatina; Tsorlini, Eleni; Argyropoulou-Pataka, Paraskevi

    2013-01-01

    We describe the case of a fatal septic illness in a previously healthy young man caused by community-acquired methicillin-susceptible Staphylococcus aureus of Staphylococcus protein A (spa) type t044. The patient developed a devastating Lemierre-like syndrome with extensive thrombosis of inferior vena cava and iliac veins with multiple metastatic septic emboli of the lungs. He presented to the emergency department with rapidly progressing sepsis followed by multiple organ dysfunction syndrome. Recognition of such virulent community-acquired strains is of great importance because they could prove to be emerging pathogens for life-threatening diseases.

  17. Epigenetic regulation of TGF-β1 signalling in dilative aortopathy of the thoracic ascending aorta.

    PubMed

    Forte, Amalia; Galderisi, Umberto; Cipollaro, Marilena; De Feo, Marisa; Della Corte, Alessandro

    2016-08-01

    The term 'epigenetics' refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor β1 (TGF-β1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-β1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-β1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys-Dietz and Marfan's syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-β1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5-2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-β1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies.

  18. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis

    PubMed Central

    Zhang, Pei; Huang, Angela; Morales-Ruiz, Manuel; Starcher, Barry C.; Huang, Yan; Sessa, William C.; Niklason, Laura E.

    2012-01-01

    Abstract Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibility of using engineered zinc-finger protein transcription factors (ZFPs) to achieve compensatory expression of haploinsufficient genes by inducing augmented expression from the remaining wild-type allele. For complex genes with multiple splice variants, this approach could have distinct advantages over cDNA-based gene replacement strategies. Targeting the elastin gene, we show that transcriptional activation by engineered ZFPs can induce compensatory expression from the wild-type allele in the setting of classic WBS and SVAS genetic mutations, increase elastin expression in wild-type cells, induce expression of the major elastin splice variants, and recapitulate their natural stoichiometry. Further, we establish that transcriptional activation of the mutant allele in SVAS does not overcome nonsense-mediated decay, and thus ZFP-mediated transcriptional activation is not likely to indu