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Sample records for brachmann-de lange syndrome

  1. Brachmann-de Lange syndrome

    SciTech Connect

    Ackerman, J.; Gilbert-Barness, E.

    1997-01-31

    This report describes an infant with Brachmann-de Lange syndrome and the diagnosis of this disease in utero. It also discusses the future ability to rely on chromosome 9-associated levels of pregnancy-associated plasma protein A (PAPPA) as an indicator of the disease, rather than solely relying on the phenotype of the fetus as determined during ultrasound. 3 refs., 2 figs.

  2. [Auditory function in children with Brachmann-de Lange syndrom].

    PubMed

    Kozłowski, Jacek; Wierzba, Jolanta; Narozny, Waldemar; Balcerska, Anna; Stankiewicz, Czesław; Kuczkowski, Jerzy

    2006-01-01

    The aim of the research work is the evaluation of auditory function in children with rare, genetically determined Brachmann-de Lange syndrome. Test material came from 18 children (7 girls and 11 boys) between 11 months and 18 years of age with Brachmann-de Lange syndrome who have been diagnosed and treated at ENT Department and Department of Paediatrics, Haematology, Oncology and Endocrinology Medical University of Gdansk with support of Cornelia de Lange Association - Poland. In all children examinations of brainstem auditory evoked potential have been carried out as well as tympanometric examination in case of finding hearing loss. All these examinations were carried out in ENT Department of Medical University of Gdansk, using Racia-Alvar Centor C apparatus and Madsen-Zodiak 901. 9 (50%) of patients demonstrated hearing loss. In 3 (16.7%) cases the conduction hearing loss was connected with the chronic diseases of middle ear which required medical treatment. In remaining 6 (33.3%) cases due to sensorineural hearing loss children had hearing aids applied and underwent rehabilitation. The results indicate that all children with Brachmann-de Lange syndrome should undergo examinations of brainstem auditory evoked potential. It enables to detect hypoacusis and initiate proper treatment. Lack of the opportunity of having a hearing aid applied and further rehabilitation deepens the social isolation of the little patients and inhibits their natural progress in communication. In such cases mental retardation may subsequently occur.

  3. Autosomal dominant inheritance of Brachmann-de Lange syndrome

    SciTech Connect

    Kozma, C.

    1996-12-30

    A mother with mild phenotype and her severely affected son, both with classic manifestations of Brachmann-de Lange syndrome (BDLS), are described. This documented mother-to-child transmission supports the hypothesis of autosomal dominant transmission with intrafamilial variability. Known cases of BDLS with autosomal dominant inheritance are reviewed. Although most cases of BDLS are sporadic, a careful evaluation of parents of affected children is important for appropriate genetic counseling. 15 refs., 3 figs., 1 tab.

  4. Brachmann-de Lange syndrome: Autosomal dominant inheritance and male-to-male transmission

    SciTech Connect

    McKenney, R.R.; Elder, F.F.B.; Northrup, H.; Garcia, J.

    1996-12-30

    We report on familial occurrence of the Brachmann-de Lange syndrome (BDLS): a mildly affected father and his severely affected son and daughter who have different mothers. Both children are severely affected while the father has a much milder but definite BDLS phenotype. Our report documents the third example of male-to-male transmission and adds to the argument against exclusively maternal transmission in familial cases. In addition, our findings illustrate the occurrence of severe manifestations in cases of familial BDLS. 29 refs., 3 figs.

  5. Identical twin discordance for the Brachmann-de Lange syndrome revisited

    SciTech Connect

    Carakushansky, G.; Goncalves, M.R.; Kahn, E.

    1996-06-14

    The only known twin pair evidently discordantly affected for the BDLS (Brachmann-de Lange syndrome) and who had been considered monozygotic (MZ) based on blood analysis remained a problem because biological zygosity determination needed further typing. In this report we review the clinical findings of this pair of twins at the age of 20. The use of DNA fingerprinting with three multilocus probes, F10, DNT24, and 33.6, allowed us to present evidence of monozygosity with a high degree of certainty. The significance of this confirmation of discordance in determining the cause of BDLS is discussed. Intensive comparative genomic studies of the discordant twin sisters may be useful to unravel the molecular genetics of this enigmatic pattern of malformation. 21 refs., 2 figs.

  6. Multiple mitochondrial DNA deletions and persistent hyperthermia in a patient with Brachmann-de Lange phenotype

    SciTech Connect

    Melegh, B.; Bock, I.; Mehes, K.

    1996-10-02

    In a newborn boy with characteristics of Brachmann-de Lange syndrome (BDLS), high temperatures were observed on the second day after birth and recurred 2-6 times daily during the 7 months of the patient`s life. After, transient hypertonia hypotonia developed. In muscle biopsy specimen taken on the 51st day of life, serious and progressive distortion of mitochondria was observed. In several mitochondria the cristae structure was broken, other mitochondria were shrunken and the damage progressed towards further deterioration in other organelles. At several points between the myofibrils, amorphous material was seen, possibly debris of destroyed mitochondria. Most myofibrils seemed to be intact; however, in some areas myolytic signs were present. Analysis of the mitochondrial DNA (mtDNA) showed multiple deletions in skeletal and heart muscles, liver, lung and kidney. Since the mtDNA encodes several proteins of the respiratory complexes, the deleted mtDNA certainly affected the integrity of the mitochondrial oxidative phosphorylation process by synthesis of abnormal proteins. In the present case the hyperthermia may have been a result of the mtDNA damage. 13 refs.

  7. [Systemic and ophthalmological findings in Cornelia de Lange syndrome].

    PubMed

    Mrugacz, Małgorzata; Sielicka, Danuta

    2012-01-01

    Cornelia de Lange Syndrome (CdLS, de Lange syndrome, Brachmann-de Lange syndrome), is a relatively rare genetic disorder, characterized by set of clinical abnormalities concerning different organs and systems. Phenotypic diagnosis is based on a specific dysmorphic features seen after the birth. We described a genetic basis, hereditary patterns, characteristic dysmorphic features and the most common clinical findings of patients Cornelia de Lange Syndrome concerning eye and vision, hearing, cardiovascular, respiratory, gastrointestinal, genitourinary, skeletal and psychomotor development.

  8. Interdisciplinary therapy in Cornelia de Lange syndrome - review of the literature.

    PubMed

    Mikołajewska, Emilia

    2013-01-01

    Cornelia de Lange syndrome (CdLS, also called Brachmann-de Lange syndrome - BdLS) is a multisystem developmental disorder characterized by distinctive facial features, growth and mental retardation, microcephaly, and various malformations. According to their clinical status, patients with CdLS require individual interdisciplinary therapy. The therapy is difficult and mainly symptomatic. To optimize the therapy results, early diagnosis programs and appropriate developmental and therapeutic intervention are recommended. The interdisciplinary approach described in the article needs further clinical research and detailed guidelines.

  9. Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature.

    PubMed

    Shenoy, Bhamy Hariprasad; Gupta, Amit; Sachdeva, Virender; Kekunnaya, Ramesh

    2014-05-01

    Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, ophthalmological abnormalities, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. Most common and consistent ophthalmic features reported are nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis, synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring, and myopia. In this report we report a case of a 5-year old boy who presented to our institution with complaint of blurring of vision in the right eye since birth. A diagnosis of Cornelia de Lange syndrome was arrived at based on the characteristic external and ophthalmic examination. He was found to have a rare association of optic nerve head coloboma in the right eye and a novel finding of an optic disk pit in the left eye. The association of optic disk pit with CdLS has never been reported earlier. We aim to provide a thorough review of literature of this not so uncommon syndrome.

  10. Cornelia de lange syndrome

    PubMed Central

    Tayebi, Naeimeh

    2008-01-01

    BACKGROUND: Cornelia de Lange syndrome (CDLS) is a rare multiple congenital anomaly syndrome characterized by a distinctive facial appearance, developmental delay, growth retardation, low birth weight, skeletal formation anomaly, and hirsutism. CASE: Here for the first time a case of CDLS from Iran, a 15-week-old male infant who was refereed as a case of multiple congenital anomalies. Clinical investigation showed that the child was a case of CDLS. CONCLUSION: This is the first case report with CDLS in Iran. PMID:20300288

  11. Genetics Home Reference: Cornelia de Lange syndrome

    MedlinePlus

    ... autism, a developmental condition that affects communication and social interaction. Additional signs and symptoms of Cornelia de Lange ... de Lange Syndrome (CdLS) Genetics Education Materials for School Success (GEMSS) MalaCards: cornelia de lange syndrome 1 ...

  12. Cornelia de Lange syndrome.

    PubMed

    Liu, Jinglan; Baynam, Gareth

    2010-01-01

    Cornelia de Lange syndrome (CdLS) (OMIM # 122470, #300590 and #610759) is an autosomal dominant disorder that is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Heterozygous mutations in the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and SMC3, have been identified in approximately 65% of individuals with CdLS. Cohesin regulates sister chromatid cohesion during the mitotis and meiosis. In addition, cohesin has been demonstrated to play a critical role in the regulation of gene expression. Furthermore, multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double strand DNA break repair, chromatin remodeling and maintaining genomic stability. Here, we will discuss the biology ofcohesin and its associated factors, with emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS related proteins.

  13. Cornelia de lange syndrome with thyroid agenesis of an indonesian patient.

    PubMed

    Maskoen, A M; Laksono, B; Hajjah, R; Zada, A; Suciati, L P; Fauziah, P N; Nataprawira, H M

    2017-08-30

    Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities. The prevalence ranges from 1:100,000 to as high as 1:10,000. Most cases (50-60%) were carried mutation in NIPBL gene. To our knowledge this is the first CdLs Indonesian case that reported with molecular analysis study. We present an 11 months old female Indonesian patient with classic CdLs with congenital hypothyroid. Genetics studies were performed in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Thyroid studies (T3, T4, TSH and thyroid scan) were performed. Low level of T3 and T4, and high level of TSH were observed. Thyroid agenesis was found in thyroid scan examination. We detected thyroid agenesis which has been never reported in CdLs patients. We could not find any mutation in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Further genetics examinations were necessary whether there is mutation in other locus.

  14. Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

    PubMed Central

    Braunholz, Diana; Hullings, Melanie; Gil-Rodríguez, María Concepcion; Fincher, Christopher T; Mallozzi, Mark B; Loy, Elizabeth; Albrecht, Melanie; Kaur, Maninder; Limon, Janusz; Rampuria, Abhinav; Clark, Dinah; Kline, Antonie; Dalski, Andreas; Eckhold, Juliane; Tzschach, Andreas; Hennekam, Raoul; Gillessen-Kaesbach, Gabriele; Wierzba, Jolanta; Krantz, Ian D; Deardorff, Matthew A; Kaiser, Frank J

    2012-01-01

    Cornelia de Lange syndrome (CdLS; or Brachmann-de Lange syndrome) is a dominantly inherited congenital malformation disorder with features that include characteristic facies, cognitive delays, growth retardation and limb anomalies. Mutations in nearly 60% of CdLS patients have been identified in NIPBL, which encodes a regulator of the sister chromatid cohesion complex. NIPBL, also known as delangin, is a homolog of yeast and amphibian Scc2 and C. elegans PQN-85. Although the exact mechanism of NIPBL function in sister chromatid cohesion is unclear, in vivo yeast and C. elegans experiments and in vitro vertebrate cell experiments have demonstrated that NIPBL/Scc2 functionally interacts with the MAU2/Scc4 protein to initiate loading of cohesin onto chromatin. To test the significance of this model in the clinical setting of CdLS, we fine-mapped the NIBPL–MAU2 interaction domain and tested the functional significance of missense mutations and variants in NIPBL and MAU2 identified in these minimal domains in a cohort of patients with CdLS. We demonstrate that specific novel mutations at the N-terminus of the MAU2-interacting domain of NIBPL result in markedly reduced MAU2 binding, although we appreciate no consistent clinical difference in the small group of patients with these mutations. These data suggest that factors in addition to MAU2 are essential in determining the clinical features and severity of CdLS. PMID:21934712

  15. Cornelia de Lange syndrome.

    PubMed

    Boyle, M I; Jespersgaard, C; Brøndum-Nielsen, K; Bisgaard, A-M; Tümer, Z

    2015-07-01

    Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Otolaryngological presentations of Cornelia de Lange syndrome.

    PubMed

    Hamilton, Jane; Clement, W Andrew; Kubba, Haytham

    2014-09-01

    Children with Cornelia de Lange syndrome frequently present to otolaryngology services with hearing problems. Airway problems have not previously been reported. We wish to describe our experience of the overall management in a series of children with Cornelia de Lange syndrome. Retrospective case note review of children diagnosed with Cornelia de Lange syndrome presenting to our department between 2005 and 2014. Six patients were seen. Airway problems consisted of laryngeal overspill with severe gastroesophageal dysmotility and reflux despite structurally normal airway (1 case), laryngomalacia requiring supraglottoplasty (2 cases), reflux laryngitis with secondary laryngomalacia and coincidental tracheal diverticulum (1 case) choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1 case). Supraglottoplasty produced a dramatic improvement in feeding and breathing in both children who underwent the procedure. Two children had palatal anomalies and one underwent cochlear implantation for a profound sensorineural hearing loss. Children with Cornelia de Lange syndrome have multifaceted ENT problems. Airway pathology has not previously been described in Cornelia de Lange syndrome but has been common in our experience. We wish to highlight that laryngomalacia in Cornelia de Lange syndrome responds well to supraglottoplasty. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Dental findings in Cornelia de Lange syndrome.

    PubMed

    Toker, Aslihan Soyal; Ay, Sinan; Yeler, Hasan; Sezgin, Ilhan

    2009-04-30

    Cornelia de Lange syndrome is a congenital disease, basically characterized by psychomotor retardation associated with a series of malformations, including mainly skeletal, craniofacial deformities together with gastrointestinal and cardiac malformations. There is no definitive biochemical or chromosomal marker for the prenatal diagnosis of this syndrome. We actually want to present the case of a 10-year-old patient, who was admitted to our clinic for dental pain. The patient had the symptoms of Cornelia de Lange syndrome. During the oral examination of this patient, the patient was found to have the typical symptoms of Cornelia de Lange syndrome, such as micrognathia and delayed eruption in conjunction with the symptoms of the Hutchinson's syndrome, which had never been reported before.

  18. Cornelia de Lange Syndrome Foundation

    MedlinePlus

    ... Volunteer Recognition de Lange Society Donate Now Donation Options Celebration and Memorial Gifts Planned Giving Monthly Giving Corporate Partnership Matching Gifts Stocks, Trusts and Other Gifts 21st Century Conference Fund ...

  19. ABR Audiometry in Cornelia De Lange Syndrome.

    ERIC Educational Resources Information Center

    Brown, Denice P.

    Eight children (ages 13 days to 5 years) with a diagnosis of Cornelia de Lange syndrome received audiologic evaluation consisting of immittance audiometry and auditory brainstem response audiometry to air and bone conducted "click" stimuli, as behavioral testing was unreliable due to patient age and/or developmental delay. Developmental…

  20. ABR Audiometry in Cornelia De Lange Syndrome.

    ERIC Educational Resources Information Center

    Brown, Denice P.

    Eight children (ages 13 days to 5 years) with a diagnosis of Cornelia de Lange syndrome received audiologic evaluation consisting of immittance audiometry and auditory brainstem response audiometry to air and bone conducted "click" stimuli, as behavioral testing was unreliable due to patient age and/or developmental delay. Developmental…

  1. Social Anxiety in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Richards, Caroline; Moss, Jo; O'Farrell, Laura; Kaur, Gurmeash; Oliver, Chris

    2009-01-01

    In this study we assessed the behavioral presentation of social anxiety in Cornelia de Lange syndrome (CdLS) using a contrast group of Cri du Chat syndrome (CdCS). Behaviors indicative of social anxiety were recorded in twelve children with CdLS (mean age = 11.00; SD = 5.15) and twelve children with CdCS (8.20; SD = 2.86) during social…

  2. Social Anxiety in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Richards, Caroline; Moss, Jo; O'Farrell, Laura; Kaur, Gurmeash; Oliver, Chris

    2009-01-01

    In this study we assessed the behavioral presentation of social anxiety in Cornelia de Lange syndrome (CdLS) using a contrast group of Cri du Chat syndrome (CdCS). Behaviors indicative of social anxiety were recorded in twelve children with CdLS (mean age = 11.00; SD = 5.15) and twelve children with CdCS (8.20; SD = 2.86) during social…

  3. Neuroimaging features of Cornelia de Lange syndrome.

    PubMed

    Whitehead, Matthew T; Nagaraj, Usha D; Pearl, Phillip L

    2015-07-01

    Cornelia de Lange syndrome is a rare genetic disease characterized by distinctive facial dysmorphia and dwarfism. Multiple organ system involvement is typical. Various central nervous system (CNS) aberrations have been described in the pathology literature; however, the spectrum of neuroimaging manifestations is less well documented. To present neuroimaging findings from a series of eight patients with Cornelia de Lange syndrome. The CT/MR database at a single academic children's hospital was searched for the terms "Cornelia," "Brachmann" and "de Lange." The search yielded 18 exams from 16 patients. Two non-CNS and six exams without available images were excluded. Ten exams from eight patients were evaluated by a board-certified neuroradiologist. All patients had skull base dysplasia, most with an unusual coronal basioccipital cleft (7/8). All brain MR exams showed microcephaly, volume loss and gyral simplification (5/5). Six patients had an absent massa intermedia. Four patients had small globe anterior segments; three had optic pathway hypoplasia. Basilar artery fenestration was present in two patients; vertebrobasilar hypoplasia was present in one patient. The inner ear vestibules were dysplastic in two patients. One patient had pachymeningeal thickening. Spinal anomalies included scoliosis, segmentation anomalies, endplate irregularities, basilar invagination, foramen magnum stenosis and tethered spinal cord. Typical imaging manifestations of Cornelia de Lange syndrome include skull base dysplasia with coronal clival cleft, cerebral and brainstem volume loss, and gyral simplification. Membranous labyrinth dysplasia, anterior segment and optic pathway hypoplasia, basilar artery fenestration, absent massa intermedia and spinal anomalies may also be present.

  4. De Lange Syndrome: Report of 20 Cases

    PubMed Central

    McArthur, R. G.; Edwards, J. H.

    1967-01-01

    Typus Degenerativus Amstelodamensis or Amsterdam dwarfism, a syndrome of unknown etiology characterized by mental retardation, a distinctive face, characteristic hands and feet, defective growth and other minor malformations, was first described by Cornelia de Lange in 1933. Approximately 69 cases, including nine autopsies, have been reported in the literature. In this paper we present a further 20, with illustrations of the syndrome from infancy to puberty (including de Lange's original three cases). The historical, physical, laboratory and radiographic findings of de Lange's three patients and our 20 are tabulated. Autopsy findings in one of our patients are reported and the literature is briefly reviewed. Although some observers have recently reported chromosome abnormalities in de Lange's syndrome, we feel that the diagnosis is made from the history and physical examination and that there are no definitive laboratory aids which can confirm the diagnosis. Chromosome studies in all 20 of our patients were normal and the genetic implications are discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 9Fig. 11p1197-a PMID:6022788

  5. Case Report: Atypical Cornelia de Lange Syndrome

    PubMed Central

    Leanza, Vito; Rubbino, Gabriella; Leanza, Gianluca

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID:26834972

  6. Genetics Home Reference: Jervell and Lange-Nielsen syndrome

    MedlinePlus

    ... KCNQ1 or KCNE1 mutation have a long QT interval with related heart abnormalities, but their hearing is ... disease Jervell-Lange Nielsen syndrome JLNS prolonged QT interval in EKG and sudden death surdo-cardiac syndrome ...

  7. Cornelia de Lange Syndrome: Evolution of the Phenotype

    ERIC Educational Resources Information Center

    Passarge, Eberhard; And Others

    1971-01-01

    The medical case history of a 2-year-old girl who developed, during the second year of life, the classical phenotype (typical appearance) indicative of the deLange syndrome, with both mental and physical impairment. (KW)

  8. Cornelia de Lange Syndrome: Evolution of the Phenotype

    ERIC Educational Resources Information Center

    Passarge, Eberhard; And Others

    1971-01-01

    The medical case history of a 2-year-old girl who developed, during the second year of life, the classical phenotype (typical appearance) indicative of the deLange syndrome, with both mental and physical impairment. (KW)

  9. Immunologic features of Cornelia de Lange syndrome.

    PubMed

    Jyonouchi, Soma; Orange, Jordan; Sullivan, Kathleen E; Krantz, Ian; Deardorff, Matthew

    2013-08-01

    Cornelia de Lange syndrome (CdLS) is a genetic syndrome with multisystem abnormalities. Infections are a significant cause of morbidity and mortality. The goals of our study were to identify the frequency and types of infections in CdLS and to determine if underlying immunodeficiency contributes to the clinical spectrum of this syndrome. We assessed infectious histories in 45 patients with CdLS and evaluated conventional immunologic screening tests in 27 patients. Among these 27 subjects, additional phenotypic enumeration of T-cell subsets, expression of activation markers in T cells, and production of cytokines in response to T-cell stimulants were studied in 12 CdLS subjects compared with 12 normal case control subjects. Recurrent infections were reported at high frequency in CdLS patients and included chronic ear infections (53%), chronic viral respiratory infections (46%), pneumonia (42%), sinus infections (33%), oral candidiasis (13%), sepsis (6%), and bacterial skin infections (4%). Full immune evaluation in 27 subjects led to identification of 9 cases of antibody deficiency syndrome in patients with severe forms of CdLS. Subjects with CdLS had decreased percentages of T regulatory cells and T follicular helper cells compared with normal control subjects (P < .05). This study identified for the first time a high frequency of antibody deficiency in CdLS subjects, indicating a critical need for screening and management of immunodeficiency in CdLS patients with a history of well-documented severe or recurrent infections. Furthermore, our results indicate that impaired T-cell populations may be associated with antibody deficiency in CdLS.

  10. Cornelia de Lange syndrome, cohesin, and beyond

    PubMed Central

    Liu, J; Krantz, ID

    2010-01-01

    Cornelia de Lange syndrome (CdLS) (OMIM #122470, #300590 and #610759) is a dominant genetic disorder with multiple organ system abnormalities which is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Mutations in three cohesin proteins, a key regulator of cohesin, NIPBL, and two structural components of the cohesin ring SMC1A and SMC3, etiologically account for about 65% of individuals with CdLS. Cohesin controls faithful chromosome segregation during the mitotic and meiotic cell cycles. Multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double-strand DNA break repair and long-range regulation of transcription. Moreover, chromosome instability was recently associated with defective sister chromatid cohesion in several cancer studies, and an increasing number of human developmental disorders is being reported to result from disruption of this pathway. Here, we will discuss the human disorders caused by alterations of cohesin function (termed ‘cohesinopathies’), with an emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS-related proteins. PMID:19793304

  11. Sleep disorders in Cornelia de Lange syndrome.

    PubMed

    Zambrelli, Elena; Fossati, Chiara; Turner, Katherine; Taiana, Matteo; Vignoli, Aglaia; Gervasini, Cristina; Russo, Silvia; Furia, Francesca; Masciadri, Maura; Ajmone, Paola; Kullman, Gaia; Canevini, Maria Paola; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. Sleep disturbances have been frequently reported in CdLS, but these have not been completely characterized, and prevalence data are conflicting. The aim of this paper is to characterize and determine the prevalence of sleep disorders in CdLS patients by means of a validated questionnaire. From November 2012 to November 2013, we asked 46 consecutive parents/caregivers of CdLS patients aged more than 3 years old to fill out the sleep disturbances scale for children (SDSC). The subjects were also characterized by the presence of epilepsy, intellectual disability (ID), behavioral problems, CdLS severity score, gastroesophageal reflux disease (GERD), and genetic test results. An abnormal total sleep score was found in 7 patients (15.2%), 26 (56.5%) showed a borderline total score, and 18 (39.1%) had an abnormal score for at least one SDSC factor. In our study sleep disorders were found to be positively associated to presence of epilepsy, GERD, ID, and behavioral disturbances. No correlation was evident with specific mutations of the different genes, BMI, and severity score. Our results confirm that sleep disorders represent a common problem in CdLS, with higher incidence than in the normal population. In these patients sleep disorders seem to be more prevalent in comorbid settings, representing a clinical indicator for different medical and neuropsychiatric disorders. Better knowledge and characterization of typology of sleep disorders in CdLS patients could permit a more specific therapeutic approach. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Language Acquisition in a Child with Cornelia De Lange Syndrome.

    ERIC Educational Resources Information Center

    Goodban, Marjorie T.

    The paper describes a successful attempt to stimulate expressive language in Becky, a young child with Cornelia de Lange syndrome, a condition characterized by moderate to severe mental retardation, dwarfed stature, and excessive body hair. The child participated in infant stimulation and individual speech therapy and her expressive output has…

  13. Characteristics of Autism Spectrum Disorder in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Moss, Jo; Howlin, Patricia; Magiati, Iliana; Oliver, Chris

    2012-01-01

    Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in…

  14. Language Acquisition in a Child with Cornelia De Lange Syndrome.

    ERIC Educational Resources Information Center

    Goodban, Marjorie T.

    The paper describes a successful attempt to stimulate expressive language in Becky, a young child with Cornelia de Lange syndrome, a condition characterized by moderate to severe mental retardation, dwarfed stature, and excessive body hair. The child participated in infant stimulation and individual speech therapy and her expressive output has…

  15. Self-Injury in the De Lange Syndrome.

    ERIC Educational Resources Information Center

    Singh, N. N.; Pulman, Ruth M.

    1979-01-01

    Psychological treatment techniques for the control of self-injury in a 13-year-old male with de Lange syndrome (a rare disorder characterized by retarded mental and physical development) are presented. Techniques, which included mild punishment, time out, and differential reinforcement, produced a clinically significant control of self-injurious…

  16. Characteristics of Autism Spectrum Disorder in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Moss, Jo; Howlin, Patricia; Magiati, Iliana; Oliver, Chris

    2012-01-01

    Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in…

  17. Chromosome 13q deletion with Cornelia de Lange syndrome phenotype.

    PubMed

    Ngo, C T; Alhady, M; Tan, A K; Norlasiah, I Siti; Ong, G B; Chua, C N

    2007-03-01

    A 3-year-old girl with facial dysmorphic features suggestive of Cornelia de Lange syndrome was seen in the ophthalmology unit for a right leukocoria. The leukocoria was found to be caused by a large retinoblastoma and the right eye was enucleated. Chromosomal analysis revealed partial chromosome 13q deletion involving band 14 which is associated with a high risk of retinoblastoma. This case shows that patient with chromosome 13q deletion syndrome cannot be diagnosed based on dysmorphic features only. Chromosomal analysis is warranted in all infants with facial dysmorphism suggestive of Cornelia de Lange syndrome so that those with chromosome 13q deletion can be referred early for early detection of retinoblastoma.

  18. Cornelia de Lange Syndrome: A Newborn with Imperforate Anus and a NIPBL Mutation

    PubMed Central

    Mende, Rose H.; Drake, David P.; Olomi, Raimos M.; Hamel, Ben C. J.

    2012-01-01

    Cornelia de Lange syndrome is a dominantly inherited, genetically heterogeneous and clinically variable syndrome with multiple congenital anomalies and developmental delay. Gastrointestinal anomalies are common and an important cause of morbidity and mortality. We report on a newborn with a molecularly confirmed Cornelia de Lange syndrome who had an imperforate anus. This is the third report of Cornelia de Lange syndrome and imperforate anus. PMID:23304577

  19. Cornelia de Lange syndrome: What every otolaryngologist should know.

    PubMed

    Eliason, Michael J; Melzer, Jonathan M; Gallagher, Thomas Q

    2017-08-01

    Cornelia de Lange Syndrome (CdLS) can be expressed in multiple organ systems requiring a variety of specialists, including pediatric otolaryngology. We present the case of a 20-month-old boy with CdLS actively managed by an aerodigestive team consisting of pediatric otolaryngology, pediatric pulmonology, pediatric gastroenterology, with support staff from audiology, speech, and nutrition. His presentation included mixed hearing loss, dysphagia, microaspiration, gastroesophageal reflux, and failure to thrive. We submit this challenging case of CdLS with a review of the literature to focus specific attention on the otolaryngic manifestations of the syndrome and to discuss the benefits of a multidisciplinary approach to these unique patients.

  20. Cornelia de-lange syndrome: a case report.

    PubMed

    Mehta, Diana Noshir; Bhatia, Rupinder

    2013-05-01

    Cornelia de-Lange syndrome is a congenital anomaly syndrome characterized by distinctive facial dysmorphism, primordial short stature, hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly. Craniofacial features include synophrys, arched eyebrows, long eyelashes, small widely spaced teeth and microcephaly. IQ ranges from between 30 and 102 with an average of 53. Many individuals demonstrate autistic and self-destructive tendencies. It is an autosomal dominant disorder caused by specific gene mutations and occurrence is one in 30,000 to 50,000 children. This article describes a report of a classical case of the syndrome of a 10-year-old boy and emphasizes the oral and systemic findings. The role of the pediatric dentist, with his expertize in prevention, skills of behavior management and timely referral to medical speciality, is of paramount importance in the management of children with this syndrome. How to cite this article: Mehta DN, Bhatia R. Cornelia De-Lange Syndrome: A Case Report. Int J Clin Pediatr Dent 2013;6(2):115-118.

  1. Cornelia De-Lange Syndrome: A Case Report

    PubMed Central

    Bhatia, Rupinder

    2013-01-01

    ABSTRACT Cornelia de-Lange syndrome is a congenital anomaly syndrome characterized by distinctive facial dysmorphism, primordial short stature, hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly. Craniofacial features include synophrys, arched eyebrows, long eyelashes, small widely spaced teeth and microcephaly. IQ ranges from between 30 and 102 with an average of 53. Many individuals demonstrate autistic and self-destructive tendencies. It is an autosomal dominant disorder caused by specific gene mutations and occurrence is one in 30,000 to 50,000 children. This article describes a report of a classical case of the syndrome of a 10-year-old boy and emphasizes the oral and systemic findings. The role of the pediatric dentist, with his expertize in prevention, skills of behavior management and timely referral to medical speciality, is of paramount importance in the management of children with this syndrome. How to cite this article: Mehta DN, Bhatia R. Cornelia De-Lange Syndrome: A Case Report. Int J Clin Pediatr Dent 2013;6(2):115-118. PMID:25206204

  2. Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Oliver, Chris; Nelson, Lisa; Richards, Caroline; Hall, Scott

    2013-01-01

    An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n = 130, M age = 17.19), Fragile X syndrome (n = 182, M age = 16.94), and autism spectrum disorder (n = 142, M…

  3. Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Oliver, Chris; Nelson, Lisa; Richards, Caroline; Hall, Scott

    2013-01-01

    An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n = 130, M age = 17.19), Fragile X syndrome (n = 182, M age = 16.94), and autism spectrum disorder (n = 142, M…

  4. Jervell and Lange-Nielsen Syndrome (Long QT Syndrome).

    ERIC Educational Resources Information Center

    Hulbert, T. P.

    1994-01-01

    Clinical features, pathogenetic hypotheses, and symptoms of the cardio-auditory or surdo-cardiac disorder first reported by Jervell and Lange-Nielsen are described, and methods of diagnosis and treatment are presented, to alert teachers and other professionals to potentially life-threatening symptoms they may observe when working with deaf and…

  5. Jervell and Lange-Nielsen Syndrome (Long QT Syndrome).

    ERIC Educational Resources Information Center

    Hulbert, T. P.

    1994-01-01

    Clinical features, pathogenetic hypotheses, and symptoms of the cardio-auditory or surdo-cardiac disorder first reported by Jervell and Lange-Nielsen are described, and methods of diagnosis and treatment are presented, to alert teachers and other professionals to potentially life-threatening symptoms they may observe when working with deaf and…

  6. The Association Between Environmental Events and Self-Injurious Behaviour in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Moss, J.; Oliver, C.; Hall, S.; Arron, K.; Sloneem, J.; Petty, J.

    2005-01-01

    There has been limited empirical research into the environmental causes of self-injury in Cornelia de Lange syndrome. The present study examined the variability of self-injurious behaviour in Cornelia de Lange syndrome across environmental setting events. Additionally, the association between setting events and more specific environmental events…

  7. Prevalence of Autism Spectrum Phenomenology in Cornelia de Lange and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna F.; Oliver, Chris; Berg, Katy; Kaur, Gurmeash; Jephcott, Lesley; Cornish, Kim

    2008-01-01

    Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat…

  8. A Boy with a Mild Case of Cornelia de Lange Syndrome with Above Average Intelligence.

    ERIC Educational Resources Information Center

    Lacassie, Yves; Bobadilla, Olga; Cambias, Ron D., Jr.

    1997-01-01

    Describes the characteristics of an 11-year-old boy who represents the only documented case of an individual with Cornelia de Lange syndrome who also has above average cognitive functioning. Major diagnostic criteria for de Lange syndrome and comparisons with other severe and mild cases are discussed. (Author/CR)

  9. Prevalence of Autism Spectrum Phenomenology in Cornelia de Lange and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna F.; Oliver, Chris; Berg, Katy; Kaur, Gurmeash; Jephcott, Lesley; Cornish, Kim

    2008-01-01

    Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat…

  10. The Association Between Environmental Events and Self-Injurious Behaviour in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Moss, J.; Oliver, C.; Hall, S.; Arron, K.; Sloneem, J.; Petty, J.

    2005-01-01

    There has been limited empirical research into the environmental causes of self-injury in Cornelia de Lange syndrome. The present study examined the variability of self-injurious behaviour in Cornelia de Lange syndrome across environmental setting events. Additionally, the association between setting events and more specific environmental events…

  11. A Boy with a Mild Case of Cornelia de Lange Syndrome with Above Average Intelligence.

    ERIC Educational Resources Information Center

    Lacassie, Yves; Bobadilla, Olga; Cambias, Ron D., Jr.

    1997-01-01

    Describes the characteristics of an 11-year-old boy who represents the only documented case of an individual with Cornelia de Lange syndrome who also has above average cognitive functioning. Major diagnostic criteria for de Lange syndrome and comparisons with other severe and mild cases are discussed. (Author/CR)

  12. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    PubMed

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP).

  13. Psychological Well-Being in Parents of Children with Angelman, Cornelia de Lange and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Griffith, G. M.; Hastings, R. P.; Oliver, C.; Howlin, P.; Moss, J.; Petty, J.; Tunnicliffe, P.

    2011-01-01

    Background: The current study focuses on mothers and fathers of children with three rare genetic syndromes that are relatively unexplored in terms of family experience: Angelman syndrome, Cornelia de Lange syndrome and Cri du Chat syndrome. Method: Parents of children with Angelman syndrome (n = 15), Cornelia de Lange syndrome (n = 16) and Cri du…

  14. Psychological Well-Being in Parents of Children with Angelman, Cornelia de Lange and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Griffith, G. M.; Hastings, R. P.; Oliver, C.; Howlin, P.; Moss, J.; Petty, J.; Tunnicliffe, P.

    2011-01-01

    Background: The current study focuses on mothers and fathers of children with three rare genetic syndromes that are relatively unexplored in terms of family experience: Angelman syndrome, Cornelia de Lange syndrome and Cri du Chat syndrome. Method: Parents of children with Angelman syndrome (n = 15), Cornelia de Lange syndrome (n = 16) and Cri du…

  15. Prevalence of autism spectrum phenomenology in Cornelia de Lange and Cri du Chat syndromes.

    PubMed

    Moss, Joanna F; Oliver, Chris; Berg, Katy; Kaur, Gurmeash; Jephcott, Lesley; Cornish, Kim

    2008-07-01

    Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat syndrome (M ages 12.4 [SD = 3.8] and 10.3 years [SD = 3.6], respectively). Twenty-one participants with Cornelia de Lange syndrome (61.8%) scored above the autism cut-off on the Autism Diagnostic Observation Schedule compared to 9 with Cri du Chat syndrome (39.2%). Prevalence of autism spectrum disorder characteristics is heightened in Cornelia de Lange syndrome. The profile of characteristics is atypical to that of idiopathic autism.

  16. Mutational Screening and Prenatal Diagnosis in Cornelia de Lange syndrome.

    PubMed

    Dave, Usha; Shetty, Dhanlaxmi

    2014-02-01

    Phenotypic variability and the lack of a diagnostic marker have complicated the rapid diagnosis and genetic counseling for Cornelia de Lange syndrome (CdLS). The clinical features of CdLS are striking and easily recognizable by characteristic facial dysmorphism, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities with severe mental retardation. The molecular diagnosis is essential for predicting prognosis and genetic counseling in the affected family, especially while planning the next pregnancy. We report here from India six cases of CdLS and how precise mutational screening in two cases helped in prenatal diagnosis and proved significant in prevention of recurrence in the affected family.

  17. On the Molecular Etiology of Cornelia de Lange Syndrome

    PubMed Central

    Dorsett, Dale; Krantz, Ian D.

    2009-01-01

    Cornelia de Lange syndrome (CdLS) is genetically heterogeneous and is usually sporadic, occurring approximately once per ten thousand births. CdLS individuals display diverse and variable deficits in growth, mental development, limbs and organs. In the past few years it has been shown that CdLS is caused by gene mutations affecting proteins involved in sister chromatid cohesion. Studies in model organisms, and more recently in human cells have revealed, somewhat unexpectedly, that the developmental deficits in CdLS likely arise from changes in gene expression. The mechanisms by which cohesion factors regulate gene expression remain to be elucidated, but current data suggest that they likely regulate transcription in multiple ways. PMID:19154515

  18. Specific neurocognitive deficits in Cornelia de Lange syndrome.

    PubMed

    Stefanatos, G A; Musikoff, H

    1994-02-01

    Cornelia de Lange Syndrome (DLS) is a dysmorphogenic disorder typically associated with severe mental retardation. This report describes a rare case with normal-range verbal intelligence and specific cognitive deficits suggestive of a developmental visuospatial disorder. This was apparent in selective deficits in the ability to integrate visual percepts, copy spatial configurations, and manipulate representations of objects in space. Visual memory and psychomotor skills were also impaired. These deficits occurred within the context of normal language abilities and language-related academic achievement. The observed pattern of neuropsychologic impairment, in addition to aspects of socioemotional development, was similar to that seen in children with developmental right-hemisphere dysfunction. These findings suggest that the factors underlying DLS can be associated with fairly specific aberrations of cortical functioning.

  19. Special cases in Cornelia de Lange syndrome: The Spanish experience.

    PubMed

    Pié, Juan; Puisac, Beatriz; Hernández-Marcos, Maria; Teresa-Rodrigo, Maria Esperanza; Gil-Rodríguez, Maria; Baquero-Montoya, Carolina; Ramos-Cáceres, Maria; Bernal, Maria; Ayerza-Casas, Ariadna; Bueno, Inés; Gómez-Puertas, Paulino; Ramos, Feliciano J

    2016-06-01

    Cornelia de Lange Syndrome (CdLS) is an autosomal dominant (NIPBL, SMC3, and RAD21) or X-linked (SMC1A and HDAC8) disorder, characterized by distinctive craniofacial appearance, growth retardation, intellectual disability, and limb anomalies. In 2005, the Spanish CdLS Reference Center was started and now we have more than 270 cases in our database. In this special issue, we describe some of the unique or atypical patients studied by our group, whose clinical features have contributed to the expansion of the CdLS classical phenotype, helping clinicians to diagnose it. We include the case of a male with unilateral tibial hypoplasia and peroneal agenesis who had a mutation in NIPBL; we also describe one patient with a mutation in NIPBL and somatic mosaicism identified by new generation sequencing techniques; we also include one patient with CdLS and Turner syndrome; and last, an interesting patient with a duplication of the SMC1A gene. Finally, we make a short review of the splicing mutations we have found in NIPBL regarding the new knowledge on the physiological variants of the gene. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Behavioral and psychiatric manifestations in Cornelia de Lange syndrome.

    PubMed

    Grados, Marco A; Alvi, Mustafa H; Srivastava, Siddharth

    2017-03-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic syndrome with clinical manifestations due to multiple affected organ systems including limbs, gastrointestinal, skin, and central nervous systems. Although the genetic basis of CdLS is now uncovered, how behavioral manifestations are associated with genetic and brain differences are less well understood. The current focused review systematically describes the main behavioral observations to date in individuals with CdLS, which have a significant impact on quality of life and adaptive functioning. The CdLS behavioral phenotype includes autistic traits as a prominent feature; however, brain imaging studies, required to understand gene-brain-behavior connections in CdLS, are scarce. Moreover, autistic features in CdLS have a greater emphasis on repetitive behaviors, including self-injurious behaviors (SIB) and expressive communication deficits, different that the core social deficit seen in idiopathic autism. Current data strongly support the use of CdLS as a model disease for repetitive behaviors and associated developmental delay manifestations. Behavioral phenotype characteristics in CdLS point to a preponderance of repetitive clinical phenomena as well as expressive verbal deficits that ought to inform specific treatment approaches in CdLS. In particular, repetitive behaviors associated with self-injury are of high negative impact on the quality of life for individuals with CdLS and their families. Treatment approaches geared to manage repetitive behaviors and self-injurious behaviors in CdLS are required in this developmental condition.

  1. Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

    PubMed

    de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

    2017-06-07

    Cornelia de Lange Syndrome (CdLS) is a heterogeneous syndrome, both clinically and genetically, in its classical form characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the Cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge there are no reports on the effect of recombinant human GH (r-hGH) treatment in CdLS patients. We present a patient born small for gestational age (SGA) with persistent severe growth retardation (height -3.4 SDS) and mild dysmorphic features, who was treated with GH from 4.3 years of age onward, and diagnosed 6 years later with CdLS using whole exome sequencing. Treatment led to a height gain of 1.6 standard deviation score (SDS) over 8 years. Treatment was interrupted shortly due to high serum IGF-1 serum values. We conclude that GH therapy appears effective and safe for short children with CdLS.

  2. [Ophthalmological manifestations of Cornelia de Lange syndrome: Case report and review of the literature].

    PubMed

    Avgitidou, G; Cursiefen, C; Heindl, L M

    2015-05-01

    A 2-year-old boy suffering from Cornelia de Lange syndrome, presented with mucopurulent ocular discharge and epiphora since birth. Irrigation and probing of the nasolacrimal system revealed and successfully treated bilateral nasolacrimal duct obstructions. Cornelia de Lange syndrome is characterized not only by typical facial features, visceral and urogenital anomalies but also by ophthalmological manifestations in 99% of cases. The most common ophthalmological disorders are synophrys, blepharitis, epiphora, hypertrichosis of the eyebrows and eyelashes, myopia, ptosis and nasolacrimal duct obstruction.

  3. Behaviour in Cornelia de Lange syndrome: a systematic review.

    PubMed

    Mulder, Paul A; Huisman, Sylvia A; Hennekam, Raoul C; Oliver, Chris; van Balkom, Ingrid D C; Piening, Sigrid

    2017-04-01

    Careful study and accurate description of behaviour are important to understand developmental challenges for individuals with Cornelia de Lange syndrome (CdLS). Here we present a systematic review of current understanding of behaviour in CdLS. A systematic search was performed for articles published between January 1946 and December 2015 evaluating autism, self-injury, and/or cognition in CdLS. After study-selection, 43 papers were included. The Cochrane quality criteria were adjusted to assign quality scores to the included studies. Participants were mostly categorized in the severe/profound developmental level. Methodology and quality were very heterogeneous, as well as reporting occurrence of autism. Self-injurious behaviour was reported in 15 papers. Physical conditions were reported in 21 studies, mostly related to hearing and vision. Only nine studies mentioned details about medication. Comparison of presented results was hindered by heterogeneous assessment methods. Improving our understanding of behavioural characteristics in CdLS requires more uniform methodology. We propose a criterion standard of instruments that can ideally be used in assessment of behaviour and development. This will improve understanding of behaviour in the context of developmental level and daily functioning. © 2016 Mac Keith Press.

  4. Precocious Sister Chromatid Separation (PSCS) in Cornelia de Lange Syndrome

    PubMed Central

    Kaur, Maninder; DeScipio, Cheryl; McCallum, Jennifer; Yaeger, Dinah; Devoto, Marcella; Jackson, Laird G.; Spinner, Nancy B.; Krantz, Ian D.

    2009-01-01

    The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited multisystem developmental disorder. The phenotype consists of characteristic facial features, hirsutism, abnormalities of the upper extremities ranging from subtle changes in the phalanges and metacarpal bones to oligodactyly and phocomelia, gastroesophageal dysfunction, growth retardation, and neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000. Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases. To date, mutations in this gene have been identified in over 45% of individuals with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although its function in mammalian systems has not yet been elucidated, sequence homologs of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion during mitosis, and a similar role was recently demonstrated for Nipped-B in Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL mutation negative) with CdLS were evaluated for evidence of precocious sister chromatid separation (PSCS). We screened 50 metaphases from each proband and found evidence of PSCS in 41% (compared to 9% in control samples). These studies indicate that NIPBL may play a role in sister chromatid cohesion in humans as has been reported for its homologs in Drosophila and yeast. PMID:16100726

  5. Clinical Report: Germline Mosaicism in Cornelia de Lange Syndrome

    PubMed Central

    Slavin, Thomas P.; Lazebnik, Noam; Clark, Dinah M.; Vengoechea, Jaime; Cohen, Leslie; Kaur, Maninder; Konczal, Laura; Crowe, Carol A.; Corteville, Jane E.; Nowaczyk, Malgorzata J.; Byrne, Janice L.; Jackson, Laird G.; Krantz, Ian D.

    2012-01-01

    Cornelia de Lange syndrome (CdLS) is a genetic disorder associated with delayed growth, intellectual disability, limb reduction defects and characteristic facial features. Germline mosaicism has been a described mechanism for CdLS when there are several affected offspring of apparently unaffected parents. Presently, the recurrence risk for CdLS has been estimated to be as high as 1.5%; however, this figure may be an underrepresentation. We report on the molecularly defined germline mosaicism cases from a large CdLS database, representing the first large case series on germline mosaicism in CdLS. Of the 12 families, eight have been previously described; however, four have not. No one specific gene mutation, either in the NIPBL or the SMC1A gene, was associated with an increased risk for germline mosaicism. Suspected or confirmed cases of germline mosaicism in our database range from a conservative 3.4% up to 5.4% of our total cohort. In conclusion, the potential reproductive recurrence risk due to germline mosiacism should be addressed in prenatal counseling for all families who have had a previously affected pregnancy or child with CdLS. PMID:22581668

  6. Cornelia de Lange syndrome: Congenital heart disease in 149 patients.

    PubMed

    Ayerza Casas, Ariadna; Puisac Uriol, Beatriz; Teresa Rodrigo, María Esperanza; Hernández Marcos, María; Ramos Fuentes, Feliciano J; Pie Juste, Juan

    2017-10-11

    Cornelia de Lange syndrome (CdLS) is produced by mutations in genes that encode regulatory or structural proteins of the cohesin complex. Congenital heart disease (CHD) is not a major criterion of the disease, but it affects many individuals. The objective of this study was to study the incidence and type of CHD in patients with CdLS. Cardiological findings were evaluated in 149 patients with CdLS and their possible relationship with clinical and genetic variables. A percentage of 34.9 had CHD (septal defects 50%, pulmonary stenosis 27%, aortic coarctation 9.6%). The presence of CHD was related with neonatal hospitalisation (P=.04), hearing loss (P=.002), mortality (P=.09) and lower hyperactivity (P=.02), it being more frequent in HDAC8+ patients (60%), followed by NIPBL+ (33%) and SMC1A+ (28.5%). While septal defects predominate in NIPBL+, pulmonary stenosis is more common in HDAC8+. Patients with CdLS have a high incidence of CHD, which varies according to the affected gene, the most frequent findings being septal defects and pulmonary stenosis. Perform a cardiologic study in all these patients is suggested. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report.

    PubMed

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-06-13

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.

  8. Natural History of Aging in Cornelia de Lange Syndrome

    PubMed Central

    KLINE, ANTONIE D.; GRADOS, MARCO; SPONSELLER, PAUL; LEVY, HOWARD P.; BLAGOWIDOW, NATALIE; SCHOEDEL, CHRISTIANNE; RAMPOLLA, JONI; CLEMENS, DOUGLAS K.; KRANTZ, IAN; KIMBALL, AMY; PICHARD, CARMEN; TUCHMAN, DAVID

    2016-01-01

    Observations about the natural history of aging in Cornelia de Lange syndrome (CdLS) are made, based on 49 patients from a multidisciplinary clinic for adolescents and adults. The mean age was 17 years. Although most patients remain small, obesity may develop. Gastroesophageal reflux persists or worsens, and there are early long-term sequelae, including Barrett esophagus in 10%; other gastrointestinal findings include risk for volvulus, rumination, and chronic constipation. Submucous cleft palate was found in 14%, most undetected before our evaluation. Chronic sinusitis was noted in 39%, often with nasal polyps. Blepharitis improves with age; cataracts and detached retina may occur. Decreased bone density is observed, with occasional fractures. One quarter have leg length discrepancy and 39% scoliosis. Most females have delayed or irregular menses but normal gynecologic exams and pap smears. Benign prostatic hypertrophy occurred in one male prior to 40 years. The phenotype is variable, but there is a distinct pattern of facial changes with aging. Premature gray hair is frequent; two patients had cutis verticis gyrata. Behavioral issues and specific psychiatric diagnoses, including self-injury, anxiety, attention-deficit disorder, autistic features, depression, and obsessive-compulsive behavior, often worsen with age. This work presents some evidence for accelerated aging in CdLS. Of 53% with mutation analysis, 55% demonstrate a detectable mutation in NIPBL or SMC1A. Although no specific genotype–phenotype correlations have been firmly established, individuals with missense mutations in NIPBL and SMC1A appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made. PMID:17640042

  9. Analysis of Intentional Communication in Severely Handicapped Children with Cornelia-de-Lange Syndrome.

    ERIC Educational Resources Information Center

    Sarimski, Klaus

    2002-01-01

    Intentional communicative acts were assessed in 13 children (ages 2-8) with Cornelia-de-Lange syndrome with a severe mental disability and compared to children with Down and 5p syndromes. The mean number of intentional communicative acts was significantly lower. Analysis of play behaviors revealed the differences were specific for the…

  10. Facial Expression of Affect in Children with Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Collis, L.; Moss, J.; Jutley, J.; Cornish, K.; Oliver, C.

    2008-01-01

    Background: Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of…

  11. Facial Expression of Affect in Children with Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Collis, L.; Moss, J.; Jutley, J.; Cornish, K.; Oliver, C.

    2008-01-01

    Background: Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of…

  12. Infant Attentional Behaviours as Prognostic Indicators in Cornelia-de-Lange Syndrome

    ERIC Educational Resources Information Center

    Sarimski, Klaus

    2007-01-01

    Background: Cornelia-de-Lange syndrome is a rare congenital syndrome with poor social relatedness as one of several characteristics of its behavioural phenotype. Methods: Video observations were collected from seven children in their first year of life and again with age 2-4 years. Data were analysed for distribution of object-related and social…

  13. Analysis of Intentional Communication in Severely Handicapped Children with Cornelia-de-Lange Syndrome.

    ERIC Educational Resources Information Center

    Sarimski, Klaus

    2002-01-01

    Intentional communicative acts were assessed in 13 children (ages 2-8) with Cornelia-de-Lange syndrome with a severe mental disability and compared to children with Down and 5p syndromes. The mean number of intentional communicative acts was significantly lower. Analysis of play behaviors revealed the differences were specific for the…

  14. Infant Attentional Behaviours as Prognostic Indicators in Cornelia-de-Lange Syndrome

    ERIC Educational Resources Information Center

    Sarimski, Klaus

    2007-01-01

    Background: Cornelia-de-Lange syndrome is a rare congenital syndrome with poor social relatedness as one of several characteristics of its behavioural phenotype. Methods: Video observations were collected from seven children in their first year of life and again with age 2-4 years. Data were analysed for distribution of object-related and social…

  15. Delineating the profile of autism spectrum disorder characteristics in Cornelia de Lange and Fragile X syndromes.

    PubMed

    Moss, Joanna; Oliver, Chris; Nelson, Lisa; Richards, Caroline; Hall, Scott

    2013-01-01

    An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n  =  130, M age  =  17.19), Fragile X syndrome (n  =  182, M age  =  16.94), and autism spectrum disorder (n  =  142, M age  =  15.19), who were comparable on chronological age. Using the Social Communication Questionnaire, the proportion meeting cutoff for autism spectrum disorder and autism was 78.6%, and 45.6%, respectively, in Cornelia de Lange syndrome and 83.6% and 48.6% in Fragile X syndrome. Domain and item analyses indicate differing, atypical autism spectrum disorder profiles in Fragile X and Cornelia de Lange syndromes. A limited association between adaptive behavior and autism spectrum disorder was identified in all groups. The findings have implications for intervention in genetic syndromes and conceptualization of autism spectrum disorder in the wider population.

  16. [Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

    PubMed

    Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

    2017-06-01

    Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

  17. Behavioral Phenotype and Autism Spectrum Disorders in Cornelia de Lange Syndrome.

    PubMed

    Parisi, Lucia; Di Filippo, Teresa; Roccella, Michele

    2015-09-30

    Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), are responsible for approximately 50-60% of CdLS cases. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in CdLS. However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. A significantly higher prevalence of self-injury are evident in CdLS. Self-injury was associated with repetitive and impulsive behavior. This study describes the behavioral phenotype of four children with Cornelia de Lange syndrome and ASDs and rehabilitative intervention that must be implemented.

  18. Unpredictable drug reaction in a child with Cornelia de Lange syndrome.

    PubMed

    Stevic, Marija; Milojevic, Irina; Bokun, Zlatko; Simic, Dusica

    2015-02-01

    Preoperative use of midazolam sedation is mandatory during induction of anesthesia in noncooperative and hyperactive children to prevent possible obstacles. Unusual drug reactions rarely occur in patients undergoing anesthesia or in intensive care unit. This report describes an unpredictable drug reaction after a routine midazolam premedication in a patient with no history of allergy. There has been no literature data yet to show that midazolam can provoke respiratory problems in patients with Cornelia de Lange Syndrome. In our opinion midazolam should be avoided in patients with Cornelia de Lange Syndrome, which we enforced after first unpredictable reaction.

  19. The Behavioural Phenotype of Cornelia de Lange Syndrome: A Study of 56 Individuals

    ERIC Educational Resources Information Center

    Basile, Emanuele; Villa, L.; Selicorni, A.; Molteni, M.

    2007-01-01

    Background: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. Methods: In total, 56 individuals with CdLS…

  20. Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.

    ERIC Educational Resources Information Center

    Wahl, Richard A.; Macdonald, Dick, II

    1980-01-01

    The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…

  1. Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.

    ERIC Educational Resources Information Center

    Wahl, Richard A.; Macdonald, Dick, II

    1980-01-01

    The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…

  2. Self-Injurious Behavior, Self-Restraint, and Compulsive Behaviors in Cornelia de Lange Syndrome.

    ERIC Educational Resources Information Center

    Hyman, Philippa; Oliver, Chris; Hall, Scott

    2002-01-01

    Analysis of questionnaires completed by caregivers of 77 individuals with Cornelia de Lange syndrome in the United Kingdom found a significant association between self-injurious behaviors and self-restraint, and those displaying both behaviors displayed significantly more compulsions than did those not exhibiting them. Findings extend the…

  3. Health and Sleep Problems in Cornelia de Lange Syndrome: A Case Control Study

    ERIC Educational Resources Information Center

    Hall, S. S.; Arron, K.; Sloneem, J.; Oliver, C.

    2008-01-01

    Background: Self-injury, sleep problems and health problems are commonly reported in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with appropriately matched participants. The relationship between these areas and comparison to a control group is warranted. Method: 54 individuals with CdLS were compared with 46 participants with…

  4. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 1. Prevalence and Phenomenology

    ERIC Educational Resources Information Center

    Oliver, C.; Sloneem, J.; Hall, S.; Arron, K.

    2009-01-01

    Background: Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS. Methods: A total of 54 participants with CdLS were compared with 46 individuals who were comparable…

  5. Health and Sleep Problems in Cornelia de Lange Syndrome: A Case Control Study

    ERIC Educational Resources Information Center

    Hall, S. S.; Arron, K.; Sloneem, J.; Oliver, C.

    2008-01-01

    Background: Self-injury, sleep problems and health problems are commonly reported in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with appropriately matched participants. The relationship between these areas and comparison to a control group is warranted. Method: 54 individuals with CdLS were compared with 46 participants with…

  6. The Behavioural Phenotype of Cornelia de Lange Syndrome: A Study of 56 Individuals

    ERIC Educational Resources Information Center

    Basile, Emanuele; Villa, L.; Selicorni, A.; Molteni, M.

    2007-01-01

    Background: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. Methods: In total, 56 individuals with CdLS…

  7. Normal Language Skills and Normal Intelligence in a Child with de Lange Syndrome.

    ERIC Educational Resources Information Center

    Cameron, Thomas H.; Kelly, Desmond P.

    1988-01-01

    The subject of this case report is a two-year, seven-month-old girl with de Lange syndrome, normal intelligence, and age-appropriate language skills. She demonstrated initial delays in gross motor skills and in receptive and expressive language but responded well to intensive speech and language intervention, as well as to physical therapy.…

  8. Self-Injurious Behavior, Self-Restraint, and Compulsive Behaviors in Cornelia de Lange Syndrome.

    ERIC Educational Resources Information Center

    Hyman, Philippa; Oliver, Chris; Hall, Scott

    2002-01-01

    Analysis of questionnaires completed by caregivers of 77 individuals with Cornelia de Lange syndrome in the United Kingdom found a significant association between self-injurious behaviors and self-restraint, and those displaying both behaviors displayed significantly more compulsions than did those not exhibiting them. Findings extend the…

  9. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 1. Prevalence and Phenomenology

    ERIC Educational Resources Information Center

    Oliver, C.; Sloneem, J.; Hall, S.; Arron, K.

    2009-01-01

    Background: Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS. Methods: A total of 54 participants with CdLS were compared with 46 individuals who were comparable…

  10. Prenatal/neonatal pathology in two cases of Cornelia de Lange syndrome harboring novel mutations of NIPBL.

    PubMed

    Lalatta, Faustina; Russo, Silvia; Gentilin, Barbara; Spaccini, Luigina; Boschetto, Chiara; Cavalleri, Florinda; Masciadri, Maura; Gervasini, Cristina; Bentivegna, Angela; Castronovo, Paola; Larizza, Lidia

    2007-03-01

    This study reviews prenatal findings in two cases with a suspected diagnosis of Cornelia de Lange Syndrome, a multisystem disorder characterized by somatic defects and mental retardation, that were later confirmed by postmortem examination and molecular testing. Although the correlation between the Cornelia de Lange Syndrome genotype and phenotype is still unclear, preliminary data indicate several severe phenotypic features that are likely to be detected prenatally in NIPBL-mutated patients. We report on two prenatal/neonatal cases with unusual pathologic findings indicating Cornelia de Lange Syndrome. The first, with suspected Cornelia de Lange Syndrome after a set of typical dysmorphisms was noted by prenatal ultrasound, was confirmed by a physical examination after termination of the pregnancy. The second was diagnosed neonatally on the basis of typical clinical signs. Medical complications led to death within the first month of life. Molecular analysis of NIPBL, the gene that codes for delangin (a component of the cohesin complex), performed postnatally detected two de novo mutations: a missense change (P2056L) in a highly conserved residue and a nonsense alteration (S2490 replaced by a stop codon). We suggest that early diagnosis of Cornelia de Lange Syndrome would be made much easier by the assemblage of a set of prenatal diagnostic features and criteria in Cornelia de Lange Syndrome cases that have been confirmed by direct physical and molecular examinations. We also suggest that Cornelia de Lange Syndrome genotype-phenotype correlations need to be extended to prenatal cases.

  11. Aesthetic and functional management of a patient with Cornelia de Lange syndrome

    PubMed Central

    Johns, Dexton Antony; Bhonsale, Dnyanesh L.; Shivashanker, V. Y.; Johns, Manu

    2012-01-01

    Cornelia de Lange syndrome is a syndrome of multiple congenital anomalies. The genetic and molecular bases of these lesions are not clear. It is divided into three types based on the severity of the anomaly. Dental findings revealed contracted maxilla, malaligned teeth, multiple impacted and missing teeth. This article describes the successful management of upper central incisor with lateral opening in the apical third on the mesial surface of the root along with aesthetic and functional rehabilitation. PMID:22629076

  12. A case of third trimester diagnosis of Cornelia de Lange syndrome.

    PubMed

    Kanellopoulos, V; Iavazzo, C; Tzanatou, C; Papadakis, E; Tassis, K

    2011-01-01

    The objective is to present a rare case of late diagnosis of Cornelia de Lange syndrome. A 27-year-old pregnant woman (gravida 1, para 0) was referred to our Fetal Medicine Department during her 33rd week of gestation due to intrauterine growth restriction (IUGR) and polyhydramnios. The ultrasound scanning confirmed the findings and furthermore, the 3-D examination revealed minor facial dysmorphisms, limb abnormalities, and hypertrichosis. The fetus died 1 week post-diagnosis due to unknown reason and the woman underwent an induction of labor. Postmortem examination confirmed the diagnosis of Cornelia de Lange syndrome. The prognosis of the syndrome is severe. Termination of pregnancy before viability is proposed. Genetic counseling is necessary.

  13. De Lange syndrome: subjective and objective comparison of the classical and mild phenotypes.

    PubMed Central

    Allanson, J E; Hennekam, R C; Ireland, M

    1997-01-01

    Classical de Lange syndrome presents with a striking face, pronounced growth and mental retardation, and variable limb deficiencies. Over the past five years, a mild variant has been defined, with less significant psychomotor retardation, less marked pre- and postnatal growth deficiency, and an uncommon association with major malformations, although mild limb anomalies may be present. We have evaluated 43 subjects with de Lange syndrome, 30 with classical features, aged from birth to 21 years, and 13 with the mild phenotype, aged from 18 months to 30 years. In addition to assessment of gestalt and facial change with time, detailed craniofacial measurements have been obtained on each subject and composite pattern profiles compiled. The characteristic face of classical de Lange syndrome is present at birth and changes little throughout life, although there is some lengthening of the face with age and the jaw becomes squared. In mild de Lange syndrome, the characteristic classical appearance may be present at birth, but in some subjects it may be two or three years before the typical face is obvious. In general, the overall impression is less striking, perhaps because of increased facial expression and greater alertness. With age, the face loses the characteristic appearance, the nasal height increases, the philtrum does not seem as long, and the upper vermilion is full and everted, although the crescent shaped mouth with downturned corners remains. Eyebrows may be full and bushy. Objective comparison of the face in mild and classical de Lange syndrome, through the use of craniofacial pattern profiles, shows marked similarity of patterns at 4 to 9 years; both groups have microbrachycephaly, but the individual dimensions of the mild group are slightly closer to normal than their classical counterparts. The correlation coefficient is high (0.83). In the adult groups, similarity of patterns remains but is less marked. The normalisation of scores in the mild group is more

  14. Dental Management of Cornelia de Lange Syndrome: A Rare Case Report

    PubMed Central

    Nagpal, Mehak; Gulia, Shweta; Sachdev, Vinod

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital defect often called as Amsterdam dwarfism. The physical phenotype of CdLS includes low birth body weight, short stature and facio-cranial dysmorphia. The diagnosis of the syndrome is based on clinical grounds as there is no biochemical or chromosomal markers for CDLS that makes its diagnosis more complicated. The purpose of this paper is to present a clinical report of a boy emphasizing the importance of multidisciplinary approach for the diagnosis and treatment of this syndrome. PMID:25859533

  15. Cervical spine malformation in cornelia de lange syndrome: a report of three patients.

    PubMed

    Bettini, Laura Rachele; Locatelli, Laura; Mariani, Milena; Cianci, Paola; Giussani, Carlo; Canonico, Francesco; Cereda, Anna; Russo, Silvia; Gervasini, Cristina; Biondi, Andrea; Selicorni, Angelo

    2014-06-01

    Cornelia de Lange syndrome (CdLS) is a complex genetic disease with skeletal involvement mostly related to upper limb malformations. We report on three males with clinical and molecular diagnoses of CdLS. Besides typical CdLS features, all showed different cervical spine malformations. To the best of our knowledge, this is an unusual malformation in the CdLS phenotypic spectrum. © 2014 Wiley Periodicals, Inc.

  16. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 2. Association with Environmental Events

    ERIC Educational Resources Information Center

    Sloneem, J.; Arron, K.; Hall, S. S.; Oliver, C.

    2009-01-01

    Background: Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods: We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched…

  17. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 2. Association with Environmental Events

    ERIC Educational Resources Information Center

    Sloneem, J.; Arron, K.; Hall, S. S.; Oliver, C.

    2009-01-01

    Background: Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods: We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched…

  18. Behavioral Phenotype and Autism Spectrum Disorders in Cornelia de Lange Syndrome

    PubMed Central

    Parisi, Lucia; Di Filippo, Teresa; Roccella, Michele

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), are responsible for approximately 50-60% of CdLS cases. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in CdLS. However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. A significantly higher prevalence of self-injury are evident in CdLS. Self-injury was associated with repetitive and impulsive behavior. This study describes the behavioral phenotype of four children with Cornelia de Lange syndrome and ASDs and rehabilitative intervention that must be implemented. PMID:26605036

  19. A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome.

    PubMed

    Nizon, M; Henry, M; Michot, C; Baumann, C; Bazin, A; Bessières, B; Blesson, S; Cordier-Alex, M-P; David, A; Delahaye-Duriez, A; Delezoïde, A-L; Dieux-Coeslier, A; Doco-Fenzy, M; Faivre, L; Goldenberg, A; Layet, V; Loget, P; Marlin, S; Martinovic, J; Odent, S; Pasquier, L; Plessis, G; Prieur, F; Putoux, A; Rio, M; Testard, H; Bonnefont, J-P; Cormier-Daire, V

    2016-05-01

    Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to a heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: (i) intrauterine growth retardation and postnatal short stature, (ii) feeding difficulties and/or gastro-oesophageal reflux, (iii) microcephaly, (iv) intellectual disability, and (v) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and 3 in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for 20 cases which do not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counselling. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. A Longitudinal Follow-Up Study of Affect in Children and Adults with Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Nelson, Lisa; Moss, Jo; Oliver, Chris

    2014-01-01

    Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N = 67), cri du chat syndrome (CdCS; N = 42), and Fragile X syndrome (FXS; N = 142) completed the Mood, Interest and Pleasure…

  1. A Longitudinal Follow-Up Study of Affect in Children and Adults with Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Nelson, Lisa; Moss, Jo; Oliver, Chris

    2014-01-01

    Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N = 67), cri du chat syndrome (CdCS; N = 42), and Fragile X syndrome (FXS; N = 142) completed the Mood, Interest and Pleasure…

  2. Epileptic features in Cornelia de Lange syndrome: case report and literature review.

    PubMed

    Pavlidis, Elena; Cantalupo, Gaetano; Bianchi, Sara; Piccolo, Benedetta; Pisani, Francesco

    2014-11-01

    Cornelia de Lange syndrome is a rare genetic disease, caused by mutations in three known different genes: NIBPL (crom 5p), SMC1A (crom X) and SMC3 (crom 10q), that account for about 65% of cases. This syndrome is characterized by distinctive facial features, psychomotor delay, growth retardation since the prenatal period (second trimester of pregnancy), hands and feet abnormalities, and involvement of other organs/systems. SMC1A and SMC3 mutations are responsible for a mild phenotype of the syndrome. We report the electroclinical features of epilepsy in a child with a mild Cornelia de Lange syndrome and furthermore we reviewed the descriptions of the epileptic findings available in the literature in patients with such syndrome. A large heterogeneity of the epileptic findings in the literature is reported. The presence of epilepsy could be related to pathophysiological factors independent of those implicated in the characterization of main classical phenotypic features. A more detailed description of the epileptic findings could help clinicians in the diagnosis of this syndrome in those cases lacking of the typical features. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Face scanning and spontaneous emotion preference in Cornelia de Lange syndrome and Rubinstein-Taybi syndrome.

    PubMed

    Crawford, Hayley; Moss, Joanna; McCleery, Joseph P; Anderson, Giles M; Oliver, Chris

    2015-01-01

    Existing literature suggests differences in face scanning in individuals with different socio-behavioural characteristics. Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RTS) are two genetically defined neurodevelopmental disorders with unique profiles of social behaviour. Here, we examine eye gaze to the eye and mouth regions of neutrally expressive faces, as well as the spontaneous visual preference for happy and disgusted facial expressions compared to neutral faces, in individuals with CdLS versus RTS. Results indicate that the amount of time spent looking at the eye and mouth regions of faces was similar in 15 individuals with CdLS and 17 individuals with RTS. Both participant groups also showed a similar pattern of spontaneous visual preference for emotions. These results provide insight into two rare, genetically defined neurodevelopmental disorders that have been reported to exhibit contrasting socio-behavioural characteristics and suggest that differences in social behaviour may not be sufficient to predict attention to the eye region of faces. These results also suggest that differences in the social behaviours of these two groups may be cognitively mediated rather than subcortically mediated.

  4. Cornelia De Lange syndrome: a case report of a Brazilian boy.

    PubMed

    Scarpelli, Ana C; Pordeus, Isabela A; Resende, Vera L; Castilho, Lia S; Marques, Leandro S; Paiva, Saul M

    2011-07-01

    Cornelia de Lange syndrome is a rare multisystem disorder characterized by a distinctive facial appearance, delayed growth and psychomotor skills, behavioral problems, malformation of the upper limbs, and impairment on the quality of life of affected subjects. This article reports a case of a child with the syndrome, emphasizing the orofacial manifestations. Knowledge on the etiopathological aspects and characteristic features of this condition is essential so that professionals can provide health care and help improve the quality of life of affected individuals and their families.

  5. Cornelia de Lange and Ehlers-Danlos: comorbidity of two rare syndromes.

    PubMed

    Cravero, Cora; Guinchat, Vincent; Barete, Stéphane; Consoli, Angèle

    2016-02-01

    We present a case of a young adult with both Cornelia de Lange syndrome and Ehlers-Danlos syndrome. The patient showed non-verbal autism, intellectual disability and severe/intractable self-harming behaviours that led to a life-threatening complication (ie, septicaemia). A significant reduction in the self-harming behaviours was attained in a multidisciplinary neurobehavioural inpatient unit after addressing all causes of somatic pains, managing pain using level II and III analgesics, stabilising the patient's mood, limiting the iatrogenic effects of multiple prescriptions and offering a specific psychoeducational approach.

  6. A Case Report of Cornelia De Lange Syndrome in Northern Iran; A Clinical and Diagnostic Study.

    PubMed

    Hosseininejad, Seyyed-Mohsen; Bazrafshan, Behnaz; Alaee, Ehsan

    2016-02-01

    As a rare multisystem congenital anomaly disorder, Cornelia de Lange syndrome (CdLS) is featured by delayed growth and development, distinct facial dimorphism, limb malformations and multiple organ defects. CdLS is a genetic syndrome affecting 1/10000-1/60000 neonates with unknown genetic basis. Delayed growth and development, hirsute, structural anomalies of the limbs and distinct facial dimorphism are considered as its main clinical characteristics. Introducing CdLS cases of different ethnic backgrounds could add distinctions to the phenotypic picture of the syndrome and be useful in diagnosis. Early diagnosis and decreased death rates are achievable through enhanced awareness on this syndrome. We present here a 45-day-old girl, as the first case of Cornelia in Golestan (Northern Iran), referred to our hospital with the symptoms as mentioned above.

  7. Cornelia de Lange syndrome with NIPBL mutation and mosaic Turner syndrome in the same individual

    PubMed Central

    2012-01-01

    Background Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS) results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis. Case presentation Here we report a four-year-old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA), who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells). However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X. Conclusions The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence. PMID:22676896

  8. Simultaneous Analysis of the Behavioural Phenotype, Physical Factors, and Parenting Stress in People with Cornelia De Lange Syndrome

    ERIC Educational Resources Information Center

    Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

    2009-01-01

    Background: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical…

  9. Social Behavior and Characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange, and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Howlin, Patricia; Hastings, Richard Patrick; Beaumont, Sarah; Griffith, Gemma M.; Petty, Jane; Tunnicliffe, Penny; Yates, Rachel; Villa, Darrelle; Oliver, Chris

    2013-01-01

    We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; "n" ?=? 19; mean age ?=?10.35 years), Cornelia de Lange (CdLS; "n" ?=? 15; mean age ?=?12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; "n" ?=? 19; mean age ?=? 8.80 years) syndromes. The proportion of…

  10. Effects of Social Context on Social Interaction and Self-Injurious Behavior in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Arron, Kate; Oliver, Chris; Hall, Scott; Sloneem, Jenny; Forman, Debbie; McClintock, Karen

    2006-01-01

    Cornelia de Lange syndrome is reported to be associated with self-injurious behavior (SIB) and social avoidance. We used analog methodology to examine the effect of manipulating adult social contact on social communicative behaviors and SIB in 16 children with this syndrome. For 9 participants engagement behavior was related to levels of adult…

  11. Social Behavior and Characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange, and Cri du Chat Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Howlin, Patricia; Hastings, Richard Patrick; Beaumont, Sarah; Griffith, Gemma M.; Petty, Jane; Tunnicliffe, Penny; Yates, Rachel; Villa, Darrelle; Oliver, Chris

    2013-01-01

    We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; "n" ?=? 19; mean age ?=?10.35 years), Cornelia de Lange (CdLS; "n" ?=? 15; mean age ?=?12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; "n" ?=? 19; mean age ?=? 8.80 years) syndromes. The proportion of…

  12. Effects of Social Context on Social Interaction and Self-Injurious Behavior in Cornelia de Lange Syndrome

    ERIC Educational Resources Information Center

    Arron, Kate; Oliver, Chris; Hall, Scott; Sloneem, Jenny; Forman, Debbie; McClintock, Karen

    2006-01-01

    Cornelia de Lange syndrome is reported to be associated with self-injurious behavior (SIB) and social avoidance. We used analog methodology to examine the effect of manipulating adult social contact on social communicative behaviors and SIB in 16 children with this syndrome. For 9 participants engagement behavior was related to levels of adult…

  13. Simultaneous Analysis of the Behavioural Phenotype, Physical Factors, and Parenting Stress in People with Cornelia De Lange Syndrome

    ERIC Educational Resources Information Center

    Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

    2009-01-01

    Background: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical…

  14. Psychological well-being in parents of children with Angelman, Cornelia de Lange and Cri du Chat syndromes.

    PubMed

    Griffith, G M; Hastings, R P; Oliver, C; Howlin, P; Moss, J; Petty, J; Tunnicliffe, P

    2011-04-01

    The current study focuses on mothers and fathers of children with three rare genetic syndromes that are relatively unexplored in terms of family experience: Angelman syndrome, Cornelia de Lange syndrome and Cri du Chat syndrome. Parents of children with Angelman syndrome (n =15), Cornelia de Lange syndrome (n = 16) and Cri du Chat syndrome (n = 18), and a matched comparison group of parents of children with autism and intellectual disabilities (n = 20) completed questionnaires on both psychological distress (stress, anxiety, depression) and positive psychological functioning. Parents of children with Angelman syndrome consistently reported the highest levels of psychological distress, and parents of children with Cornelia de Lange syndrome the lowest, with parents of children with Cri du Chat syndrome and autism scoring between these two. Positive psychological functioning was similar across the four aetiology groups. Parents of children with rare genetic syndromes are at risk for high levels of stress and mental health problems. Methodological issues and the practical applications of these results are discussed. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

  15. The Drosophila melanogaster Model for Cornelia de Lange Syndrome: Implications for Etiology and Therapeutics

    PubMed Central

    Dorsett, Dale

    2016-01-01

    Discovery of genetic alterations that cause human birth defects provide key opportunities to improve the diagnosis, treatment, and family counseling. Frequently, however, these opportunities are limited by the lack of knowledge about the normal functions of the affected genes. In many cases, there is more information about the gene’s orthologs in model organisms, including Drosophila melanogaster. Despite almost a billion years of evolutionary divergence, over three-quarters of genes linked to human diseases have Drosophila homologs. With a short generation time, a twenty-fold smaller genome, and unique genetic tools, the conserved functions of genes are often more easily elucidated in Drosophila than in other organisms. Here we present how this applies to Cornelia de Lange syndrome, as a model for how Drosophila can be used to increase understanding of genetic syndromes caused by mutations with broad effects on gene transcription and exploited to develop novel therapies. PMID:27097273

  16. The Drosophila melanogaster model for Cornelia de Lange syndrome: Implications for etiology and therapeutics.

    PubMed

    Dorsett, Dale

    2016-06-01

    Discovery of genetic alterations that cause human birth defects provide key opportunities to improve the diagnosis, treatment, and family counseling. Frequently, however, these opportunities are limited by the lack of knowledge about the normal functions of the affected genes. In many cases, there is more information about the gene's orthologs in model organisms, including Drosophila melanogaster. Despite almost a billion years of evolutionary divergence, over three-quarters of genes linked to human diseases have Drosophila homologs. With a short generation time, a twenty-fold smaller genome, and unique genetic tools, the conserved functions of genes are often more easily elucidated in Drosophila than in other organisms. Here we present how this applies to Cornelia de Lange syndrome, as a model for how Drosophila can be used to increase understanding of genetic syndromes caused by mutations with broad effects on gene transcription and exploited to develop novel therapies. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Pharmacological treatment of aggressive behavior and emesis in the Cornelia de Lange Syndrome.

    PubMed

    Andrasik, F; Ollendick, T H; Turner, S M; Hughes, J R

    1979-12-01

    Chlorpromazine and fluphenazine decanoate were employed to treat aggressive behavior and emesis in a 22-year-old patient with Cornelia de Lange syndrome. Institution of the above neuroleptics, following an unsuccessful trial of diazepam, produced reductions of 95.1 per cent and 37.9 per cent for aggressive behavior and emesis, respectively. Four follow-up observations, occurring at 3-week intervals, revealed maintenance of low rates of aggressive behavior and continued reductions in emesis (mean reduction of 81.5 per cent). These findings are important for their a) inclusion of direct behavioral observation as the data base, and b) initial promising effects of neuroleptics for a rare mental retardation syndrome.

  18. Cornelia de Lange syndrome - characteristics and laparoscopic treatment modalities of reflux based on own material.

    PubMed

    Szyca, Robert; Leksowski, Krzysztof

    2011-09-01

    Cornelia de Lange syndrome (typus degenerativus amstelodamensis, CdLS, Brachmann syndrome) is a complex, congenital, multi-gene anomaly characterized by mental retardation. Its features include growth inhibition, hirsutism, structural anomalies of the limbs and abnormal development of osseous structures of the face. Independent of the phenotype of the disease, 85% of patients are assumed to have symptoms of gastroesophageal reflux disease (GERD). Aspiration pneumonia is one of the complications of GERD and a main cause of death in these patients. Patients not responding to medical treatment qualify for surgery. Until recently, anti-reflux procedures for GERD in CdLS patients were performed solely via laparotomy. The contemporary gold standard is a procedure performed laparoscopically. There are a few case reports of patients with CdLS operated on for GERD with laparoscopy available in the literature. The goal of this paper is to present two cases of Cornelia de Lange syndrome treated with laparoscopic antireflux procedures. We have performed two such procedures in 14 and 16 year-old girls with typical symptoms of the syndrome, i.e. developmental and mental retardation, hirsutism, structural limb anomalies and abnormal face development. The main indications for surgery in both cases were ineffective medical treatment and persistent aspiration pneumonia and its complications as a result of the gastroesophageal reflux. Oesophageal hiatus hernia and reflux were confirmed with accessory tests in both cases. During 36 months of follow-up, according to Barents, no episode of oesophageal reflux with acidic gastric content was noted. The treated children slept well during the night and did not need hospitalization for aspiration pneumonia. Neither of them required proton pump inhibitors. It should be concluded that laparoscopic Nissen fundoplication is a safe and effective method of GERD treatment in children with CdLS.

  19. Cornelia de Lange syndrome due to mosaic NIPBL mutation: antenatal presentation with sacrococcygeal teratoma.

    PubMed

    Banait, Nishant; Fenton, Alan; Splitt, Miranda

    2015-08-14

    A male infant at 36 weeks gestation was born by section. At 20 weeks of gestation, congenital diaphragmatic hernia and sacrococcygeal teratoma had been seen on ultrasound. At birth, the infant had features suggestive of Cornelia de Lange syndrome (CdLS). He remained hypoxic despite aggressive ventilatory manoeuvres and was palliated. At postmortem, the lungs were hypoplastic. In CdLS, mutations in NIPBL are found in around 50% of cases. Mutation analysis, including multiplex ligation dependent probe amplification of the NIPBL gene from the DNA extracted from peripheral blood lymphocytes was negative, but microarray comparative genomic hybridisation on DNA from skin fibroblast showed a 0.13Mb deletion on chromosome 5p13. The deleted region includes exons 42-47 of the NIPBL gene. It is important to perform NIBPL mutation analysis on DNA from more than one tissue when testing for CdLS. 2015 BMJ Publishing Group Ltd.

  20. Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

    PubMed

    Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

    2017-03-01

    The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

  1. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance.

    PubMed

    Reid, Donna; Moss, Jo; Nelson, Lisa; Groves, Laura; Oliver, Chris

    2017-08-15

    The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

  2. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance.

    PubMed

    Reid, Donna; Moss, Jo; Nelson, Lisa; Groves, Laura; Oliver, Chris

    2017-01-01

    The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

  3. Improvement in hearing loss over time in Cornelia de Lange syndrome.

    PubMed

    Janek, Kevin C; Smith, David F; Kline, Antonie D; Benke, James R; Chen, Mei-Ling; Kimball, Amy; Ishman, Stacey L

    2016-08-01

    Patients with Cornelia de Lange Syndrome (CdLS) are reported to have conductive (CHL) and sensorineural hearing loss (SNHL), but there is little information pertaining to the progression of hearing loss over time. The goal of this study was to examine the prevalence of CHL and SNHL in adults and children with CdLS and look for changes in SNHL over time. Retrospective chart review of patients with CdLS presenting to a CdLS clinic was conducted. Also, a written survey of clinical concerns was collected from additional patients/families seen in the clinic and through the Cornelia de Lange Foundation. Seventy-eight patients (50% female) were included in the chart review. Mean age was 16.8 ± 11.4 years (range-0.6-50 years) and mean age at diagnosis of hearing loss was 4.6 ± 10.6 years (n = 26). Five patients (6.4%) had severe to profound SNHL that improved with time, including 2 who had complete normalization of audiogram results. Thirty-five families/patients completed the clinical survey, and 45.5% of the families reported a noticeable improvement of hearing over time. Conductive hearing loss and SNHL are common in CdLS. More than 50% of the patients seen in an adult CdLS clinic reported improvement in hearing loss over time, and a subset of patients had an improvement in SNHL. In light of these findings, we recommend longitudinal evaluations of hearing loss in these patients with both auditory brainstem response and otoacoustic emissions testing if SNHL is identified. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome.

    PubMed

    Cereda, Anna; Mariani, Milena; Rebora, Paola; Sajeva, Anna; Ajmone, Paola Francesca; Gervasini, Cristina; Russo, Silvia; Kullmann, Gaia; Valsecchi, Grazia; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?

    PubMed

    Avagliano, Laura; Bulfamante, Gaetano Pietro; Massa, Valentina

    2017-06-01

    Cornelia de Lange syndrome (CdLS) is an inherited condition with a wide spectrum of phenotypic anomalies, consisting mainly of growth impairment, multi-organ abnormalities, and neurocognitive delay. Clinical diagnostic criteria after birth are well defined, whereas when to suspect the syndrome during intrauterine life still remains undefined. This review summarizes the main possible prenatal findings in CdLS, suggesting that a skilled ultrasound scan in cases of intrauterine growth restriction associated with other fetal abnormalities may improve the chance of prenatal diagnosis of CdLS, especially in families known to be at high risk. We propose that, following a sequence of detailed scans and examinations, CdLS affected fetuses could be diagnosed in utero, when one or more conditions (among them, intrauterine growth restriction, limb defects, facial abnormalities, diaphragmatic hernia, and heart diseases) are detected, and possibly confirmed by specific molecular testing. Birth Defects Research 109:771-777, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

  6. Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

    PubMed

    Yuan, Bo; Pehlivan, Davut; Karaca, Ender; Patel, Nisha; Charng, Wu-Lin; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Sutton, V Reid; Yesil, Gozde; Bozdogan, Sevcan Tug; Tos, Tulay; Koparir, Asuman; Koparir, Erkan; Beck, Christine R; Gu, Shen; Aslan, Huseyin; Yuregir, Ozge Ozalp; Al Rubeaan, Khalid; Alnaqeb, Dhekra; Alshammari, Muneera J; Bayram, Yavuz; Atik, Mehmed M; Aydin, Hatip; Geckinli, B Bilge; Seven, Mehmet; Ulucan, Hakan; Fenercioglu, Elif; Ozen, Mustafa; Jhangiani, Shalini; Muzny, Donna M; Boerwinkle, Eric; Tuysuz, Beyhan; Alkuraya, Fowzan S; Gibbs, Richard A; Lupski, James R

    2015-02-01

    Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be "transcriptomopathies" rather than cohesinopathies.

  7. Recognition of the Cornelia de Lange syndrome phenotype with facial dysmorphology novel analysis.

    PubMed

    Basel-Vanagaite, L; Wolf, L; Orin, M; Larizza, L; Gervasini, C; Krantz, I D; Deardoff, M A

    2016-05-01

    Facial analysis systems are becoming available to healthcare providers to aid in the recognition of dysmorphic phenotypes associated with a multitude of genetic syndromes. These technologies automatically detect facial points and extract various measurements from images to recognize dysmorphic features and evaluate similarities to known facial patterns (gestalts). To evaluate such systems' usefulness for supporting the clinical practice of healthcare professionals, the recognition accuracy of the Cornelia de Lange syndrome (CdLS) phenotype was examined with FDNA's automated facial dysmorphology novel analysis (FDNA) technology. In the first experiment, 2D facial images of CdLS patients with either an NIPBL or SMC1A gene mutation as well as non-CdLS patients which were assessed by dysmorphologists in a previous study were evaluated by the FDNA technology; the average detection rate of experts was 77% while the system's detection rate was 87%. In the second study, when a new set of NIPBL, SMC1A and non-CdLS patient photos was evaluated, the detection rate increased to 94%. The results from both studies indicated that the system's detection rate was comparable to that of dysmorphology experts. Therefore, utilizing such technologies may be a useful tool in a clinical setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Functional Brain Imaging in Cornelia de Lange Syndrome: Case Report and Literature review.

    PubMed

    Silva-Hernández, Frieda; Rodríguez-Cuadrado, Gloria I; Martin-Ruaigip, Ralph J; Barreras-Ávila, Lourdes; González-Chevere, Brenda; Valentin-Rivera, Roberto; Labat-Alvarez, Eduardo

    2015-01-01

    Functional brain imaging with brain single photon emission computer tomography (Brain SPECT) has been used for many years in the evaluation of multiple neuro-degenerative and neuro-developmental disorders. Brain SPECT is a nuclear medicine tomographic study performed with a lipophilic radiopharmaceutical labeled with 99mTc-pertechnetate. It is a cerebral perfusion agent that depicts the global and regional perfusion patterns in the cortical gray matter and subcortical structures. Cornelia de Lange syndrome (CdLS) is a rare neuro-developmental and genetic condition, associated to several malformations. There are a limited number of cases reported in the medical literature and few of them report neuro-radiological and/or neuro-pathologic abnormalities. We report a case of a 15 year old patient, clinically diagnosed at birth with CdLS, who presents limited anatomical findings on Computed Tomography and Magnetic Resonance Imaging. To the best of our knowledge, this is the first report of the Brain SPECT findings in this syndrome.

  9. Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes

    PubMed Central

    Yuan, Bo; Pehlivan, Davut; Karaca, Ender; Patel, Nisha; Charng, Wu-Lin; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Sutton, V. Reid; Yesil, Gozde; Bozdogan, Sevcan Tug; Tos, Tulay; Koparir, Asuman; Koparir, Erkan; Beck, Christine R.; Gu, Shen; Aslan, Huseyin; Yuregir, Ozge Ozalp; Al Rubeaan, Khalid; Alnaqeb, Dhekra; Alshammari, Muneera J.; Bayram, Yavuz; Atik, Mehmed M.; Aydin, Hatip; Geckinli, B. Bilge; Seven, Mehmet; Ulucan, Hakan; Fenercioglu, Elif; Ozen, Mustafa; Jhangiani, Shalini; Muzny, Donna M.; Boerwinkle, Eric; Tuysuz, Beyhan; Alkuraya, Fowzan S.; Gibbs, Richard A.; Lupski, James R.

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be “transcriptomopathies” rather than cohesinopathies. PMID:25574841

  10. Identification of a novel de novo mutation in the NIPBL gene in an Iranian patient with Cornelia de Lange syndrome: A case report.

    PubMed

    Galehdari, Hamid; Monajemzadeh, Roya; Nazem, Habibolah; Mohamadian, Gholamreza; Pedram, Mohammad

    2011-06-27

    Cornelia de Lange syndrome is characterized by dysmorphic facial features, hirsutism, severe growth and developmental delay. Germline mutations in the NIPBL gene with an autosomal dominant pattern and in the SMC1A gene with an X-linked pattern have been identified in Cornelia de Lange syndrome. A two-month-old Iranian boy who showed multiple congenital anomalies was referred to the genetic center of a welfare organization in southwest Iran. He was the second child of a non-consanguineous marriage, born after full term with normal delivery. His birth weight was 3110 g, his length was 46 cm and his head circumference was 30 cm. Both parents were clinically asymptomatic, with no positive history of any deformity in their respective families. Sequencing of the NIPBL gene from our patient revealed a single-base deletion of thymidine in exon 10 (c.516delT). This mutation presumably results in premature termination at codon 526. We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome. The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome.

  11. Identification of a novel de novo mutation in the NIPBL gene in an Iranian patient with Cornelia de Lange syndrome: A case report

    PubMed Central

    2011-01-01

    Background Cornelia de Lange syndrome is characterized by dysmorphic facial features, hirsutism, severe growth and developmental delay. Germline mutations in the NIPBL gene with an autosomal dominant pattern and in the SMC1A gene with an X-linked pattern have been identified in Cornelia de Lange syndrome. Case presentation A two-month-old Iranian boy who showed multiple congenital anomalies was referred to the genetic center of a welfare organization in southwest Iran. He was the second child of a non-consanguineous marriage, born after full term with normal delivery. His birth weight was 3110 g, his length was 46 cm and his head circumference was 30 cm. Both parents were clinically asymptomatic, with no positive history of any deformity in their respective families. Conclusions Sequencing of the NIPBL gene from our patient revealed a single-base deletion of thymidine in exon 10 (c.516delT). This mutation presumably results in premature termination at codon 526. We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome. The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome. PMID:21707975

  12. Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3.

    PubMed

    Infante, Elena; Alkorta-Aranburu, Gorka; El-Gharbawy, Areeg

    2017-08-01

    Clinical features are variable in patients with Cornelia de Lange syndrome (CdLS). Milder forms exist with structural maintenance of chromosomes 3 (SMC3) mutations. Inherited milder forms of CdLS are uncommon and may be missed if genetic testing is limited to Nipped-B-like protein (NIPBL) and SMC1A. Parental studies should be pursued if there is a history of learning disabilities and/or dysmorphic features.

  13. A Comparative Study of Sociability in Angelman, Cornelia de Lange, Fragile X, Down and Rubinstein Taybi Syndromes and Autism Spectrum Disorder.

    PubMed

    Moss, Joanna; Nelson, Lisa; Powis, Laurie; Waite, Jane; Richards, Caroline; Oliver, Chris

    2016-11-01

    Few comparative studies have evaluated the heterogeneity of sociability across a range of neurodevelopmental disorders. The Sociability Questionnaire for People with Intellectual Disability (SQID) was completed by caregivers of individuals with Cornelia de Lange (n = 98), Angelman (n = 66), Fragile X (n = 142), Down (n = 117) and Rubinstein Taybi (n = 88) syndromes and autism spectrum disorder (ASD; n = 107). Between groups and age-band (<12yrs; 12-18yrs; >18yrs) comparisons of SQID scores were conducted. Rates of behaviors indicative of selective mutism were also examined. Fragile X syndrome achieved the lowest SQID scores. Cornelia de Lange, ASD, and Fragile X groups scored significantly lower than Angelman, Down and Rubinstein Taybi groups. Selective mutism characteristics were highest in Cornelia de Lange (40%) followed by Fragile X (17.8%) and ASD (18.2%). Age-band differences were identified in Cornelia de Lange and Down syndrome.

  14. Investigation of autistic features among individuals with mild to moderate Cornelia de Lange syndrome.

    PubMed

    Nakanishi, Mariko; Deardorff, Matthew A; Clark, Dinah; Levy, Susan E; Krantz, Ian; Pipan, Mary

    2012-08-01

    Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Autism has been reported to occur frequently in CdLS, but the frequency of autism in individuals with the milder CdLS phenotype is not well studied. We investigated autistic features by using a screening tool and a diagnostic interview in 49 individuals with the mild to moderate phenotype from a CdLS research database at the Children's Hospital of Philadelphia. The Social Communication Questionnaire (SCQ), a screening instrument for autistic disorder, was completed for all individuals. For individuals who screened positive and a subset of those that screened negative, the Autism Diagnostic Interview-Revised (ADI-R) was administered. Autistic symptom severity was not significantly different by gender, age groups, and genotypes. There was a significant correlation between higher levels of adaptive functioning and lower scores of autistic symptoms. The estimated prevalence of significant autistic features by ADI-R criteria was 43% in our cohort of individuals with the mild to moderate CdLS phenotype, which suggests that prevalence of autistic disorder may be higher than previously described among individuals with mild to moderate phenotype of CdLS. Clinicians who take care of individuals with CdLS should have a high index of suspicion for autistic features, and refer for further evaluation when these features are present in order to expedite appropriate intervention.

  15. Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts

    PubMed Central

    Pistocchi, A; Fazio, G; Cereda, A; Ferrari, L; Bettini, L R; Messina, G; Cotelli, F; Biondi, A; Selicorni, A; Massa, V

    2013-01-01

    Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the ‘cohesin complex'. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death. PMID:24136230

  16. Spectrum of NIPBL gene mutations in Polish patients with Cornelia de Lange syndrome.

    PubMed

    Kuzniacka, Alina; Wierzba, Jolanta; Ratajska, Magdalena; Lipska, Beata S; Koczkowska, Magdalena; Malinowska, Monika; Limon, Janusz

    2013-02-01

    Cornelia de Lange syndrome (CdLS) is a rare multi-system genetic disorder characterised by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. The disease is caused by mutations in genes responsible for the formation and regulation of cohesin complex. About half of the cases result from mutations in the NIPBL gene coding delangin, a protein regulating the initialisation of cohesion. To date, approximately 250 point mutations have been identified in more than 300 CdLS patients worldwide. In the present study, conducted on a group of 64 unrelated Polish CdLS patients, 25 various NIPBL sequence variants, including 22 novel point mutations, were detected. Additionally, large genomic deletions on chromosome 5p13 encompassing the NIPBL gene locus were detected in two patients with the most severe CdLS phenotype. Taken together, 42 % of patients were found to have a deleterious alteration affecting the NIPBL gene, by and large private ones (89 %). The review of the types of mutations found so far in Polish patients, their frequency and correlation with the severity of the observed phenotype shows that Polish CdLS cases do not significantly differ from other populations.

  17. Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts.

    PubMed

    Pistocchi, A; Fazio, G; Cereda, A; Ferrari, L; Bettini, L R; Messina, G; Cotelli, F; Biondi, A; Selicorni, A; Massa, V

    2013-10-17

    Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the 'cohesin complex'. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.

  18. Compromised Structure and Function of HDAC8 Mutants Identified in Cornelia de Lange Syndrome Spectrum Disorders

    PubMed Central

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly disorder resulting from mutations in genes that encode the core components of the cohesin complex, SMC1A, SMC3, and RAD21, or two of its regulatory proteins, NIPBL and HDAC8. HDAC8 is the human SMC3 lysine deacetylase required for cohesin recycling in the cell cycle. To date, 16 different missense mutations in HDAC8 have recently been identified in children diagnosed with CdLS. To understand the molecular effects of these mutations in causing CdLS and overlapping phenotypes, we have fully characterized the structure and function of five HDAC8 mutants: C153F, A188T, I243N, T311M, and H334R. X-ray crystal structures reveal that each mutation causes local structural changes that compromise catalysis and/or thermostability. For example, the C153F mutation triggers conformational changes that block acetate product release channels, resulting in only 2% residual catalytic activity. In contrast, the H334R mutation causes structural changes in a polypeptide loop distant from the active site and results in 91% residual activity, but the thermostability of this mutant is significantly compromised. Strikingly, the catalytic activity of these mutants can be partially or fully rescued in vitro by the HDAC8 activator N-(phenylcarbamothioyl)benzamide. These results suggest that HDAC8 activators might be useful leads in the search for new therapeutic strategies in managing CdLS. PMID:25075551

  19. Hidden mutations in Cornelia de Lange syndrome limitations of sanger sequencing in molecular diagnostics.

    PubMed

    Braunholz, Diana; Obieglo, Carolin; Parenti, Ilaria; Pozojevic, Jelena; Eckhold, Juliane; Reiz, Benedikt; Braenne, Ingrid; Wendt, Kerstin S; Watrin, Erwan; Vodopiutz, Julia; Rieder, Harald; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a well-characterized developmental disorder. The genetic cause of CdLS is a mutation in one of five associated genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) accounting for about 70% of cases. To improve our current molecular diagnostic and to analyze some of CdLS candidate genes, we developed and established a gene panel approach. Because recent data indicate a high frequency of mosaic NIPBL mutations that were not detected by conventional sequencing approaches of blood DNA, we started to collect buccal mucosa (BM) samples of our patients that were negative for mutations in the known CdLS genes. Here, we report the identification of three mosaic NIPBL mutations by our high-coverage gene panel sequencing approach that were undetected by classical Sanger sequencing analysis of BM DNA. All mutations were confirmed by the use of highly sensitive SNaPshot fragment analysis using DNA from BM, urine, and fibroblast samples. In blood samples, we could not detect the respective mutation. Finally, in fibroblast samples from all three patients, Sanger sequencing could identify all the mutations. Thus, our study highlights the need for highly sensitive technologies in molecular diagnostic of CdLS to improve genetic diagnosis and counseling of patients and their families. © 2014 WILEY PERIODICALS, INC.

  20. Two novel NIPBL gene mutations in Chinese patients with Cornelia de Lange syndrome.

    PubMed

    Mei, Libin; Liang, Desheng; Huang, Yanru; Pan, Qian; Wu, Lingqian

    2015-01-25

    Cornelia de Lange syndrome (CdLS) is a dominantly inherited developmental disorder characterized by distinctive facial features, mental retardation, and upper limb defects, with the involvement of multiple organs and systems. To date, mutations have been identified in five genes responsible for CdLS: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Here, we present a clinical and molecular characterization of five unrelated Chinese patients whose clinical presentation is consistent with that of CdLS. There were no chromosomal abnormalities in the five children. In three patients, DNA sequencing revealed a previously reported frameshift mutation c.2479delA (p.Arg827GlyfsX20), and two novel mutations including a heterozygous mutation c.6272 G>T (p.Cys2091Phe) and a frameshift mutation c.1672delA (p.Thr558LeufsX7) in NIPBL. For the remaining patients, large deletions and/or duplications within the NIPBL gene were excluded as playing a role in the pathogenesis, by Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. These findings broaden the mutation spectrum of NIPBL and further our understanding of the diverse and variable effects of NIPBL mutations on CdLS. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Congenital Heart Disease in Cornelia de Lange Syndrome: Phenotype and Genotype Analysis

    PubMed Central

    Chatfield, Kathryn C.; Schrier, Samantha A.; Li, Jennifer; Clark, Dinah; Kaur, Maninder; Kline, Antonie D.; Deardorff, Matthew A.; Jackson, Laird S.; Goldmuntz, Elizabeth; Krantz, Ian D.

    2013-01-01

    Congenital heart disease (CHD) has been reported to occur in 14–70% of individuals with Cornelia de Lange syndrome (CdLS, OMIM 122470) and accounts for significant morbidity and mortality when present. Charts from a cohort of 479 patients with CdLS were reviewed for cardiac evaluations, gene testing and information to determine phenotypic severity. Two hundred fifty-nine individuals had either documented structural defects or minor cardiac findings. The presence of CHD was then quantified as a function of mutation status and severity of CdLS: mild, moderate, or severe. Different types of CHD were also evaluated by mutation status to assess for any genotype –phenotype correlation. NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have CHD, although the number of SMC1A and SMC3 mutation-positive patients were small in comparison. Structural CHDs were more likely to be present in individuals with moderate and severe CdLS than in the mild phenotype. This study evaluates the trends of CHD seen in the CdLS population and correlates these findings with genotype. PMID:22965847

  2. Rare cerebrovascular anomalies in a patient with Cornelia De Lange Syndrome.

    PubMed

    Jones, Jesse; Duckwiler, Gary; Tateshima, Satoshi

    2015-01-01

    Cornelia De Lange (CDL) is a rare genetic syndrome characterized by short stature, intellectual disability, skeletal abnormalities, and distinctive facial features. We present a case of CDL with several rare cerebrovascular anatomic variants that impacted the treatment of a direct cavernous carotid fistula (CCF). This 32-year-old male CDL patient suffered a direct, traumatic CCF on the left and presented to our institution for endovascular management. Cerebral angiography revealed several anatomic variants, including hypoplastic external carotid arteries bilaterally. The vascular territory typically supplied by the internal maxillary arteries was fed by a prominent vessel arising from the internal carotid artery (ICA) in the expected location of the vidian artery. This anatomic variant directly impacted management due to retrograde filling of the fistula, necessitating coil embolization at its origin from the left ICA. Advance knowledge of cerebrovascular variants associated with CDL may help interventionalists prepare to approach such cases. Additionally, further inquiry into the function of proteins encoded by genes associated with CDL could better our understanding of vascular development in the brain.

  3. Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome.

    PubMed

    Mannini, Linda; Cucco, Francesco; Quarantotti, Valentina; Krantz, Ian D; Musio, Antonio

    2013-12-01

    Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. Clinical features include growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. The increased understanding of the genetic basis of CdLS has led to diagnostic improvement and expansion of the phenotype. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. Approximately 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. To date, 311 CdLS-causing mutations are known including missense, nonsense, small deletions and insertions, splice site mutations, and genomic rearrangements. Phenotypic variability is seen both intra- and intergenically. This article reviews the spectrum of CdLS mutations with a particular emphasis on their correlation to the clinical phenotype. © 2013 WILEY PERIODICALS, INC.

  4. Nucleotide sequence analysis of NIPBL gene in Indian Cornelia de Lange syndrome cases.

    PubMed

    Bajaj, Shailesh; Ranade, Suvidya; Gambhir, Prakash

    2013-01-01

    Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder in children. The disorder is caused mainly due to mutations in Nipped-B-like protein. The molecular data for CdLS is available from developed countries, but not available in developing countries like India. In the present study, the hotspot region of NIPBL gene was screened by Polymerase Chain Reaction which includes exon 2, 22, 42, and a biggest exon 10, in six CdLS patients and ten controls. The method adopted in present study was amplification of the target exon by using polymerase chain reaction, qualitative confirmation of amplicons by Agarose Gel Electrophoresis and use of amplicons for Conformation Sensitive Gel Electrophoresis to find heteroduplex formation followed by sequencing. We report two polymorphisms in the studied region of gene NIPBL. The polymorphisms are in the region of intron 1 and in exon 10. The polymorphism C/A is present in intron 1 region and polymorphism T/G in exon 10. The intronic region polymorphism may have a role in intron splicing whereas the polymorphism in exon 10 results in amino acid change (Val to Gly). These polymorphisms are disease associated as these are found in CdLS patients only and not in controls.

  5. Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally.

    PubMed

    Dempsey, M A; Knight Johnson, A E; Swope, B S; Moldenhauer, J S; Sroka, H; Chong, K; Chitayat, D; Briere, L; Lyon, H; Palmer, N; Gopalani, S; Siebert, J R; Lévesque, S; Leblanc, J; Menzies, D; Haverfield, E; Das, S

    2014-02-01

    Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia. CdLS has also been associated with decreased PAPP-A and increased nuchal translucency (NT). We reviewed NIPBL sequence analysis results for 12 prenatal samples in our laboratory to determine the frequency of mutations in our cohort. This retrospective study analyzed data from all 12 prenatal cases with suspected CdLS, which were received by The University of Chicago Genetic Services Laboratories. Diagnostic NIPBL sequencing was performed for all samples. Clinical information was collected from referring physicians. NIPBL mutations were identified in 9 out of the 12 cases prenatally (75%). Amongst the NIPBL mutation-positive cases with clinical information available, the most common findings were upper limb malformations and micrognathia. Five patients had NT measurements in the first trimester, of which four were noted to be increased. We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations. © 2013 John Wiley & Sons, Ltd.

  6. Connected Gene Communities Underlie Transcriptional Changes in Cornelia de Lange Syndrome.

    PubMed

    Boudaoud, Imène; Fournier, Éric; Baguette, Audrey; Vallée, Maxime; Lamaze, Fabien C; Droit, Arnaud; Bilodeau, Steve

    2017-09-01

    Cornelia de Lange syndrome (CdLS) is a complex multisystem developmental disorder caused by mutations in cohesin subunits and regulators. While its precise molecular mechanisms are not well defined, they point toward a global deregulation of the transcriptional gene expression program. Cohesin is associated with the boundaries of chromosome domains and with enhancer and promoter regions connecting the three-dimensional genome organization with transcriptional regulation. Here, we show that connected gene communities, structures emerging from the interactions of noncoding regulatory elements and genes in the three-dimensional chromosomal space, provide a molecular explanation for the pathoetiology of CdLS associated with mutations in the cohesin-loading factor NIPBL and the cohesin subunit SMC1A NIPBL and cohesin are important constituents of connected gene communities that are centrally positioned at noncoding regulatory elements. Accordingly, genes deregulated in CdLS are positioned within reach of NIPBL- and cohesin-occupied regions through promoter-promoter interactions. Our findings suggest a dynamic model where NIPBL loads cohesin to connect genes in communities, offering an explanation for the gene expression deregulation in the CdLS. Copyright © 2017 by the Genetics Society of America.

  7. Adolescents and adults affected by Cornelia de Lange syndrome: A report of 73 Italian patients.

    PubMed

    Mariani, Milena; Decimi, Valentina; Bettini, Laura Rachele; Maitz, Silvia; Gervasini, Cristina; Masciadri, Maura; Ajmone, Paola; Kullman, Gaia; Dinelli, Marco; Panceri, Roberto; Cereda, Anna; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex related genes. Its natural history is quite well characterized as regard pediatric age. Relatively little information is available regarding the evolution of the disease in young-adult age. In medical literature, only one specific study has been published on this topic. We report on our experience on 73 Italian CdLS patients (40 males and 33 females) with and age range from 15 to 49 years. Our results confirm the previous study indicating that gastroesophageal reflux disease (GERD) is the main medical problem of these patients in childhood and young-adult age. Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs' length, epilepsy, hearing, and visual problems. Behavioral problems are particularly frequent as well. For this reason, every source of hidden pain should be actively searched for in evaluating a patient showing such a disorder. Finally, recommendations for medical follow-up in adult age are discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Structural aspects of HDAC8 mechanism and dysfunction in Cornelia de Lange syndrome spectrum disorders.

    PubMed

    Deardorff, Matthew A; Porter, Nicholas J; Christianson, David W

    2016-11-01

    Cornelia de Lange Syndrome (CdLS) encompasses a broad spectrum of phenotypes characterized by distinctive craniofacial abnormalities, limb malformations, growth retardation, and intellectual disability. CdLS spectrum disorders are referred to as cohesinopathies, with ∼70% of patients having a mutation in a gene encoding a core cohesin protein (SMC1A, SMC3, or RAD21) or a cohesin regulatory protein (NIPBL or HDAC8). Notably, the regulatory function of HDAC8 in cohesin biology has only recently been discovered. This Zn(2+) -dependent hydrolase catalyzes the deacetylation of SMC3, a necessary step for cohesin recycling during the cell cycle. To date, 23 different missense mutants in the gene encoding HDAC8 have been identified in children with developmental features that overlap those of CdLS. Enzymological, biophysical, and structural studies of CdLS HDAC8 protein mutants have yielded critical insight on compromised catalysis in vitro. Most CdLS HDAC8 mutations trigger structural changes that directly or indirectly impact substrate binding and catalysis. Additionally, several mutations significantly compromise protein thermostability. Intriguingly, catalytic activity in many HDAC8 mutants can be partially or fully restored by an N-acylthiourea activator, suggesting a plausible strategy for the chemical rescue of compromised HDAC8 catalysis in vivo. © 2016 The Protein Society.

  9. NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype–phenotype correlation

    PubMed Central

    Pehlivan, Davut; Hullings, Melanie; Carvalho, Claudia M.B.; Gonzaga-Jauregui, Claudia G.; Loy, Elizabeth; Jackson, Laird G.; Krantz, Ian D.; Deardorff, Matthew A.; Lupski, James R.

    2013-01-01

    Purpose Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by mental retardation, limb abnormalities, distinctive facial features, and hirsutism. Mutations in three genes involved in sister chromatid cohesion, NIPBL, SMC1A, and SMC3, account for ~55% of CdLS cases. The molecular etiology of a significant fraction of CdLS cases remains unknown. We hypothesized that large genomic rearrangements of cohesin complex subunit genes may play a role in the molecular etiology of this disorder. Methods Custom high-resolution oligonucleotide array comparative genomic hybridization analyses interrogating candidate cohesin genes and breakpoint junction sequencing of identified genomic variants were performed. Results Of the 162 patients with CdLS, for whom mutations in known CdLS genes were previously negative by sequencing, deletions containing NIPBL exons were observed in 7 subjects (~5%). Breakpoint sequences in five patients implicated microhomology-mediated replicative mechanisms—such as serial replication slippage and fork stalling and template switching/microhomology-mediated break-induced replication—as a potential predominant contributor to these copy number variations. Most deletions are predicted to result in haploinsuflciency due to heterozygous loss-of-function mutations; such mutations may result in a more severe CdLS phenotype. Conclusion Our findings suggest a potential clinical utility to testing for copy number variations involving NIPBL when clinically diagnosed CdLS cases are mutation-negative by DNA-sequencing studies. PMID:22241092

  10. Mutation Spectrum and Genotype–Phenotype Correlation in Cornelia de Lange Syndrome

    PubMed Central

    Mannini, Linda; Cucco, Francesco; Quarantotti, Valentina; Krantz, Ian D.; Musio, Antonio

    2013-01-01

    Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. Clinical features include growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. The increased understanding of the genetic basis of CdLS has led to diagnostic improvement and expansion of the phenotype. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. Approximately 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. To date, 311 CdLS-causing mutations are known including missense, nonsense, small deletions and insertions, splice site mutations, and genomic rearrangements. Phenotypic variability is seen both intra- and intergenically. This article reviews the spectrum of CdLS mutations with a particular emphasis on their correlation to the clinical phenotype. PMID:24038889

  11. Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral characteristics and changes with age.

    PubMed

    Moss, Joanna; Penhallow, Jessica; Ansari, Morad; Barton, Stephanie; Bourn, David; FitzPatrick, David R; Goodship, Judith; Hammond, Peter; Roberts, Catherine; Welham, Alice; Oliver, Chris

    2017-06-01

    Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype-phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS. © 2017 Wiley Periodicals, Inc.

  12. Mutant cohesin affects RNA polymerase II regulation in Cornelia de Lange syndrome.

    PubMed

    Mannini, Linda; C Lamaze, Fabien; Cucco, Francesco; Amato, Clelia; Quarantotti, Valentina; Rizzo, Ilaria M; Krantz, Ian D; Bilodeau, Steve; Musio, Antonio

    2015-11-19

    In addition to its role in sister chromatid cohesion, genome stability and integrity, the cohesin complex is involved in gene transcription. Mutations in core cohesin subunits SMC1A, SMC3 and RAD21, or their regulators NIPBL and HDAC8, cause Cornelia de Lange syndrome (CdLS). Recent evidence reveals that gene expression dysregulation could be the underlying mechanism for CdLS. These findings raise intriguing questions regarding the potential role of cohesin-mediated transcriptional control and pathogenesis. Here, we identified numerous dysregulated genes occupied by cohesin by combining the transcriptome of CdLS cell lines carrying mutations in SMC1A gene and ChIP-Seq data. Genome-wide analyses show that genes changing in expression are enriched for cohesin-binding. In addition, our results indicate that mutant cohesin impairs both RNA polymerase II (Pol II) transcription initiation at promoters and elongation in the gene body. These findings highlight the pivotal role of cohesin in transcriptional regulation and provide an explanation for the typical gene dysregulation observed in CdLS patients.

  13. A search for uniparental disomy associated with Cornelia de Lange syndrome and with spontaneous abortion

    SciTech Connect

    Smith, M.J.; Upadhyaya, M.; Clarke, A.

    1994-09-01

    Uniparental disomy (UPD) is the inheritance of a pair of homologous chromosomes from one parent with no corresponding homologue from the other, in an individual with an apparently normal karyotype. Polymorphic DNA markers for the appropriate chromosome will therefore lack alleles from the non-contributing parent. There may be pathological consequences of UPD if an imprinted gene(s) resides on the affected chromosome. A number of human developmental disorders of unknown etiology, including Cornelia de Lange syndrome (CdLS) and spontaneous abortion, may be caused by imprinted genes yet to be discovered. There are a number of reports of chromosome 3q rearrangements associated with CdLS, therefore excluding whole-chromosome 3 UPD as a cause in these patients. We are also examining DNA markers for all autosomes in a series of 42 karyotypically normal spontaneous abortions and their parents. To date, no UPD has been observed for chromosomes 3, 17, 20, 21 and 22. Further work is in progress, both here and using the DNA typing facilities at Geneathon, France.

  14. An experimental study of executive function and social impairment in Cornelia de Lange syndrome.

    PubMed

    Nelson, Lisa; Crawford, Hayley; Reid, Donna; Moss, Joanna; Oliver, Chris

    2017-09-11

    Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants' caregivers. Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully.

  15. Prenatal Profile of Cornelia de Lange Syndrome (CdLS): A Review of 53 Pregnancies

    PubMed Central

    Clark, Dinah M.; Sherer, Ilana; Deardorff, Matthew A.; Byrne, Janice L.B.; Loomes, Kathleen M.; Nowaczyk, Malgorzata J.M.; Jackson, Laird G.; Krantz, Ian D.

    2012-01-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder characterized by growth retardation, cognitive impairment, external and internal structural malformations, and characteristic facial features. Currently, there are no definitive prenatal screening measures that lead to the diagnosis of CdLS. In this study, documented prenatal findings in CdLS syndrome were analyzed towards the development of a prenatal profile predictive of CdLS. We reviewed 53 cases of CdLS (29 previously reported and 24 unreported) in which prenatal observations/findings were available. The review of these cases revealed a pattern of sonographic findings, including obvious associated structural defects, growth restriction, as well as a more subtle, but strikingly characteristic, facial profile, suggestive of a recognizable prenatal ultrasonographic profile for CdLS. In addition the maternal serum marker, PAPP-A, may be reduced and fetal nuchal translucency may be increased in some pregnancies when measured at an appropriate gestational age. In conclusion, CdLS can be prenatally diagnosed or readily ruled out in a family with a known mutation in a CdLS gene. The characteristic ultrasonographic profile may allow for prenatal diagnosis of CdLS in 1) subsequent pregnancies to a couple with a prior child with CdLS in whom a mutation has not been identified or 2) when there are unexplained pregnancy signs of fetal abnormality such as oligo- or polyhydramnios, a low maternal serum PAPP-A level and/or increased nuchal translucency, fetal growth retardation, or structural anomalies consistent with CdLS. PMID:22740382

  16. An interstitial deletion of 8q23.3-q24.22 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and epilepsy.

    PubMed

    Chen, Chih-Ping; Lin, Shuan-Pei; Liu, Yu-Peng; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Chen, Yu-Ting; Lee, Chen-Chi; Wang, Wayseen

    2013-10-15

    We present a 19-year-old male with laxity of skin and joints, sparse scalp hair, facial dysmorphism, epilepsy, multiple exostoses, scoliosis, gastroesophageal reflux, cardiovascular defects, and an 8q23.3-q24.22 deletion detected by array comparative genomic hybridization. The patient was previously misdiagnosed as having Ehlers-Danlos syndrome. However, his clinical findings are in fact correlated with trichorhinophalangeal syndrome type II/Langer-Giedion syndrome and Cornelia de Lange syndrome-4. We discuss the genotype-phenotype correlation and the consequence of haploinsufficiency of TRPS1, RAD21, EXT1 and KCNQ3 in this case. © 2013.

  17. Autism traits in children and adolescents with Cornelia de Lange syndrome.

    PubMed

    Srivastava, Siddharth; Landy-Schmitt, Colleen; Clark, Bennett; Kline, Antonie D; Specht, Matt; Grados, Marco A

    2014-06-01

    Cornelia de Lange syndrome (CdLS) is a cohesinopathy causing delayed growth and limb deficits. Individuals with CdLS have mild to profound intellectual disability and autistic features. This study characterizes the behavioral phenotype of children with CdLS, focusing on autistic features, maladaptive behaviors, and impact of age. Children with CdLS (5-18 years) were administered normed instruments to characterize autism features (Childhood Autism Rating Scale, CARS), maladaptive behaviors (Aberrant Behavior Checklist), and adaptive skills (Vineland Adaptive Behaviors Scales). CdLS features and severity were rated with Diagnostic Criteria for CdLS. Forty-one children with CdLS (23 females, 18 males) were classified as having "no autism" (n = 7; 17.1%), "mild autism" (n = 17; 41.4%), and "severe autism" (n = 17; 41.4%), using CARS scores. Characteristic items were abnormal emotional response, stereotypies, odd object use, rigidity, lack of verbal communication, and low intellectual functioning. Verbal communication deficits and repetitive behaviors were higher compared to sensory, social cognition, and behavior abnormalities (P ≤ 0.0001). Maladaptive behaviors associated with autism traits were stereotypies (P = 0.003), hyperactivity (P = 0.01), and lethargy (P = 0.03). Activities of daily living were significantly affected; socialization adaptive skills were a relative strength. However, with advancing age, both socialization (P < 0.0001) and communication (P = 0.001) domains declined significantly. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. While other adaptive skills are impacted, socialization adaptive skills are less affected. Advancing age can worsen communication and socialization deficits relative to neurotypical peers. © 2014 Wiley Periodicals, Inc.

  18. Biochemical and Structural Characterization of HDAC8 Mutants Associated with Cornelia de Lange Syndrome Spectrum Disorders

    PubMed Central

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) spectrum disorders are characterized by multiple organ system congenital anomalies that result from mutations in genes encoding core cohesin proteins SMC1A, SMC3, and RAD21, or proteins that regulate cohesin function such as NIPBL and HDAC8. HDAC8 is the Zn2+-dependent SMC3 deacetylase required for cohesin recycling during the cell cycle, and 17 different HDAC8 mutants have been identified to date in children diagnosed with CdLS. As part of our continuing studies focusing on aberrant HDAC8 function in CdLS, we now report the preparation and biophysical evaluation of five human HDAC8 mutants: P91L, G117E, H180R, D233G, and G304R. Additionally, the double mutants D233G–Y306F and P91L–Y306F were prepared to enable cocrystallization of intact enzyme–substrate complexes. X-ray crystal structures of G117E, P91L–Y306F, and D233G–Y306F HDAC8 mutants reveal that each CdLS mutation causes structural changes that compromise catalysis and/or thermostability. For example, the D233G mutation disrupts the D233–K202–S276 hydrogen bond network, which stabilizes key tertiary structure interactions, thereby significantly compromising thermostability. Molecular dynamics simulations of H180R and G304R HDAC8 mutants suggest that the bulky arginine side chain of each mutant protrudes into the substrate binding site and also causes active site residue Y306 to fluctuate away from the position required for substrate activation and catalysis. Significantly, the catalytic activities of most mutants can be partially or fully rescued by the activator N-(phenylcarbamothioyl)-benzamide, suggesting that HDAC8 activators may serve as possible leads in the therapeutic management of CdLS. PMID:26463496

  19. Sedation and general anesthesia for patients with Cornelia De Lange syndrome: A case series.

    PubMed

    Moretto, Alessandra; Scaravilli, Vittorio; Ciceri, Valentina; Bosatra, Mariagrazia; Giannatelli, Federica; Ateniese, Bianca; Mariani, Milena; Cereda, Anna; Sosio, Simone; Zanella, Alberto; Pesenti, Antonio; Selicorni, Angelo

    2016-06-01

    Cornelia De Lange syndrome (CdLS) is a rare congenital disease characterized by typical facial dysmorphism, developmental disability, and limb deficiency defects. Various congenital malformations and medical complications have been described with gastroesophageal reflux as the major one. CdLS patients often require multiple high-risk anesthetic procedures. At San Gerardo Hospital (Monza, Italy) the management of CdLS patients is routinely organized through a standard protocol and a dedicated pediatric anesthesia team has been implemented. We report on a retrospective descriptive analysis of the anesthetic records of the CdLS patients admitted to San Gerardo Hospital from January 2010 to December 2015. We retrieved: demographics, genetic profiles, type of procedures, anesthetic approaches, anesthetics usage and complications. Data are reported as median (interquartile range) values. Twenty-seven patients (11 female), with age 12 (7-15) years old, weight 24 (14-35) kg, and severity score of 25 (18-32) were included. NIBPL mutations were the most frequently represented. We analyzed 58 procedures (30 esophagogastroduodenoscopies, 8 evoked auditory potential tests, 5 radiodiagnostics, 5 catheters positioning, 4 bronchoscopies) managed by sedation (36) and general anesthesia (6). Each patient underwent one (1-2) anesthetic procedure. Propofol (59%), sevoflurane (31%), fentanyl (24%), and ketamine (10%) were used. Three out of six endotracheal intubations were difficult. The only documented intraoperative complications were three episodes of desaturation (oxygen saturation <90%) occurring during sedations and were managed without the need for an invasive control of the airways. Implementation of a specific management protocol and a dedicated allowed to provide anesthesia to CdLS patients without the occurrence of major complications. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Biochemical and structural characterization of HDAC8 mutants associated with Cornelia de Lange syndrome spectrum disorders.

    PubMed

    Decroos, Christophe; Christianson, Nicolas H; Gullett, Laura E; Bowman, Christine M; Christianson, Karen E; Deardorff, Matthew A; Christianson, David W

    2015-10-27

    Cornelia de Lange Syndrome (CdLS) spectrum disorders are characterized by multiple organ system congenital anomalies that result from mutations in genes encoding core cohesin proteins SMC1A, SMC3, and RAD21, or proteins that regulate cohesin function such as NIPBL and HDAC8. HDAC8 is the Zn(2+)-dependent SMC3 deacetylase required for cohesin recycling during the cell cycle, and 17 different HDAC8 mutants have been identified to date in children diagnosed with CdLS. As part of our continuing studies focusing on aberrant HDAC8 function in CdLS, we now report the preparation and biophysical evaluation of five human HDAC8 mutants: P91L, G117E, H180R, D233G, and G304R. Additionally, the double mutants D233G-Y306F and P91L-Y306F were prepared to enable cocrystallization of intact enzyme-substrate complexes. X-ray crystal structures of G117E, P91L-Y306F, and D233G-Y306F HDAC8 mutants reveal that each CdLS mutation causes structural changes that compromise catalysis and/or thermostability. For example, the D233G mutation disrupts the D233-K202-S276 hydrogen bond network, which stabilizes key tertiary structure interactions, thereby significantly compromising thermostability. Molecular dynamics simulations of H180R and G304R HDAC8 mutants suggest that the bulky arginine side chain of each mutant protrudes into the substrate binding site and also causes active site residue Y306 to fluctuate away from the position required for substrate activation and catalysis. Significantly, the catalytic activities of most mutants can be partially or fully rescued by the activator N-(phenylcarbamothioyl)-benzamide, suggesting that HDAC8 activators may serve as possible leads in the therapeutic management of CdLS.

  1. Cornelia de Lange syndrome: Correlation of brain MRI findings with behavioral assessment.

    PubMed

    Roshan Lal, Tamanna R; Kliewer, Mark A; Lopes, Thelma; Rebsamen, Susan L; O'Connor, Julia; Grados, Marco A; Kimball, Amy; Clemens, Julia; Kline, Antonie D

    2016-06-01

    Neurobehavioral and developmental issues with a broad range of deficits are prominent features of Cornelia de Lange syndrome (CdLS), a disorder due to disruption of the cohesin protein complex. The etiologic relationship of these clinical findings to anatomic abnormalities on neuro-imaging studies has not, however, been established. Anatomic abnormalities in the brain and central nervous system specific to CdLS have been observed, including changes in the white matter, brainstem, and cerebellum. We hypothesize that location and severity of brain abnormalities correlate with clinical phenotype in CdLS, as seen in other developmental disorders. In this study, we retrospectively evaluated brain MRI studies of 15 individuals with CdLS and compared these findings to behavior at the time of the scan. Behavior was assessed using the Aberrant Behavior Checklist (ABC), a validated behavioral assessment tool with several clinical features. Ten of fifteen (67%) of CdLS patients had abnormal findings on brain MRI, including cerebral atrophy, white matter changes, cerebellar hypoplasia, and enlarged ventricles. Other findings included pituitary tumors or cysts, Chiari I malformation and gliosis. Abnormal behavioral scores in more than one behavioral area were seen in all but one patient. All 5 of the 15 (33%) patients with normal structural MRI studies had abnormal ABC scores. All normal ABC scores were noted in only one patient and this was correlated with moderately abnormal MRI changes. Although our cohort is small, our results suggest that abnormal behaviors can exist in individuals with CdLS in the setting of relatively normal structural brain findings. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Cornelia de Lange Syndrome: Correlation of Brain MRI Findings With Behavioral Assessment

    PubMed Central

    ROSHAN LAL, TAMANNA R.; KLIEWER, MARK A.; LOPES, THELMA; REBSAMEN, SUSAN L.; O’CONNOR, JULIA; GRADOS, MARCO A.; KIMBALL, AMY; CLEMENS, JULIA; KLINE, ANTONIE D.

    2017-01-01

    Neurobehavioral and developmental issues with a broad range of deficits are prominent features of Cornelia de Lange syndrome (CdLS), a disorder due to disruption of the cohesin protein complex. The etiologic relationship of these clinical findings to anatomic abnormalities on neuro-imaging studies has not, however, been established. Anatomic abnormalities in the brain and central nervous system specific to CdLS have been observed, including changes in the white matter, brainstem, and cerebellum. We hypothesize that location and severity of brain abnormalities correlate with clinical phenotype in CdLS, as seen in other developmental disorders. In this study, we retrospectively evaluated brain MRI studies of 15 individuals with CdLS and compared these findings to behavior at the time of the scan. Behavior was assessed using the Aberrant Behavior Checklist (ABC), a validated behavioral assessment tool with several clinical features. Ten of fifteen (67%) of CdLS patients had abnormal findings on brain MRI, including cerebral atrophy, white matter changes, cerebellar hypoplasia, and enlarged ventricles. Other findings included pituitary tumors or cysts, Chiari I malformation and gliosis. Abnormal behavioral scores in more than one behavioral area were seen in all but one patient. All 5 of the 15 (33%) patients with normal structural MRI studies had abnormal ABC scores. All normal ABC scores were noted in only one patient and this was correlated with moderately abnormal MRI changes. Although our cohort is small, our results suggest that abnormal behaviors can exist in individuals with CdLS in the setting of relatively normal structural brain findings. PMID:27164360

  3. Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts.

    PubMed

    Fazio, Grazia; Bettini, Laura Rachele; Rigamonti, Silvia; Meta, Dorela; Biondi, Andrea; Cazzaniga, Giovanni; Selicorni, Angelo; Massa, Valentina

    2017-07-28

    Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells. Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real-time polymerase chain reaction experiments. We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL-mutated patients and healthy donors, with or without RA treatment. In all cases, ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells. We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. The Incidence of Thrombocytopenia in Children with Cornelia de Lange Syndrome

    PubMed Central

    Lambert, Michele P.; Jackson, Laird G.; Clark, Dinah; Kaur, Mani; Krantz, Ian D.; Deardorff, Matthew A.

    2010-01-01

    Thrombocytopenia was first reported in Cornelia de Lange Syndrome (CdLS) by Froster in 1993. Despite early reports, thrombocytopenia has been rarely reported in this disorder. We performed a retrospective analysis of a large cohort of patients with CdLS. We calculated prevalence of thrombocytopenia in 3 subsets of this cohort: the entire cohort (n=1740), a subset of subjects with substantial clinical records (n=695) and a subset of subjects with clinical information regarding platelet counts (n=85). This analysis revealed that 15 have had thrombocytopenia (18% of those with available blood counts); seven had Immune ThrombocytoPenia (ITP). The reported prevalence of pediatric ITP is between 5-13 per 100,000 persons. The prevalence of ITP in this cohort is between 7/1740 and 7/85, giving a relative risk of ITP of between 30 (CI 12 to 77) and 633 (CI 259-1549). Contrary to the reported cases in the literature, none of our patients have had progression of the thrombocytopenia nor have they developed other cytopenias. All 15 patients with thromobocytopenia had CdLS based on clinical criteria. Of the 10 patients tested for mutations in NIBPL, eight had mutations identified. These data support an increased incidence of thrombocytopenia and ITP in CdLS. Subsequently, patients are at risk for spontaneous hemorrhage, and likely increased risk secondary to the high frequency of self-injurious behavior. Although further studies are needed to better define the scope of the problem and to define the mechanisms of thrombocytopenia in CdLS, we would recommend screening for thrombocytopenia upon diagnosis and at five-year intervals thereafter. PMID:21204208

  5. HDAC8 mutations in Cornelia de Lange Syndrome affect the cohesin acetylation cycle

    PubMed Central

    Deardorff, Matthew A.; Bando, Masashige; Nakato, Ryuichiro; Watrin, Erwan; Itoh, Takehiko; Minamino, Masashi; Saitoh, Katsuya; Komata, Makiko; Katou, Yuki; Clark, Dinah; Cole, Kathryn E.; Baere, Elfride De; Decroos, Christophe; Donato, Nataliya Di; Ernst, Sarah; Francey, Lauren J.; Gyftodimou, Yolanda; Hirashima, Kyotaro; Hullings, Melanie; Ishikawa, Yuuichi; Jaulin, Christian; Kaur, Maninder; Kiyono, Tohru; Lombardi, Patrick M.; Magnaghi-Jaulin, Laura; Mortier, Geert R.; Nozaki, Naohito; Petersen, Michael B.; Seimiya, Hiroyuki; Siu, Victoria M.; Suzuki, Yutaka; Takagaki, Kentaro; Wilde, Jonathan J.; Willems, Patrick J.; Prigent, Claude; Gillessen-Kaesbach, Gabriele; Christianson, David W.; Kaiser, Frank J.; Jackson, Laird G.; Hirota, Toru; Krantz, Ian D.; Shirahige, Katsuhiko

    2012-01-01

    Cornelia de Lange syndrome (CdLS) is a dominantly inherited congenital malformation disorder caused by mutations in the cohesin-loading protein NIPBL1,2 for nearly 60% of individuals with classical CdLS3-5 and in the core cohesin components SMC1A (~5%) and SMC3 (<1%) for a smaller fraction of probands6,7. In humans, the multi-subunit complex cohesin is comprised of SMC1, SMC3, RAD21 and a STAG protein to form a ring structure proposed to encircle sister chromatids to mediate sister chromatid cohesion (SCC)8 as well as play key roles in gene regulation9. SMC3 is acetylated during S-phase to establish cohesiveness of chromatin-loaded cohesin10-13 and in yeast, HOS1, a class I histone deacetylase, deacetylates SMC3 during anaphase14-16. Here we report the identification of HDAC8 as the vertebrate SMC3 deacetylase as well as loss-of-function HDAC8 mutations in six CdLS probands. Loss of HDAC8 activity results in increased SMC3 acetylation (SMC3-ac) and inefficient dissolution of the “used” cohesin complex released from chromatin in both prophase and anaphase. While SMC3 with retained acetylation is loaded onto chromatin, ChIP-Seq analysis demonstrates decreased occupancy of cohesin localization sites that results in a consistent pattern of altered transcription seen in CdLS cell lines with either NIPBL or HDAC8 mutations. PMID:22885700

  6. Characterization of limb differences in children with Cornelia de Lange Syndrome.

    PubMed

    Mehta, Devanshi; Vergano, Samantha A Schrier; Deardorff, Matthew; Aggarwal, Sarika; Barot, Akash; Johnson, Drew M; Miller, Nathan F; Noon, Sarah E; Kaur, Maninder; Jackson, Laird; Krantz, Ian D

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a well-described multisystem developmental disorder characterized by dysmorphic facial features, growth and behavioral deficits, and cardiac, gastrointestinal, and limb anomalies. The limb defects seen in CdLS can be mild, with small feet or hands only, or can be severe, with variable deficiency defects involving primarily the ulnar structures and ranging from mild hypoplasia of the fifth digit to complete absence of the forearm. Interestingly, the upper limbs are typically much more involved than the lower extremities that generally manifest with small feet and 2-3 syndactyly of the toes and shortened fourth metatarsal. The upper limbs often manifest asymmetric involvement. The limb findings in our cohort of 378 individuals with CdLS demonstrate a consistent pattern of laterality and symmetry involvement (with increased severity of right-sided limb in individuals with asymmetric limb defects) and a correlation of more significant limb defects with an increased risk of other structural anomalies, and more severe behavioral outcomes. Additionally, we found that individuals with mutations in NIPBL were most likely to have limb defects compared to mutations in other genes with nonsense, exonic deletion, and frameshift mutations being most prevalent in those with limb defects. Characterization of the limb differences in children with CdLS may provide a tool to assist in genetic counseling and determining prognosis. This paper will review the limb involvement in a large cohort of individuals with CdLS assessing the correlation with molecular etiologies, symmetry, additional structural birth defects, and cognitive outcomes. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Genetic Enhancement of Limb Defects in a Mouse Model of Cornelia de Lange Syndrome

    PubMed Central

    LOPEZ-BURKS, MARTHA E.; SANTOS, ROSAYSELA; KAWAUCHI, SHIMAKO; CALOF, ANNE L.; LANDER, ARTHUR D.

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is characterized by a wide variety of structural and functional abnormalities in almost every organ system of the body. CdLS is now known to be caused by mutations that disrupt the function of the cohesin complex or its regulators, and studies of animal models and cell lines tell us that the effect of these mutations is to produce subtle yet pervasive dysregulation of gene expression. With many hundreds of mostly small gene expression changes occurring in every cell type and tissue, identifying the etiology of any particular birth defect is very challenging. Here we focus on limb abnormalities, which are commonly seen in CdLS. In the limb buds of the Nipbl-haploinsufficient mouse (Nipbl+/− mouse), a model for the most common form of CdLS, modest gene expression changes are observed in several candidate pathways whose disruption is known to cause limb abnormalities, yet the limbs of Nipbl+/− mice develop relatively normally. We hypothesized that further impairment of candidate pathways might produce limb defects similar to those seen in CdLS, and performed genetic experiments to test this. Focusing on Sonic hedgehog (Shh), Bone morphogenetic protein (Bmp), and Hox gene pathways, we show that decreasing Bmp or Hox function (but not Shh function) enhances polydactyly in Nipbl+/− mice, and in some cases produces novel skeletal phenotypes. However, frank limb reductions, as are seen in a subset of individuals with CdLS, do not occur, suggesting that additional signaling and/or gene regulatory pathways are involved in producing such dramatic changes. PMID:27120109

  8. Drosophila Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior.

    PubMed

    Wu, Yaning; Gause, Maria; Xu, Dongbin; Misulovin, Ziva; Schaaf, Cheri A; Mosarla, Ramya C; Mannino, Elizabeth; Shannon, Megan; Jones, Emily; Shi, Mi; Chen, Wen-Feng; Katz, Olivia L; Sehgal, Amita; Jongens, Thomas A; Krantz, Ian D; Dorsett, Dale

    2015-11-01

    Individuals with Cornelia de Lange Syndrome (CdLS) display diverse developmental deficits, including slow growth, multiple limb and organ abnormalities, and intellectual disabilities. Severely-affected individuals most often have dominant loss-of-function mutations in the Nipped-B-Like (NIPBL) gene, and milder cases often have missense or in-frame deletion mutations in genes encoding subunits of the cohesin complex. Cohesin mediates sister chromatid cohesion to facilitate accurate chromosome segregation, and NIPBL is required for cohesin to bind to chromosomes. Individuals with CdLS, however, do not display overt cohesion or segregation defects. Rather, studies in human cells and model organisms indicate that modest decreases in NIPBL and cohesin activity alter the transcription of many genes that regulate growth and development. Sister chromatid cohesion factors, including the Nipped-B ortholog of NIPBL, are also critical for gene expression and development in Drosophila melanogaster. Here we describe how a modest reduction in Nipped-B activity alters growth and neurological function in Drosophila. These studies reveal that Nipped-B heterozygous mutant Drosophila show reduced growth, learning, and memory, and altered circadian rhythms. Importantly, the growth deficits are not caused by changes in systemic growth controls, but reductions in cell number and size attributable in part to reduced expression of myc (diminutive) and other growth control genes. The learning, memory and circadian deficits are accompanied by morphological abnormalities in brain structure. These studies confirm that Drosophila Nipped-B mutants provide a useful model for understanding CdLS, and provide new insights into the origins of birth defects.

  9. A longitudinal follow-up study of affect in children and adults with Cornelia de Lange syndrome.

    PubMed

    Nelson, Lisa; Moss, Jo; Oliver, Chris

    2014-05-01

    Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N  =  67), cri du chat syndrome (CdCS; N  =  42), and Fragile X syndrome (FXS; N  =  142) completed the Mood, Interest and Pleasure Questionnaire (MIPQ) at Time 1 and 2 years later (Time 2). Scores on the MIPQ were significantly lower in the CdLS group compared with the CdCS and FXS groups at Time 1 and Time 2. Lower MIPQ scores were characteristic of older adolescents (> 15 years) and adults with CdLS. However, there were no significant differences in MIPQ scores between Time 1 and Time 2. Age and insistence on sameness predicted MIPQ scores in CdLS.

  10. Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome

    PubMed Central

    2013-01-01

    Background Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant disorder characterised by facial dysmorphism, growth and psychomotor developmental delay and skeletal defects. To date, causative mutations in the NIPBL (cohesin regulator) and SMC1A (cohesin structural subunit) genes account for > 50% and 6% of cases, respectively. Methods We recruited 50 patients with a CdLS clinical diagnosis or with features that overlap with CdLS, who were negative for mutations at NIPBL and SMC1A at molecular screening. Chromosomal rearrangements accounting for the clinical diagnosis were screened for using array Comparative Genomic Hybridisation (aCGH). Results Four patients were shown to carry imbalances considered to be candidates for having pathogenic roles in their clinical phenotypes: patient 1 had a 4.2 Mb de novo deletion at chromosome 20q11.2-q12; patient 2 had a 4.8 Mb deletion at chromosome 1p36.23-36.22; patient 3 carried an unbalanced translocation, t(7;17), with a 14 Mb duplication of chromosome 17q24.2-25.3 and a 769 Kb deletion at chromosome 7p22.3; patient 4 had an 880 Kb duplication of chromosome 19p13.3, for which his mother, who had a mild phenotype, was also shown to be a mosaic. Conclusions Notwithstanding the variability in size and gene content of the rearrangements comprising the four different imbalances, they all map to regions containing genes encoding factors involved in cell cycle progression or genome stability. These functional similarities, also exhibited by the known CdLS genes, may explain the phenotypic overlap between the patients included in this study and CdLS. Our findings point to the complexity of the clinical diagnosis of CdLS and confirm the existence of phenocopies, caused by imbalances affecting multiple genomic regions, comprising 8% of patients included in this study, who did not have mutations at NIPBL and SMC1A. Our results suggests that analysis by aCGH should be recommended for CdLS spectrum cases with an

  11. Audiological findings, genotype and clinical severity score in Cornelia de Lange syndrome.

    PubMed

    Marchisio, Paola; Selicorni, Angelo; Bianchini, Sonia; Milani, Donatella; Baggi, Elena; Cerutti, Marta; Larizza, Lidia; Principi, Nicola; Esposito, Susanna

    2014-07-01

    Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder in which hearing loss (HL) has been reported. However, no data are available concerning the association between audiological findings, clinical severity score and genotype. The study involved 44 pediatric patients aged 1-18 years with a confirmed diagnosis of CdLS, all of whom underwent a full otolaryngological and audiological examination. The presence of NIPBL and SMC1 mutations was also evaluated. According to the severity of clinical phenotypes, 12 (27.3%) children were mild, 15 (34.1%) were moderate and 17 (38.6%) were severe. Thirty-eight children (86%) had OME. Eight children had normal hearing, including one (12.5%) with a severe phenotype. Bilateral sensorineural hearing loss (SNHL) was diagnosed in 10 children (22.7%): the degree of HL was severe in 8 (80%), all with a severe phenotype. Conductive hearing loss (CHL) was present in 26 patients (59.1%), of whom 8 (30.8%) had a severe phenotype. A severe phenotype was more prevalent among the patients with moderate to severe HL (10/16, 62.5%) than among those with slight/mild HL or normal hearing (7/28, 25.0% p=0.013). NIPBL mutations were detected in 22 patients (50%): 13 (59.1%) with truncating mutations, four (18.2%) with missense mutations, and five (22.7%) with splicing mutations. The frequency of NIPBL truncating mutations was similar in the children with SNHL and those with CHL, whereas this kind of mutation was not found in children with normal hearing. Together with SNHL, CHL is an important cause of HL in children with CdLS, and can be associated with a severe phenotype. Moreover, CHL can be associated with NIPBL mutations, particularly truncating mutations. These results highlight the importance of the early identification of audiological problems in children with CdLS and their precise genetic characterization. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Diverse Profiles of Anxiety Related Disorders in Fragile X, Cornelia de Lange and Rubinstein-Taybi Syndromes.

    PubMed

    Crawford, Hayley; Waite, Jane; Oliver, Chris

    2017-01-31

    Anxiety disorders are heightened in specific genetic syndromes in comparison to intellectual disability of heterogeneous aetiology. In this study, we described and contrasted anxiety symptomatology in fragile X (FXS), Cornelia de Lange (CdLS) and Rubinstein-Taybi syndromes (RTS), and compared the symptomatology to normative data for typically-developing children and children diagnosed with an anxiety disorder. Scores did not differ between children diagnosed with an anxiety disorder and (a) participants with FXS on social phobia, panic/agoraphobia, physical injury fears, and obsessive-compulsive subscales (b) participants with CdLS on separation anxiety, generalized anxiety, panic/agoraphobia, physical injury fears and obsessive-compulsive subscales, and (c) participants with RTS on panic/agoraphobia and obsessive-compulsive subscales. The results highlight divergent profiles of anxiety symptomatology between these groups.

  13. Challenges of caring for a patient with a rare disease--as demonstrated by Cornelia de Lange Syndrome.

    PubMed

    Wierzba, Jolanta; Mazurkiewicz-Bełdzińska, Maria; Jabłońska-Brudło, Joanna; Potaż, Piotr; Banach, Piotr

    2015-01-01

    There are over 12,500 diseases defined by European researchers as rare disorders occurring in less than 1:2000 live births. The majority of these manifest in childhood. The clinical picture of a rare disorder is dominated by intellectual disability of various severity and organ defects. Targeted therapy is not available for the majority of rare disorders, therefore multidisciplinary patient care is the only means of improving the quality and duration of the patient's life. In this paper, the authors share their experience organizing a system of care for patients with Cornelia de Lange Syndrome. Over the last 13 years, multidisciplinary diagnostics and consultations were provided to 92 patients and their families, including rehabilitation and psychological support. The model suggested here demonstrates a shorter diagnostic process, continuous contact with the patient, his/her family and pediatrician. Guidelines and recommendations regarding the particular rare disease should be published.

  14. Social behavior and characteristics of autism spectrum disorder in Angelman, Cornelia de Lange, and Cri du Chat syndromes.

    PubMed

    Moss, Joanna; Howlin, Patricia; Hastings, Richard Patrick; Beaumont, Sarah; Griffith, Gemma M; Petty, Jane; Tunnicliffe, Penny; Yates, Rachel; Villa, Darrelle; Oliver, Chris

    2013-07-01

    We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; n  =  19; mean age  = 10.35 years), Cornelia de Lange (CdLS; n  =  15; mean age  = 12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; n  =  19; mean age  =  8.80 years) syndromes. The proportion of individuals meeting the ASD cutoff on the Social Communication Questionnaire was significantly higher in the AS and CdLS groups than in the CdCS group (p < .01). The groups demonstrated divergent social behavior profiles during social conditions in which adult availability, adult familiarity, and social demand were manipulated. Social enjoyment was significantly heightened in AS, whereas social approaches were heightened in individuals with CdCS. Social motivation, social communication, and enjoyment were significantly lower in CdLS. The findings highlight the importance of detailed observation when evaluating ASD and social behavior in genetic syndromes.

  15. Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: comments on the article by Pereza et al. [2012].

    PubMed

    Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

    2015-06-01

    In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  16. Cornelia de Lange syndrome: further delineation of phenotype, cohesin biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts.

    PubMed

    Kline, Antonie D; Calof, Anne L; Schaaf, Cheri A; Krantz, Ian D; Jyonouchi, Soma; Yokomori, Kyoko; Gauze, Maria; Carrico, Cheri S; Woodman, Julie; Gerton, Jennifer L; Vega, Hugo; Levin, Alex V; Shirahige, Katsuhiko; Champion, Michele; Goodban, Marjorie T; O'Connor, Julia T; Pipan, Mary; Horsfield, Julia; Deardorff, Matthew A; Ishman, Stacey L; Dorsett, Dale

    2014-06-01

    Cornelia de Lange syndrome (CdLS) is the prototype for the cohesinopathy disorders that have mutations in genes associated with the cohesin subunit in all cells. Roberts syndrome is the next most common cohesinopathy. In addition to the developmental implications of cohesin biology, there is much translational and basic research, with progress towards potential treatment for these conditions. Clinically, there are many issues in CdLS faced by the individual, parents and caretakers, professionals, and schools. The following abstracts are presentations from the 5th Cornelia de Lange Syndrome Scientific and Educational Symposium on June 20-21, 2012, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting, Lincolnshire, IL. The research committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts and subsequently disseminates the information to the families. In addition to the basic science and clinical discussions, there were educationally-focused talks related to practical aspects of management at home and in school. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. © 2014 Wiley Periodicals, Inc.

  17. Communication, cognitive development and behavior in children with Cornelia de Lange Syndrome (CdLS): preliminary results.

    PubMed

    Ajmone, Paola Francesca; Rigamonti, Claudia; Dall'Ara, Francesca; Monti, Federico; Vizziello, Paola; Milani, Donatella; Cereda, Anna; Selicorni, Angelo; Costantino, Antonella

    2014-04-01

    In this study, we present preliminary data on cognitive, behavioral and communication domains of individuals with Cornelia de Lange Syndrome (CdLS), collected through a specific protocol combining direct and indirect tools. Seventeen subjects with CdLS were assessed, 2.5- to 13.4-year-old. Cognitive level of the subjects differed from what previously described in literature, showing more patients with normal or borderline cognitive abilities. We found a relation between severe autistic behavior and comprehension impairments: all children with high CARS score have severe receptive language disability. A correlation was also found between CARS score and ID: high CARS score occurred only in patients with profound levels of ID. Results of this study support the need for a specific assessment protocol tailored for the characteristics of subjects with multiple disabilities, to be able to identify their strengths avoiding the avalanche effect of weaknesses. Most tests on neuropsychological functions have been developed and standardized for typically developing children, and require the integrity of other functions aside the one that is evaluated, determining an underestimation of the level of functioning. This study could be a starting point to develop new models applicable to other genetic syndromes and complex situations; new and wider studies are needed in order to allow a more complete and accurate assessment, thereby ensuring more efficient and family-centered treatment plans. © 2014 Wiley Periodicals, Inc.

  18. A 6-year-old boy with Cornelia de Lange syndrome and Coats disease: case report and review of the literature.

    PubMed

    Stacey, Andrew W; Sparagna, Cristina; Borri, Melissa; Rizzo, Stanislao; Hadjistilianou, Theodora

    2015-10-01

    Cornelia de Lange syndrome (CdLS) can result in multiple congenital abnormalities and numerous ocular findings. We report the case of a 6-year-old boy with history of CdLS who presented with Coats disease. The findings in this case are compared to those found in the two previously reported cases of concomitant CdLS and Coats disease. The low incidence of these two disorders makes it highly unlikely that the connection is random in these 3 cases. The number of patients with both Cornelia de Lange syndrome and Coats disease is likely underestimated due to the difficulty in examining the peripheral retina in this patient population. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  19. Clinical, developmental and molecular update on Cornelia de Lange syndrome and the cohesin complex: abstracts from the 2014 Scientific and Educational Symposium.

    PubMed

    Kline, Antonie D; Calof, Anne L; Lander, Arthur D; Gerton, Jennifer L; Krantz, Ian D; Dorsett, Dale; Deardorff, Matthew A; Blagowidow, Natalie; Yokomori, Kyoko; Shirahige, Katsuhiko; Santos, Rosaysela; Woodman, Julie; Megee, Paul C; O'Connor, Julia T; Egense, Alena; Noon, Sarah; Belote, Maurice; Goodban, Marjorie T; Hansen, Blake D; Timmons, Jenni Glad; Musio, Antonio; Ishman, Stacey L; Bryan, Yvon; Wu, Yaning; Bettini, Laura R; Mehta, Devanshi; Zakari, Musinu; Mills, Jason A; Srivastava, Siddharth; Haaland, Richard E

    2015-06-01

    Cornelia de Lange Syndrome (CdLS) is the most common example of disorders of the cohesin complex, or cohesinopathies. There are a myriad of clinical issues facing individuals with CdLS, particularly in the neurodevelopmental system, which also have implications for the parents and caretakers, involved professionals, therapists, and schools. Basic research in developmental and cell biology on cohesin is showing significant progress, with improved understanding of the mechanisms and the possibility of potential therapeutics. The following abstracts are presentations from the 6th Cornelia de Lange Syndrome Scientific and Educational Symposium, which took place on June 25-26, 2014, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting in Costa Mesa, CA. The Research Committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board. In addition to the scientific and clinical discussions, there were educationally focused talks related to practical aspects of behavior and development. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. © 2015 Wiley Periodicals, Inc.

  20. Patients carrying 9q31.1-q32 deletion share common features with Cornelia de Lange Syndrome.

    PubMed

    Cao, Ruixue; Pu, Tian; Fang, Shaohai; Long, Fei; Xie, Jing; Xu, Yuejuan; Chen, Sun; Sun, Kun; Xu, Rang

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare but severe clinically heterogeneous developmental disorder characterized by facial dysmorphia, growth and cognitive retardation, and abnormalities of limb development. To determine the pathogenesis of a patient with CdLS. We studied a patient with CdLS by whole exome sequencing, karyotyping and Agilent CGH Array. The results were confirmed by quantitative real-time PCR analysis of the patient and her parents. Further comparison of our patient and cases with partially overlapping deletions retrieved from the literature and databases was undertaken. Whole exome sequencing had excluded the mutation of cohesion genes such as NIPBL,SMC1A and SMC3. The result of karyotyping showed a deletion of chromosome 9q31.1-q32 and the result of Agilent CGH Array further displayed a 12.01-Mb region of deletion at chromosome bands 9q31.1-q32. Reported cases with the deletion of 9q31.1-q32 share similar features with our CdLS patient. One of the genes in the deleted region, SMC2, belongs to the Structural Maintenance of Chromosomes (SMC) family and regulates gene expression and DNA repair. Patients carrying the deletion of 9q31.1-q32 showed similar phenotypes with CdLS. © 2015 S. Karger AG, Basel.

  1. De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes.

    PubMed

    Gil-Rodríguez, María Concepción; Deardorff, Matthew A; Ansari, Morad; Tan, Christopher A; Parenti, Ilaria; Baquero-Montoya, Carolina; Ousager, Lilian B; Puisac, Beatriz; Hernández-Marcos, María; Teresa-Rodrigo, María Esperanza; Marcos-Alcalde, Iñigo; Wesselink, Jan-Jaap; Lusa-Bernal, Silvia; Bijlsma, Emilia K; Braunholz, Diana; Bueno-Martinez, Inés; Clark, Dinah; Cooper, Nicola S; Curry, Cynthia J; Fisher, Richard; Fryer, Alan; Ganesh, Jaya; Gervasini, Cristina; Gillessen-Kaesbach, Gabriele; Guo, Yiran; Hakonarson, Hakon; Hopkin, Robert J; Kaur, Maninder; Keating, Brendan J; Kibaek, María; Kinning, Esther; Kleefstra, Tjitske; Kline, Antonie D; Kuchinskaya, Ekaterina; Larizza, Lidia; Li, Yun R; Liu, Xuanzhu; Mariani, Milena; Picker, Jonathan D; Pié, Ángeles; Pozojevic, Jelena; Queralt, Ethel; Richer, Julie; Roeder, Elizabeth; Sinha, Anubha; Scott, Richard H; So, Joyce; Wusik, Katherine A; Wilson, Louise; Zhang, Jianguo; Gómez-Puertas, Paulino; Casale, César H; Ström, Lena; Selicorni, Angelo; Ramos, Feliciano J; Jackson, Laird G; Krantz, Ian D; Das, Soma; Hennekam, Raoul C M; Kaiser, Frank J; FitzPatrick, David R; Pié, Juan

    2015-04-01

    Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for ∼ 1%-2% of CdLS-like phenotypes. © 2015 WILEY PERIODICALS, INC.

  2. Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome.

    PubMed

    Teresa-Rodrigo, María E; Eckhold, Juliane; Puisac, Beatriz; Pozojevic, Jelena; Parenti, Ilaria; Baquero-Montoya, Carolina; Gil-Rodríguez, María C; Braunholz, Diana; Dalski, Andreas; Hernández-Marcos, María; Ayerza, Ariadna; Bernal, María L; Ramos, Feliciano J; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Pié, Juan; Kaiser, Frank J

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)_(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease.

  3. Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with Cornelia de Lange syndrome.

    PubMed

    Teresa-Rodrigo, María E; Eckhold, Juliane; Puisac, Beatriz; Dalski, Andreas; Gil-Rodríguez, María C; Braunholz, Diana; Baquero, Carolina; Hernández-Marcos, María; de Karam, Juan C; Ciero, Milagros; Santos-Simarro, Fernando; Lapunzina, Pablo; Wierzba, Jolanta; Casale, César H; Ramos, Feliciano J; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J; Pié, Juan

    2014-06-10

    Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B'. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame.

  4. Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-) mouse, a model of Cornelia de Lange Syndrome.

    PubMed

    Kawauchi, Shimako; Calof, Anne L; Santos, Rosaysela; Lopez-Burks, Martha E; Young, Clint M; Hoang, Michelle P; Chua, Abigail; Lao, Taotao; Lechner, Mark S; Daniel, Jeremy A; Nussenzweig, Andre; Kitzes, Leonard; Yokomori, Kyoko; Hallgrimsson, Benedikt; Lander, Arthur D

    2009-09-01

    Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75-80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only approximately 30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/- mice and in individuals with CdLS.

  5. Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome

    PubMed Central

    Teresa-Rodrigo, María E.; Eckhold, Juliane; Puisac, Beatriz; Pozojevic, Jelena; Parenti, Ilaria; Baquero-Montoya, Carolina; Gil-Rodríguez, María C.; Braunholz, Diana; Dalski, Andreas; Hernández-Marcos, María; Ayerza, Ariadna; Bernal, María L.; Ramos, Feliciano J.; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Pié, Juan; Kaiser, Frank J.

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)_(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease. PMID:26925417

  6. Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome

    PubMed Central

    Teresa-Rodrigo, María E.; Eckhold, Juliane; Puisac, Beatriz; Dalski, Andreas; Gil-Rodríguez, María C.; Braunholz, Diana; Baquero, Carolina; Hernández-Marcos, María; de Karam, Juan C.; Ciero, Milagros; Santos-Simarro, Fernando; Lapunzina, Pablo; Wierzba, Jolanta; Casale, César H.; Ramos, Feliciano J.; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J.; Pié, Juan

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame. PMID:24918291

  7. l-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome

    PubMed Central

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E.; Gerton, Jennifer L.

    2015-01-01

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. PMID:25378554

  8. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

    PubMed

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

    2015-03-15

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

  9. Benefits and limitations of a multidisciplinary approach to individualized management of Cornelia de Lange syndrome and related diagnoses.

    PubMed

    January, Kathleen; Conway, Laura J; Deardorff, Matthew; Harrington, Ann; Krantz, Ian D; Loomes, Kathleen; Pipan, Mary; Noon, Sarah E

    2016-06-01

    Given the clinical complexities of Cornelia de Lange Syndrome (CdLS), the Center for CdLS and Related Diagnoses at The Children's Hospital of Philadelphia (CHOP) and The Multidisciplinary Clinic for Adolescents and Adults at Greater Baltimore Medical Center (GBMC) were established to develop a comprehensive approach to clinical management and research issues relevant to CdLS. Little work has been done to evaluate the general utility of a multispecialty approach to patient care. Previous research demonstrates several advantages and disadvantages of multispecialty care. This research aims to better understand the benefits and limitations of a multidisciplinary clinic setting for individuals with CdLS and related diagnoses. Parents of children with CdLS and related diagnoses who have visited a multidisciplinary clinic (N = 52) and who have not visited a multidisciplinary clinic (N = 69) were surveyed to investigate their attitudes. About 90.0% of multispecialty clinic attendees indicated a preference for multidisciplinary care. However, some respondents cited a need for additional clinic services including more opportunity to meet with other specialists (N = 20), such as behavioral health, and increased information about research studies (N = 15). Travel distance and expenses often prevented families' multidisciplinary clinic attendance (N = 41 and N = 35, respectively). Despite identified limitations, these findings contribute to the evidence demonstrating the utility of a multispecialty approach to patient care. This approach ultimately has the potential to not just improve healthcare for individuals with CdLS but for those with medically complex diagnoses in general. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Attitudes about the use of internet support groups and the impact among parents of children with Cornelia de Lange syndrome.

    PubMed

    Cacioppo, Cara N; Conway, Laura J; Mehta, Devanshi; Krantz, Ian D; Noon, Sarah E

    2016-06-01

    There is an abundance of information in the literature on patient experiences with Internet support groups (ISGs). However, studies exploring these experiences in a rare disease population are scarce, even though these families are often at a disadvantage for resources, reliable information, and support. The aim of the current study was to explore the experiences with ISGs for parents of children with Cornelia de Lange syndrome (CdLS), a rare genetic diagnosis, in order to better understand the impact on emotional support and their child's medical care. Focus groups were conducted to inform the design of a large-scale internet survey. The survey asked parents closed- and open-ended questions regarding experiences with ISGs, with a focus on the psychosocial, medical, and logistical aspects. The survey found that 141/170 (82.6%) respondents have visited an Internet-based support group to find support or information about their child's CdLS diagnosis. The majority of respondents (71.7%) reported that ISGs have been helpful in finding emotional support, with the most common areas impacted as a result of ISG participation being behavior toward their children and family dynamic. Regarding medical care, most respondents (63.9%) reported that ISGs have been helpful in finding medical information and support, with the most commonly impacted areas of their child's care including day-to-day management, diet, therapy interventions, and healthcare providers. These findings provide a greater understanding of the role of Internet networking in healthcare and may inform future approaches to medical care and psychosocial support for rare, complex genetic diagnoses. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Using Mouse and Zebrafish Models to Understand the Etiology of Developmental Defects in Cornelia de Lange Syndrome

    PubMed Central

    KAWAUCHI, SHIMAKO; SANTOS, ROSAYSELA; MUTO, AKIHIKO; LOPEZ-BURKS, MARTHA E.; SCHILLING, THOMAS F.; LANDER, ARTHUR D.; CALOF, ANNE L.

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem birth defects disorder that affects every tissue and organ system in the body. Understanding the factors that contribute to the origins, prevalence, and severity of these developmental defects provides the most direct approach for developing screens and potential treatments for individuals with CdLS. Since the majority of cases of CdLS are caused by haploinsufficiency for NIPBL (Nipped-B-like, which encodes a cohesin-associated protein), we have developed mouse and zebrafish models of CdLS by using molecular genetic tools to create Nipbl-deficient mice and zebrafish (Nipbl+/− mice, zebrafish nipbl morphants). Studies of these vertebrate animal models have yielded novel insights into the developmental etiology and genes/gene pathways that contribute to CdLS-associated birth defects, particularly defects of the gut, heart, craniofacial structures, nervous system, and limbs. Studies of these mouse and zebrafish CdLS models have helped clarify how deficiency for NIPBL, a protein that associates with cohesin and other transcriptional regulators in the nucleus, affects processes important to the emergence of the structural and physiological birth defects observed in CdLS: NIPBL exerts chromosome position-specific effects on gene expression; it influences long-range interactions between different regulatory elements of genes; and it regulates combinatorial and synergistic actions of genes in developing tissues. Our current understanding is that CdLS should be considered as not only a cohesinopathy, but also a “transcriptomopathy,” that is, a disease whose underlying etiology is the global dysregulation of gene expression throughout the organism. PMID:27120001

  12. Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano–Ward syndrome

    PubMed Central

    Mousavi Nik, Atefeh; Gharaie, Somayeh; Jeong Kim, Hyo

    2015-01-01

    As a result of cell-specific functions of voltage-activated K+ channels, such as Kv7.1, mutations in this channel produce profound cardiac and auditory defects. At the same time, the massive diversity of K+ channels allows for compensatory substitution of mutant channels by other functional channels of their type to minimize defective phenotypes. Kv7.1 represents a clear example of such functional dichotomy. While several point mutations in the channel result in a cardio-auditory syndrome called Jervell and Lange-Nielsen syndrome (JLNS), about 100-fold mutations result in long QT syndrome (LQTS) denoted as Romano–Ward syndrome (RWS), which has an intact auditory phenotype. To determine whether the cellular mechanisms for the diverse phenotypic outcome of Kv7.1 mutations, are dependent on the tissue-specific function of the channel and/or specialized functions of the channel, we made series of point mutations in hKv7.1 ascribed to JLNS and RWS. For JLNS mutations, all except W248F yielded non-functional channels when expressed alone. Although W248F at the end of the S4 domain yielded a functional current, it underwent marked inactivation at positive voltages, rendering the channel non-functional. We demonstrate that by definition, none of the JLNS mutants operated in a dominant negative (DN) fashion. Instead, the JLNS mutants have impaired membrane trafficking, trapped in the endoplasmic reticulum (ER) and Cis-Golgi. The RWS mutants exhibited varied functional phenotypes. However, they can be summed up as exhibiting DN effects. Phenotypic differences between JLNS and RWS may stem from tissue-specific functional requirements of cardiac vs. inner ear non-sensory cells. PMID:25705178

  13. Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016.

    PubMed

    Kline, Antonie D; Krantz, Ian D; Deardorff, Matthew A; Shirahige, Katsuhiko; Dorsett, Dale; Gerton, Jennifer L; Wu, Meng; Mehta, Devanshi; Mills, Jason A; Carrico, Cheri S; Noon, Sarah; Herrera, Pamela S; Horsfield, Julia A; Bettale, Chiara; Morgan, Jeremy; Huisman, Sylvia A; Moss, Jo; McCleery, Joseph; Grados, Marco; Hansen, Blake D; Srivastava, Siddharth; Taylor-Snell, Emily; Kerr, Lynne M; Katz, Olivia; Calof, Anne L; Musio, Antonio; Egense, Alena; Haaland, Richard E

    2017-05-01

    Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22-23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. © 2017 Wiley Periodicals, Inc.

  14. Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome.

    PubMed

    Remeseiro, Silvia; Cuadrado, Ana; Kawauchi, Shimako; Calof, Anne L; Lander, Arthur D; Losada, Ana

    2013-12-01

    Cornelia de Lange Syndrome (CdLS) is a genetic disorder linked to mutations in cohesin and its regulators. To date, it is unclear which function of cohesin is more relevant to the pathology of the syndrome. A mouse heterozygous for the gene encoding the cohesin loader Nipbl recapitulates many features of CdLS. We have carefully examined Nipbl deficient cells and here report that they have robust cohesion all along the chromosome. DNA replication, DNA repair and chromosome segregation are carried out efficiently in these cells. While bulk cohesin loading is unperturbed, binding to certain promoters such as the Protocadherin genes in brain is notably affected and alters gene expression. These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes. © 2013 Elsevier B.V. All rights reserved.

  15. i-gel: a new supraglottic device for effective resuscitation of a very low birthweight infant with Cornelia de Lange syndrome

    PubMed Central

    Galderisi, Alfonso; De Bernardo, Giuseppe; Lorenzon, Eleonora; Trevisanuto, Daniele

    2015-01-01

    Laryngeal Mask Airway (LMA) has been indicated as an effective device for airway management when face-mask ventilation and intubation have both failed in infants weighing >2000 g or delivered ≥34 weeks of gestation. All previous studies used a classic LMA. The current report describes the first case of a very low birthweight infant (1470 g, <3rd centile; 36+3gestational weeks) with micrognathia and palate cleft with Cornelia De Lange syndrome, resuscitated at birth with a new supraglottic airway device, i-gel size-1, positioned by a trainee paediatrician at first attempt. The procedure allowed reaching prompt effective ventilation and oxygenation of the patient, who was stabilised and intubated through i-gel. PMID:25809435

  16. Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia De Lange syndrome.

    PubMed

    Esposito, Susanna; Selicorni, Angelo; Daleno, Cristina; Valzano, Antonia; Cerutti, Marta; Galeone, Carlotta; Consolo, Silvia; Menni, Francesca; Principi, Nicola

    2011-06-01

    In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

  17. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome

    PubMed Central

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-01-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1−/− mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0–P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner’s membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1−/− mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. PMID:26084842

  18. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

    PubMed

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-08-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss.

  19. Mutations in Cohesin Complex Members SMC3 and SMC1A Cause a Mild Variant of Cornelia de Lange Syndrome with Predominant Mental Retardation

    PubMed Central

    Deardorff, Matthew A.; Kaur, Maninder; Yaeger, Dinah; Rampuria, Abhinav; Korolev, Sergey; Pie, Juan; Gil-Rodríguez, Concepcion; Arnedo, María; Loeys, Bart; Kline, Antonie D.; Wilson, Meredith; Lillquist, Kaj; Siu, Victoria; Ramos, Feliciano J.; Musio, Antonio; Jackson, Laird S.; Dorsett, Dale; Krantz, Ian D.

    2007-01-01

    Mutations in the cohesin regulators NIPBL and ESCO2 are causative of the Cornelia de Lange syndrome (CdLS) and Roberts or SC phocomelia syndrome, respectively. Recently, mutations in the cohesin complex structural component SMC1A have been identified in two probands with features of CdLS. Here, we report the identification of a mutation in the gene encoding the complementary subunit of the cohesin heterodimer, SMC3, and 14 additional SMC1A mutations. All mutations are predicted to retain an open reading frame, and no truncating mutations were identified. Structural analysis of the mutant SMC3 and SMC1A proteins indicate that all are likely to produce functional cohesin complexes, but we posit that they may alter their chromosome binding dynamics. Our data indicate that SMC3 and SMC1A mutations (1) contribute to ∼5% of cases of CdLS, (2) result in a consistently mild phenotype with absence of major structural anomalies typically associated with CdLS, and (3) in some instances, result in a phenotype that approaches that of apparently nonsyndromic mental retardation. PMID:17273969

  20. Exclusion of Linkage to the CDL1 Gene Region on Chromosome 3q26.3 in Some Familial Cases of Cornelia de Lange Syndrome

    PubMed Central

    Krantz, Ian D.; Tonkin, Emma; Smith, Melanie; Devoto, Marcella; Bottani, Armand; Simpson, Claire; Hofreiter, Mary; Abraham, Vinod; Jukofsky, Lori; Conti, Brian P.; Strachan, Tom; Jackson, Laird

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a complex developmental disorder consisting of characteristic facial features, limb abnormalities, hirsutism, ophthalmologic involvement, gastroesophageal dysfunction, hearing loss, as well as growth and neuro-developmental retardation. Most cases of CdLS appear to be sporadic. Familial cases are rare and indicate autosomal dominant inheritance. Several individuals with CdLS have been reported with chromosomal abnormalities, suggesting candidate genomic regions within which the causative gene(s) may lie. A CdLS gene location (CDL1) has been assigned to 3q26.3 based on phenotypic overlap with the duplication 3q syndrome (critical region 3q26.2-q27) and the report of a CdLS individual with a balanced de novo t(3;17)(q26.3;q23.1). It has been postulated that a gene within the dup3q critical region results in the CdLS when deleted or mutated. We have performed a linkage analysis to the minimal critical region for the dup3q syndrome (that encompasses the translocation breakpoint) on chromosome 3q in 10 rare familial cases of CdLS. Nineteen markers spanning a region of approximately 40 Mb (37 cM) were used. Results of a multipoint linkage analysis demonstrated total lod-scores that were negative across the chromosome 3q26-q27 region. In 4/10 families, lod-scores were less than −2 in the 2 cM region encompassing the translocation, while in the remaining 6/10 families, lod-scores could not exclude linkage to this region. These studies indicate that in some multicase families, the disease gene does not map to the CDL1 region at 3q26.3. PMID:11391654

  1. Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.

    PubMed

    Woods, Susan A; Robinson, Haynes B; Kohler, Lisa J; Agamanolis, Dimitris; Sterbenz, George; Khalifa, Mohamed

    2014-01-01

    Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions. In addition, although EP300 and CREBBP encode homologous proteins and perform similar functions, only eight EP300 positive RTS patients have been reported, suggesting that patients with EP300 mutations might be escaping clinical recognition. We report on a child with multiple congenital abnormalities and intellectual disability whose facial features and complex phenotype resemble CdLS. However, no mutations in CdLS-related genes were identified. Rather, a novel EP300 mutation was found on whole exome sequencing. Possible links between EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8 are involved in the regulation of TP53 transcriptional activity. In addition, p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3, have been found at enhancer regions in different cell types. It is therefore possible that EP300 and CdLS-related genes are involved in additional shared pathways, producing overlapping phenotypes. As whole exome sequencing becomes more widely utilized, the diverse phenotypes associated with EP300 mutations should be better understood. In the meantime, testing for EP300 mutations in those with features of CdLS may be warranted. © 2013 Wiley Periodicals, Inc.

  2. Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing

    PubMed Central

    Jang, Mi-Ae; Lee, Chang-Woo

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS. PMID:26354354

  3. Deletion of 11q12.3-11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome.

    PubMed

    Boyle, Martine Isabel; Jespersgaard, Cathrine; Nazaryan, Lusine; Ravn, Kirstine; Brøndum-Nielsen, Karen; Bisgaard, Anne-Marie; Tümer, Zeynep

    2015-11-01

    Deletions within 11q12.3-11q13.1 are very rare and to date only two cases have been described in the literature. In this study we describe a 23-year-old male patient with intellectual disability, behavioral problems, dysmorphic features, dysphagia, gastroesophageal reflux and skeletal abnormalities. Cornelia de Lange syndrome (CdLS, OMIM #122470; #300590; #610759; #300882; #614701) was suggested as a differential diagnosis in childhood although he lacked some of the features typical for this disorder. He does not have a mutation in any of the five known CdLS genes (NIPBL, SMC1A, SMC3, HDAC8, RAD21), but a 1.6Mb deletion at chromosome region 11q12.3-11q13.1 was detected by chromosome microarray. The deletion contains several genes including PPP2R5B, which has been associated with intellectual disability and overgrowth; NRXN2, which has been associated with intellectual disability and autism spectrum disorder; and CDCA5, which is part of the cohesin pathway, as are all the five known CdLS genes. It is therefore possible that deletion of CDCA5 may account for some of the CdLS like features of the present case. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Two novel RAD21 mutations in patients with mild Cornelia de Lange syndrome-like presentation and report of the first familial case.

    PubMed

    Minor, Agata; Shinawi, Marwan; Hogue, Jacob S; Vineyard, Marisa; Hamlin, Damara R; Tan, Christopher; Donato, Kirsten; Wysinger, Latrice; Botes, Shaun; Das, Soma; Del Gaudio, Daniela

    2014-03-10

    Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by limb reduction defects, characteristic facial features and impaired cognitive development. Mutations in the NIPBL gene predominate; however, mutations in other cohesin complex genes have also been implicated, particularly in atypical and mild CdLS cases. Missense mutations and whole gene deletions in RAD21 have been identified in children with growth retardation, minor skeletal anomalies and facial features that overlap findings in individuals with CdLS. We report the first intragenic deletion and frameshift mutations identified in RAD21 in two patients presenting with atypical CdLS. One patient had an in-frame deletion of exon 13, while the second patient had a c.592_593dup frameshift mutation. The first patient presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features while, the second patient presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies, with the first patient being milder than the second. The in-frame deletion mutation was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. This study expands the spectrum of RAD21 mutations and emphasizes the clinical utility of performing RAD21 mutation analysis in patients presenting with atypical forms of CdLS. Moreover, the variability of clinical presentation within families and low penetrance of mutations as well as the significance of performing molecular genetic testing in mildly affected patients are discussed. Published by Elsevier B.V.

  5. Novel pathogenic variant (c.3178G>A) in the SMC1A gene in a family with Cornelia de Lange syndrome identified by exome sequencing.

    PubMed

    Jang, Mi Ae; Lee, Chang Woo; Kim, Jin Kyung; Ki, Chang Seok

    2015-11-01

    Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS.

  6. Mutations and Variants in the Cohesion factor genes NIPBL, SMC1A and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange Syndrome

    PubMed Central

    Pié, Juan; Gil-Rodríguez, María Concepción; Ciero, Milagros; López-Viñas, Eduardo; Ribate, María Pilar; Arnedo, María; Deardorff, Matthew A.; Puisac, Beatriz; Legarreta, Jesús; de Karam, Juan Carlos; Rubio, Encarnación; Bueno, Inés; Baldellou, Antonio; Calvo, Mª Teresa; Casals, Nuria; Olivares, José Luis; Losada, Ana; Hegardt, Fausto G.; Krantz, Ian D.; Gómez-Puertas, Paulino; Ramos, Feliciano J.

    2010-01-01

    Cornelia de Lange Syndrome (CdLS) and manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes (NIPBL, SMC1A and SMC3) of the Cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex. PMID:20358602

  7. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism

    PubMed Central

    Ansari, Morad; Poke, Gemma; Ferry, Quentin; Williamson, Kathleen; Aldridge, Roland; Meynert, Alison M; Bengani, Hemant; Chan, Cheng Yee; Kayserili, Hülya; Avci, Şahin; Hennekam, Raoul C M; Lampe, Anne K; Redeker, Egbert; Homfray, Tessa; Ross, Alison; Falkenberg Smeland, Marie; Mansour, Sahar; Parker, Michael J; Cook, Jacqueline A; Splitt, Miranda; Fisher, Richard B; Fryer, Alan; Magee, Alex C; Wilkie, Andrew; Barnicoat, Angela; Brady, Angela F; Cooper, Nicola S; Mercer, Catherine; Deshpande, Charu; Bennett, Christopher P; Pilz, Daniela T; Ruddy, Deborah; Cilliers, Deirdre; Johnson, Diana S; Josifova, Dragana; Rosser, Elisabeth; Thompson, Elizabeth M; Wakeling, Emma; Kinning, Esther; Stewart, Fiona; Flinter, Frances; Girisha, Katta M; Cox, Helen; Firth, Helen V; Kingston, Helen; Wee, Jamie S; Hurst, Jane A; Clayton-Smith, Jill; Tolmie, John; Vogt, Julie; Tatton–Brown, Katrina; Chandler, Kate; Prescott, Katrina; Wilson, Louise; Behnam, Mahdiyeh; McEntagart, Meriel; Davidson, Rosemarie; Lynch, Sally-Ann; Sisodiya, Sanjay; Mehta, Sarju G; McKee, Shane A; Mohammed, Shehla; Holden, Simon; Park, Soo-Mi; Holder, Susan E; Harrison, Victoria; McConnell, Vivienne; Lam, Wayne K; Green, Andrew J; Donnai, Dian; Bitner-Glindzicz, Maria; Donnelly, Deirdre E; Nellåker, Christoffer; Taylor, Martin S; FitzPatrick, David R

    2014-01-01

    Background Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. Conclusions Future diagnostic testing in ‘mutation-negative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues. PMID:25125236

  8. Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: disease mechanisms and pharmacological rescue.

    PubMed

    Zhang, Miao; D'Aniello, Cristina; Verkerk, Arie O; Wrobel, Eva; Frank, Stefan; Ward-van Oostwaard, Dorien; Piccini, Ilaria; Freund, Christian; Rao, Jyoti; Seebohm, Guiscard; Atsma, Douwe E; Schulze-Bahr, Eric; Mummery, Christine L; Greber, Boris; Bellin, Milena

    2014-12-16

    Jervell and Lange-Nielsen syndrome (JLNS) is one of the most severe life-threatening cardiac arrhythmias. Patients display delayed cardiac repolarization, associated high risk of sudden death due to ventricular tachycardia, and congenital bilateral deafness. In contrast to the autosomal dominant forms of long QT syndrome, JLNS is a recessive trait, resulting from homozygous (or compound heterozygous) mutations in KCNQ1 or KCNE1. These genes encode the α and β subunits, respectively, of the ion channel conducting the slow component of the delayed rectifier K(+) current, IKs. We used complementary approaches, reprogramming patient cells and genetic engineering, to generate human induced pluripotent stem cell (hiPSC) models of JLNS, covering splice site (c.478-2A>T) and missense (c.1781G>A) mutations, the two major classes of JLNS-causing defects in KCNQ1. Electrophysiological comparison of hiPSC-derived cardiomyocytes (CMs) from homozygous JLNS, heterozygous, and wild-type lines recapitulated the typical and severe features of JLNS, including pronounced action and field potential prolongation and severe reduction or absence of IKs. We show that this phenotype had distinct underlying molecular mechanisms in the two sets of cell lines: the previously unidentified c.478-2A>T mutation was amorphic and gave rise to a strictly recessive phenotype in JLNS-CMs, whereas the missense c.1781G>A lesion caused a gene dosage-dependent channel reduction at the cell membrane. Moreover, adrenergic stimulation caused action potential prolongation specifically in JLNS-CMs. Furthermore, sensitivity to proarrhythmic drugs was strongly enhanced in JLNS-CMs but could be pharmacologically corrected. Our data provide mechanistic insight into distinct classes of JLNS-causing mutations and demonstrate the potential of hiPSC-CMs in drug evaluation.

  9. Are Angelman and Prader-Willi syndromes more similar than we thought? Food-related behavior problems in Angelman, Cornelia de Lange, fragile X, Prader-Willi and 1p36 deletion syndromes.

    PubMed

    Welham, Alice; Lau, Johnny; Moss, Joanna; Cullen, Jenny; Higgs, Suzanne; Warren, Gemma; Wilde, Lucy; Marr, Abby; Cook, Faye; Oliver, Chris

    2015-03-01

    Food-related behavior problems are well documented in Prader-Willi syndrome (PWS), with impaired satiety, preoccupation with food and negative food-related behaviors (such as taking and storing food) frequently reported as part of the behavioral phenotype of older children and adults. Food-related behavior problems in other genetic neurodevelopmental syndromes remain less well studied, including those seen in Angelman Syndrome (AS), the 'sister imprinted disorder' of PWS. Food-related behavior problems were assessed in 152 participants each with one of five genetic neurodevelopmental syndromes – PWS, AS, 1p36 deletion, Cornelia de Lange, and fragile X. Predictably, levels of food-related behavior problems reported in participants with PWS significantly exceeded those of at least one other groups in most areas (impaired satiety; preoccupation with food; taking and storing food; composite negative behavior). However, in some areas people with AS were reported to display food-related problems at least as severe as those with PWS, with the AS group reported to display significantly more food-related behavior problems than at least one comparison group on measures of taking and storing food, composite negative behaviors, impaired satiety and preoccupation with food. Over 50% of participants in the AS group scored above the median point of the distribution of PWS scores on a measure of taking and storing food. These findings indicate further investigation of eating problems in AS are warranted and have implications for current theoretical interpretations of the behavioral differences between AS and PWS.

  10. Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome.

    PubMed

    Wenger, Tara L; Chow, Penny; Randle, Stephanie C; Rosen, Anna; Birgfeld, Craig; Wrede, Joanna; Javid, Patrick; King, Darcy; Manh, Vivian; Hing, Anne V; Albers, Erin

    2017-02-01

    Relatively few patients with Cornelia de Lange syndrome (CdLS) due to SMC1A mutation have been reported, limiting understanding of the full extent of the phenotype. Compared to children with classic NIPBL-associated CdLS, patients with SMC1A-associated CdLS have a milder physical phenotype with prominent intellectual disability, high rate of cleft palate and absence of limb reductions. We present a patient with SMC1A-associated CdLS who had typical features including developmental delay, seizure disorder, feeding difficulties, hirsutism, and cleft palate. She also was found to have three novel features: (i) left ventricular non-compaction (LVNC) cardiomyopathy; (ii) microform cleft lip; and (iii) severe hyperopia and astigmatism. These features have implications regarding potential insight into the pathogenesis of the disorder, screening, and medical management. Hypertrophic cardiomyopathy has previously been reported in SMC1A-associated CdLS, but to our knowledge this is the first reported child with LVNC. Previous reports have included children with isolated clefts of the palate without involvement of the lip. When cleft palate alone is associated with a disorder, the underlying pathophysiology for clefting is sometimes secondary due to mechanical blocking of the fusion of the palatal shelves with the developing tongue. The presence of microform cleft lip in this patient suggests that the pathophysiology of clefting in SMC1A is primary rather than secondary. Few studies report ophthalmologic findings specific to SMC1A. Based on these findings, LVNC cardiomyopathy and cleft lip should be considered features of SMC1A-associated CdLS. All patients should receive echocardiogram and undergo thorough ophthalmologic evaluation as part of routine CdLS care. © 2016 Wiley Periodicals, Inc.

  11. Overall and allele-specific expression of the SMC1A gene in female Cornelia de Lange syndrome patients and healthy controls

    PubMed Central

    Parenti, Ilaria; Rovina, Davide; Masciadri, Maura; Cereda, Anna; Azzollini, Jacopo; Picinelli, Chiara; Limongelli, Giuseppe; Finelli, Palma; Selicorni, Angelo; Russo, Silvia; Gervasini, Cristina; Larizza, Lidia

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, limb anomalies, and growth and cognitive deficits. Mutations in genes encoding subunits (SMC1A, SMC3, RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex account for approximately 65% of clinically diagnosed CdLS cases. The SMC1A gene (Xp11.22), responsible for 5% of CdLS cases, partially escapes X chromosome inactivation in humans and the allele on the inactive X chromosome is variably expressed. In this study, we evaluated overall and allele-specific SMC1A expression. Real-time PCR analysis conducted on 17 controls showed that SMC1A expression in females is 50% higher than in males. Immunoblotting experiments confirmed a 44% higher protein level in healthy females than in males, and showed no significant differences in SMC1A protein levels between controls and patients. Pyrosequencing was used to assess the reciprocal level of allelic expression in six female carriers of different SMC1A mutations and 15 controls who were heterozygous at a polymorphic transcribed SMC1A locus. The two alleles were expressed at a 1:1 ratio in the control group and at a 2:1 ratio in favor of the wild type allele in the test group. Since a dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. An extension of this study to a larger cohort containing mild to borderline cases could enhance our understanding of the clinical spectrum of SMC1A-linked CdLS. PMID:24756084

  12. The effect of Nipped-B-like (Nipbl) haploinsufficiency on genome-wide cohesin binding and target gene expression: modeling Cornelia de Lange syndrome.

    PubMed

    Newkirk, Daniel A; Chen, Yen-Yun; Chien, Richard; Zeng, Weihua; Biesinger, Jacob; Flowers, Ebony; Kawauchi, Shimako; Santos, Rosaysela; Calof, Anne L; Lander, Arthur D; Xie, Xiaohui; Yokomori, Kyoko

    2017-01-01

    Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder frequently associated with heterozygous loss-of-function mutations of Nipped-B-like (NIPBL), the human homolog of Drosophila Nipped-B. NIPBL loads cohesin onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis but is also increasingly recognized as a regulator of gene expression. In CdLS patient cells and animal models, expression changes of multiple genes with little or no sister chromatid cohesion defect suggests that disruption of gene regulation underlies this disorder. However, the effect of NIPBL haploinsufficiency on cohesin binding, and how this relates to the clinical presentation of CdLS, has not been fully investigated. Nipbl haploinsufficiency causes CdLS-like phenotype in mice. We examined genome-wide cohesin binding and its relationship to gene expression using mouse embryonic fibroblasts (MEFs) from Nipbl+/- mice that recapitulate the CdLS phenotype. We found a global decrease in cohesin binding, including at CCCTC-binding factor (CTCF) binding sites and repeat regions. Cohesin-bound genes were found to be enriched for histone H3 lysine 4 trimethylation (H3K4me3) at their promoters; were disproportionately downregulated in Nipbl mutant MEFs; and displayed evidence of reduced promoter-enhancer interaction. The results suggest that gene activation is the primary cohesin function sensitive to Nipbl reduction. Over 50% of significantly dysregulated transcripts in mutant MEFs come from cohesin target genes, including genes involved in adipogenesis that have been implicated in contributing to the CdLS phenotype. Decreased cohesin binding at the gene regions is directly linked to disease-specific expression changes. Taken together, our Nipbl haploinsufficiency model allows us to analyze the dosage effect of cohesin loading on CdLS development.

  13. Overall and allele-specific expression of the SMC1A gene in female Cornelia de Lange syndrome patients and healthy controls.

    PubMed

    Parenti, Ilaria; Rovina, Davide; Masciadri, Maura; Cereda, Anna; Azzollini, Jacopo; Picinelli, Chiara; Limongelli, Giuseppe; Finelli, Palma; Selicorni, Angelo; Russo, Silvia; Gervasini, Cristina; Larizza, Lidia

    2014-07-01

    Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, limb anomalies, and growth and cognitive deficits. Mutations in genes encoding subunits (SMC1A, SMC3, RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex account for approximately 65% of clinically diagnosed CdLS cases. The SMC1A gene (Xp11.22), responsible for 5% of CdLS cases, partially escapes X chromosome inactivation in humans and the allele on the inactive X chromosome is variably expressed. In this study, we evaluated overall and allele-specific SMC1A expression. Real-time PCR analysis conducted on 17 controls showed that SMC1A expression in females is 50% higher than in males. Immunoblotting experiments confirmed a 44% higher protein level in healthy females than in males, and showed no significant differences in SMC1A protein levels between controls and patients. Pyrosequencing was used to assess the reciprocal level of allelic expression in six female carriers of different SMC1A mutations and 15 controls who were heterozygous at a polymorphic transcribed SMC1A locus. The two alleles were expressed at a 1:1 ratio in the control group and at a 2:1 ratio in favor of the wild type allele in the test group. Since a dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. An extension of this study to a larger cohort containing mild to borderline cases could enhance our understanding of the clinical spectrum of SMC1A-linked CdLS.

  14. Causes of Death and Autopsy Findings in a Large Study Cohort of Individuals with Cornelia de Lange Syndrome and Review of the Literature

    PubMed Central

    Schrier, Samantha A.; Sherer, Ilana; Deardorff, Matthew A.; Clark, Dinah; Audette, Lynn; Gillis, Lynette; Kline, Antonie D.; Ernst, Linda; Loomes, Kathy; Krantz, Ian D.; Jackson, Laird G.

    2011-01-01

    To identify causes of death (COD) in propositi with Cornelia de Lange syndrome (CdLS) at various ages, and to develop guidelines to improve management and avoid morbidity and mortality, we retrospectively reviewed a total of 426 propositi with confirmed clinical diagnoses of CdLS in our database who died in a 41-year period between 1966–2007. Of these, 295 had an identifiable COD reported to us. Clinical, laboratory and complete autopsy data were completed on 41, of which 38 were obtainable, an additional 19 had autopsies that only documented the COD, and 45 propositi had surgical, imaging, or terminal event clinical documentation of their COD. Proband ages ranged from fetuses (21 to 40 weeks gestation) to 61 years. A literature review was undertaken to identify all reported causes of death in CdLS individuals. In our cohort of 295 propositi with a known COD, respiratory causes including aspiration/reflux and pneumonias were the most common primary causes (31%), followed by gastrointestinal disease, including obstruction/volvulus (19%). Congenital anomalies accounted for 15% of deaths and included congenital diaphragmatic hernia and congenital heart defects. Acquired cardiac disease accounted for 3% of deaths. Neurological causes and accidents each accounted for 8%, sepsis for 4%, cancer for 2%, renal disease for 1.7%, and other causes, 9% of deaths. We also present 21 representative clinical cases for illustration. This comprehensive review has identified important etiologies contributing to the morbidity and mortality in this population that will provide for an improved understanding of clinical complications, and management for children and adults with CdLS. PMID:22069164

  15. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance

    PubMed Central

    Kaiser, Frank J.; Ansari, Morad; Braunholz, Diana; Concepción Gil-Rodríguez, María; Decroos, Christophe; Wilde, Jonathan J.; Fincher, Christopher T.; Kaur, Maninder; Bando, Masashige; Amor, David J.; Atwal, Paldeep S.; Bahlo, Melanie; Bowman, Christine M.; Bradley, Jacquelyn J.; Brunner, Han G.; Clark, Dinah; Del Campo, Miguel; Di Donato, Nataliya; Diakumis, Peter; Dubbs, Holly; Dyment, David A.; Eckhold, Juliane; Ernst, Sarah; Ferreira, Jose C.; Francey, Lauren J.; Gehlken, Ulrike; Guillén-Navarro, Encarna; Gyftodimou, Yolanda; Hall, Bryan D.; Hennekam, Raoul; Hudgins, Louanne; Hullings, Melanie; Hunter, Jennifer M.; Yntema, Helger; Innes, A. Micheil; Kline, Antonie D.; Krumina, Zita; Lee, Hane; Leppig, Kathleen; Lynch, Sally Ann; Mallozzi, Mark B.; Mannini, Linda; Mckee, Shane; Mehta, Sarju G.; Micule, Ieva; Mohammed, Shehla; Moran, Ellen; Mortier, Geert R.; Moser, Joe-Ann S.; Noon, Sarah E.; Nozaki, Naohito; Nunes, Luis; Pappas, John G.; Penney, Lynette S.; Pérez-Aytés, Antonio; Petersen, Michael B.; Puisac, Beatriz; Revencu, Nicole; Roeder, Elizabeth; Saitta, Sulagna; Scheuerle, Angela E.; Schindeler, Karen L.; Siu, Victoria M.; Stark, Zornitza; Strom, Samuel P.; Thiese, Heidi; Vater, Inga; Willems, Patrick; Williamson, Kathleen; Wilson, Louise C.; Hakonarson, Hakon; Quintero-Rivera, Fabiola; Wierzba, Jolanta; Musio, Antonio; Gillessen-Kaesbach, Gabriele; Ramos, Feliciano J.; Jackson, Laird G.; Shirahige, Katsuhiko; Pié, Juan; Christianson, David W.; Krantz, Ian D.; Fitzpatrick, David R.; Deardorff, Matthew A.

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS. PMID:24403048

  16. "Migrant Mother" by Dorothea Lange.

    ERIC Educational Resources Information Center

    Henry, Carole

    1995-01-01

    Maintains that the photograph, "Migrant Mother," is recognized throughout the world. Provides a three-part instructional unit on Dorothea Lange and social issues related to migrant workers. Includes four photographs by Lange, including the most well-known, "Migrant Mother 5." (CFR)

  17. Contrasting age related changes in autism spectrum disorder phenomenology in Cornelia de Lange, Fragile X, and Cri du Chat syndromes: Results from a 2.5 year follow-up.

    PubMed

    Cochran, Lisa; Moss, Joanna; Nelson, Lisa; Oliver, Chris

    2015-06-01

    Little is known about the way in which the characteristics of autism spectrum disorder (ASD) develop and manifest across the age span in individuals with genetic syndromes. In this study we present findings from a two and a half year follow-up of the characteristics associated with ASD in three syndromes: Cornelia de Lange (CdLS), Fragile X (FXS), and Cri du Chat (CdCS). Parents and carers of 251 individuals (CdLS=67, CdCS=42, and FXS=142) completed the Social Communication Questionnaire (SCQ) at Time 1 (T1) and again two and a half years later (T2). The FXS and CdLS groups were more likely to meet the cut-offs for both autism and ASD and show greater severity of ASD related behaviors, at both T1 and T2, compared to the CdCS group. Older individuals (>15yrs) with CdLS were more likely to meet the cut off for ASD than younger individuals (≤15 yrs) with the syndrome and more likely to show greater severity of social impairments. In FXS repetitive behaviors were found to become less prominent with age and in CdCS social impairments were reported to be more severe with age. There were no significant changes between T1 and T2 in the severity of ASD characteristics in the CdCS and CdLS groups. The FXS group showed significantly fewer repetitive behaviors and less severe impairments in social interaction over this time frame. The findings suggest that while there may be similarities in overall severity and presentation of ASD characteristics in CdLS and FXS, these characteristics have divergent patterns of development within these groups. © 2015 Wiley Periodicals, Inc.

  18. mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome.

    PubMed

    Puisac, Beatriz; Teresa-Rodrigo, María-Esperanza; Hernández-Marcos, María; Baquero-Montoya, Carolina; Gil-Rodríguez, María-Concepción; Visnes, Torkild; Bot, Christopher; Gómez-Puertas, Paulino; Kaiser, Frank J; Ramos, Feliciano J; Ström, Lena; Pié, Juan

    2017-02-23

    Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the NIPBL gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction). Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of NIPBL (c.8387A > G; P.Tyr2796Cys), showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.

  19. Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

    PubMed

    de León, Fernando Chico-Ponce; Gordillo-Domínguez, Luis F; González-Carranza, Vicente; Torres-García, Samuel; García-Delgado, Constanza; Sánchez-Boiso, Adriana; Arenas-Huertero, Francisco; Perezpeña-Diazconti, Mario; Eguía-Aguilar, Pilar; Baqueiro-Hernández, César; Buenrostro-Márquez, Guillermo; Martínez-Rodríguez, Sonia; Dhellemmes, Patrick; Castro-Sierra, Eduardo

    2015-01-01

    A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

  20. mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome

    PubMed Central

    Puisac, Beatriz; Teresa-Rodrigo, María-Esperanza; Hernández-Marcos, María; Baquero-Montoya, Carolina; Gil-Rodríguez, María-Concepción; Visnes, Torkild; Bot, Christopher; Gómez-Puertas, Paulino; Kaiser, Frank J.; Ramos, Feliciano J.; Ström, Lena; Pié, Juan

    2017-01-01

    Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the NIPBL gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction). Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of NIPBL (c.8387A > G; P.Tyr2796Cys), showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers. PMID:28241484

  1. Low-loss Lange coupler

    NASA Astrophysics Data System (ADS)

    Hobdell, J. L.; Biggin, J. W.; Band, K. S.

    1982-09-01

    The Lange coupler is used to make hybrid 3 dB couplers. In order to equalize the odd- and even-mode phase velocities, bond wires have to be used to join alternate lines of the coupler. In monolithic circuits the incorporation of bond wires is not possible, and techniques have been developed which involve the replacement of bond wires by air bridges. The present investigation is concerned with a comparison of the loss associated with air-bridge and wire-bonded couplers on alumina. It is found that the use of air-bridge straps on Lange couplers constructed on alumina gives couplers with a transmission loss which is lower than that observed in the case of an identical coupler using bond wires. The air-bridge technique also makes the mass production of circuits employing Lange couplers easier. The assembly step of bonding the coupler is eliminated at the expense of an extra fabrication step.

  2. Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3-q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1.

    PubMed

    Chen, Chih-Ping; Lin, Ming-Huei; Chen, Yi-Yung; Chern, Schu-Rern; Chen, Yen-Ni; Wu, Peih-Shan; Pan, Chen-Wen; Lee, Meng-Shan; Wang, Wayseen

    2015-10-01

    The aim of this research was to present prenatal diagnosis of Langer-Giedion syndrome (LGS/TRPS type II) and Cornelia de Lange syndrome-4 (CDLS4). A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis of amniocentesis revealed an interstitial deletion of chromosome 8q or del(8)(q23.3q24.13). Level II prenatal ultrasound examination revealed craniofacial dysmorphism. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism of LGS/TRPS type II and CDLS4. Whole-genome array comparative genomic hybridization (aCGH) on the DNA extracted from cultured amniocytes was performed. The analysis by aCGH revealed a result of arr 8q23.3q24.11 (116,087,006-118,969,399)×1, 8q24.13 (123,086,851-124,470,847)×1 (NCBI build 37) with a 2.88-Mb deletion of 8q23.3-q24.11 encompassing six OMIM genes, TRPS1, EIF3H, RAD21, SLC30A8, MED30, and EXT1, and a 1.383-Mb deletion of 8q24.13 encompassing four OMIM genes, ZHX2, DERL1, ZHX1, and ATAD2. In the present case, the conventional cytogenetic analysis of cultured amniocytes revealed del(8)(q23.3q24.13), whereas aCGH analysis of cultured amniocytes showed the deletions of 8q23.3-q24.11 and 8q24.13 with the presence of the segment 8q24.12. Therefore, aCGH provides the advantage of better understanding of the nature of interstitial deletion and genotype-phenotype correlation in this case. Copyright © 2015. Published by Elsevier B.V.

  3. Obituary: Andrew Lange (1957-2010)

    NASA Astrophysics Data System (ADS)

    Kamionkowski, Marc

    2011-12-01

    The worlds of physics and astrophysics were stunned to learn on 22 January 2010 that Andrew Lange, the Marvin L. Goldberger Professor of Physics at Caltech, had taken his own life the night before. He had succumbed to the severe depression that he had suffered from for many years, unbeknownst to even his closest colleagues. Lange will perhaps be best remembered as the co-leader of Boomerang, the balloon-borne experiment that provided the first high-angular-resolution map of the cosmic microwave background (CMB). And while this was certainly his most notable achievement, Andrew amassed a record of accomplishment as an instrumentalist, leader, mentor, and communicator that extended much further. Andrew was born in Urbana, Illinois on July 23, 1957, the son of an architect and a librarian, and raised primarily in Connecticut. His family and early friends remember him as a serious and extremely intelligent child and young man. Andrew Lange's lifelong interest in the CMB was nurtured as an undergraduate at Princeton University by David Wilkinson, and he recalled fondly a summer spent working with John Mather at Goddard Space Flight Center. Andrew Lange went to graduate school in physics at Berkeley where he worked in Paul Richards' group. Although his thesis project, the Berkeley-Nagoya rocket experiment, showed an anomalous sub-millimeter excess in the CMB spectrum that was shortly thereafter shown by a later flight of the same rocket and COBE-FIRAS to be incorrect, Lange's talents were recognized by the physics department at Berkeley who appointed him shortly after his PhD (1987) to their faculty. While on the Berkeley faculty, Andrew obtained early detections of the Sunyaev-Zeldovich effect, upper limits to small-angle CMB fluctuations, and important infrared constraints to the interstellar medium. He also led a pioneering instrument operating 300 mK detectors for a small infrared satellite experiment. This early work showed high ambition and daring, and it pioneered

  4. SuperMacLang: Development of an Authoring System.

    ERIC Educational Resources Information Center

    Frommer, Judith; Foelsche, Otmar K. E.

    1999-01-01

    Describes the development of "SuperMacLang, the 1990s version of the MacLang authoring system. An analysis of various features of the program explains the ways in which certain aspects of collaboration and funding affected developer and programming decisions. (Author/VWL)

  5. SuperMacLang: Development of an Authoring System.

    ERIC Educational Resources Information Center

    Frommer, Judith; Foelsche, Otmar K. E.

    1999-01-01

    Describes the development of "SuperMacLang, the 1990s version of the MacLang authoring system. An analysis of various features of the program explains the ways in which certain aspects of collaboration and funding affected developer and programming decisions. (Author/VWL)

  6. Chromosome Rearrangements in Cornelia de Lange Syndrome (CdLS): Report of a der(3)t(3;12)(p25.3;p13.3) in Two Half Sibs With Features of CdLS and Review of Reported CdLS Cases With Chromosome Rearrangements

    PubMed Central

    DeScipio, Cheryl; Kaur, Maninder; Yaeger, Dinah; Innis, Jeffrey W.; Spinner, Nancy B.; Jackson, Laird G.; Krantz, Ian D.

    2016-01-01

    Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited disorder characterized by multisystem involvement, cognitive delay, limb defects, and characteristic facial features. Recently, mutations in NIPBL have been found in ~50% of individuals with CdLS. Numerous chromosomal rearrangements have been reported in individuals with CdLS. These rearrangements may be causative of a CdLS phenotype, result in a phenocopy, or be unrelated to the observed phenotype. We describe two half siblings with a der(3)t(3;12)(p25.3;p13.3) chromosomal rearrangement, clinical features resembling CdLS, and phenotypic overlap with the del(3)(p25) phenotype. Region-specific BAC probes were used to fine-map the breakpoint region by fluorescence in situ hybridization (FISH). FISH analysis places the chromosome 3 breakpoint distal to RP11-115G3 on 3p25.3; the chromosome 12 breakpoint is distal to BAC RP11-88D16 on 12p13.3. A review of published cases of terminal 3p deletions and terminal 12p duplications indicates that the findings in these siblings are consistent with the del(3)(p25) phenotype. Given the phenotypic overlap with CdLS, we have reviewed the reported cases of chromosomal rearrangements involved in CdLS to better elucidate other potential loci that could harbor additional CdLS genes. Additionally, to identify chromosome rearrangements, genome-wide array comparative genomic hybridization (CGH) was performed on eight individuals with typical CdLS and without identifiable deletion or mutation of NIPBL. No pathologic rearrangements were identified. PMID:16075459

  7. 'On periodical depressions and their pathogenesis' by Carl Lange (1886).

    PubMed

    Schioldann, Johann

    2011-03-01

    Carl Lange was the founding father of neurology in Denmark, authoring several pioneering works within this field; however, these remained largely unknown internationally as he did not have them translated into a major language. He became a pioneer of psychophysiology with his contribution to the so-called James-Lange theory of emotion. His treatise on'periodical depressions' ('the Lange theory of depressions', 1886), is not only an early historical landmark but also a masterly 'modern' description concerning the nosology and nosography of recurrent depressions. Moreover, it is a landmark in the early history of lithium therapy, sadly ignored by Lange's contemporaries, but which little more than half a century later, with Cade's rediscovery of lithium's therapeutic effect in mood disorders in 1949, ushered in modern psychopharmacology.

  8. GaAs monolithic Lange and Wilkinson couplers

    NASA Astrophysics Data System (ADS)

    Waterman, R. C., Jr.; Fabian, W.; Pucel, R. A.; Tajima, Y.; Vorhaus, J. L.

    1981-02-01

    A monolithic GaAs X-band three-port Wilkinson coupler and a monolithic GaAs X-band four-port interdigitated Lange coupler are examined with reference to their design, fabrication technology, and experimental performance data. It is shown that fabrication of these couplers is compatible with present MMIC technologies. Measured loss minus fixture contributions is 0.25 dB and 0.75 dB for the Wilkinson and the Lange couplers, respectively.

  9. Characteristics of CdLS (Cornelia de Lange Syndrome)

    MedlinePlus

    ... individuals with CdLS strongly resemble one another. Typical facial features include thin eyebrows that meet in the ... have also been noted. Secondary Characteristics of CdLS Facial Features Prominent facial features include thin eyebrows that ...

  10. Kaj Ulrik Linderstrøm-Lang (1896-1959).

    PubMed Central

    Schellman, J. A.; Schellman, C. G.

    1997-01-01

    The Carlsberg Laboratory in Copenhagen has had a long tradition of outstanding science. At the time covered by this discussion, Kjeldahl, Sørensen, and Linderstrøm-Lang had been consecutive directors of the Chemical Laboratory for 83 years. Lang's inspired leadership began in the 1930s with a number of innovations (study of metabolism in single cells, titrations in non-aqueous solvents, relation of proteolysis to structure) but it was not until the early 1950s that Denmark had sufficiently recovered from the war for the laboratory to enter world science again. During World War II, Lang had been active in the Danish resistance movement. After the war, a number of major advances were being made that would revolutionize the field of protein chemistry (Pauling and Corey's H-bonded structures, Sanger's sequencing techniques, chromatography, Watson and Crick structures, modern instrumentation). The time for the new field of the physical biochemistry of proteins had arrived. Lang, with his broad experience, adventurous spirit, and genius for innovation, created an environment that was ideal for the convergence of these disconnected advances into a uniform science. The emphasis was to be on quantitative measurements on proteins in solution with interpretations based on molecular structures. During an all-too-brief period of time, Lang's laboratory attracted a large fraction of those who were destined to be the leaders of the next generation of protein chemists. At this time, the Carlsberg Laboratory was probably the most scientifically exciting environment for a protein chemist. The methods developed at that time-hydrogen exchange, limited proteolysis, optical rotatory dispersion, volume changes accompanying protein reactions, automatic titrations-are still all in common use and many of the visitors to the laboratory in that period and their students are still playing major roles in protein research. Lang's other qualities should not be ignored. He was not only a great

  11. Listening, Looking, and Learning with MacLang.

    ERIC Educational Resources Information Center

    Frommer, Judith

    1989-01-01

    Describes how the capabilities of the MacLang authoring system allow foreign language teachers to develop computer-assisted instruction that meets the listening skill objectives of foreign language courses. Examples are given of the use of audio and video interfaces that facilitate listening comprehension. (Author/CB)

  12. The complete mitochondrial genome of the Huang Lang chicken.

    PubMed

    Yu, Qi-Fang; Liu, Li-Li; Fu, Chen-Xing; He, Shao-Ping; Li, Si; He, Jian-Hua

    2016-01-01

    Huang Lang chicken is the native breed of Hunan province in China. The complete mitochondrial (mt) genome sequence plays an important role in the accurate determination of phylogenetic relationships among metazoans. It is the first time that the complete mt genome sequence of the Huang Lang chicken was reported in this work, which was determined through the polymerase chain reaction-based method. The total length of the mitogenome is 16,786 bp, with the base composition of 30.25% for A, 23.71% for T, 32.53% for C and 13.51% for G, in the order C > A > T > G feature occurs in the Huang Lang chicken. It contains the typical structure, including two ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The complete mt genome sequence of the Huang Lang chicken provided an important data for further study on the genetic mechanism.

  13. Rare Diseases Leading to Childhood Glaucoma: Epidemiology, Pathophysiogenesis, and Management

    PubMed Central

    Abdolrahimzadeh, Solmaz; Fameli, Valeria; Mollo, Roberto; Contestabile, Maria Teresa; Perdicchi, Andrea; Recupero, Santi Maria

    2015-01-01

    Noteworthy heterogeneity exists in the rare diseases associated with childhood glaucoma. Primary congenital glaucoma is mostly sporadic; however, 10% to 40% of cases are familial. CYP1B1 gene mutations seem to account for 87% of familial cases and 27% of sporadic cases. Childhood glaucoma is classified in primary and secondary congenital glaucoma, further divided as glaucoma arising in dysgenesis associated with neural crest anomalies, phakomatoses, metabolic disorders, mitotic diseases, congenital disorders, and acquired conditions. Neural crest alterations lead to the wide spectrum of iridocorneal trabeculodysgenesis. Systemic diseases associated with childhood glaucoma include the heterogenous group of phakomatoses where glaucoma is frequently encountered in the Sturge-Weber syndrome and its variants, in phakomatosis pigmentovascularis associated with oculodermal melanocytosis, and more rarely in neurofibromatosis type 1. Childhood glaucoma is also described in systemic disorders of mitotic and metabolic activity. Acquired secondary glaucoma has been associated with uveitis, trauma, drugs, and neoplastic diseases. A database research revealed reports of childhood glaucoma in rare diseases, which do not include glaucoma in their manifestation. These are otopalatodigital syndrome, complete androgen insensitivity, pseudotrisomy 13, Brachmann-de Lange syndrome, acrofrontofacionasal dysostosis, caudal regression syndrome, and Wolf-Hirschhorn syndrome. PMID:26451378

  14. Arc Magma Genesis from Melting of Mélange Diapirs

    NASA Astrophysics Data System (ADS)

    Cruz-Uribe, A. M.; Marschall, H.; Gaetani, G. A.

    2015-12-01

    Alkaline basalts occur in many subduction-related volcanic settings, including the Sunda, Izu-Bonin, Honshu, Aeolian, and Aleutian arcs, yet their origin continues to be debated. Recent studies have suggested that buoyant material (mélange) from the slab-wedge interface may rise into the hot corner of the mantle wedge as low-density plumes or diapirs, where it will melt or induce mantle melting due to dehydration. High-pressure mélange rocks represent a mixture of mafic, ultramafic, and sedimentary components, and are often dominated by chlorite. Mélange rocks are also enriched in accessory phases such as monazite, zircon, and rutile, which host a variety of trace elements. We present results from experimental melting of chlorite-rich mélange material at mantle wedge conditions that reproduce many of the compositional features of subduction-related lavas. Piston cylinder experiments were performed at conditions appropriate for mantle wedge diapirs (1030-1280 °C, 1.5-2.5 GPa) using natural mélange rocks from Syros, Greece. Experimental melts derived from omphacite-epidote-phengite bearing chlorite schists range in composition from basaltic trachyandesites to trachydacites to more alkaline melt compositions (50.7-60.73 wt% SiO2, 7.48-12.93 wt% Na2O+K2O). All of the experimental melts are characterized by high alumina contents (16.79-21.36 wt% Al2O3). Minerals coexisting with these melts include clinopyroxene, amphibole (at lower T) or olivine (at higher T), garnet (at higher P), ilmenite and/or rutile, and zircon. Trace element patterns in our experimentally produced melts are similar to those from arc volcanoes worldwide. Experimental melts are enriched in large ion lithophile elements (Cs, Rb, Ba, K, Pb, Sr) and depleted in high field strength elements (Nb, Ta, and Ti). Zirconium and Hf are enriched relative to the rare earth elements (REE), which show flat to heavy REE depleted patterns depending on the presence of residual garnet. Thorium is fractionated

  15. Genes and Syndromic Hearing Loss.

    ERIC Educational Resources Information Center

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  16. Genes and Syndromic Hearing Loss.

    ERIC Educational Resources Information Center

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  17. Discrete Lange-Newell criterion for dissipative systems

    NASA Astrophysics Data System (ADS)

    Ndzana, Fabien, II; Mohamadou, Alidou; Kofané, Timoleon Crépin

    2009-05-01

    We report on the derivation of the discrete complex Ginzburg-Landau equation with first- and second-neighbor couplings using a nonlinear electrical network. Furthermore, we discuss theoretically and numerically modulational instability of plane carrier waves launched through the line. It is pointed out that the underlying analysis not only spells out the discrete Lange-Newell criterion by the means of the linear stability analysis at which the modulational instability occurs for the generation of a train of ultrashort pulses, but also characterizes the long-time dynamical behavior of the system when the instability grows.

  18. Discrete Lange-Newell criterion for dissipative systems.

    PubMed

    Ndzana, Fabien I I; Mohamadou, Alidou; Kofané, Timoleon Crépin

    2009-05-01

    We report on the derivation of the discrete complex Ginzburg-Landau equation with first- and second-neighbor couplings using a nonlinear electrical network. Furthermore, we discuss theoretically and numerically modulational instability of plane carrier waves launched through the line. It is pointed out that the underlying analysis not only spells out the discrete Lange-Newell criterion by the means of the linear stability analysis at which the modulational instability occurs for the generation of a train of ultrashort pulses, but also characterizes the long-time dynamical behavior of the system when the instability grows.

  19. Evolution of Ice Mélange Motion During Periods of Terminus Quiescence

    NASA Astrophysics Data System (ADS)

    Cassotto, R.; Amundson, J. M.; Fahnestock, M. A.; Truffer, M.; Burton, J. C.; Kuo, C. C.; Dennin, M.; Boettcher, M. S.

    2016-12-01

    Variations in the strength of ice mélange, a dense matrix of icebergs and sea ice retained in many proglacial fjords, has been proposed as a key process influencing the stability of tidewater glaciers in Greenland [Straneo et al., 2013]. Several observational studies have shown that variations in ice mélange characteristics often precede changes in speed and calving rates along glacier termini. A full understanding of the resistance provided by ice mélange, and therefore its impact on glacier stability, requires knowledge of its granular rheology. Toward this goal, we present unique terrestrial radar interferometry (TRI) observations of the ice mélange at Jakobshavn Isbræ, Greenland that was acquired at very high spatial (meters) and temporal (minutes) resolution during summer 2012. Data was collected over a 15-day period, during which several large calving events occurred. Previous work [Peters et al., 2015] described the dynamic jamming of the ice mélange that was observed during calving events. Here, we focus on the more gradual evolution of the ice mélange during periods of terminus quiescence. We look at variations in velocity and strain rate and consider how glacier motion, ocean currents, tides, and wind affect motion of the ice mélange. Our aim is to provide the most comprehensive study of ice mélange rheology to date.

  20. Design of Microstrip Lange Coupler Based on Em-Ann Model

    NASA Astrophysics Data System (ADS)

    Yang, Ziqiang; Yang, Tao; Liu, Yu

    2006-10-01

    Electromagnetically trained artificial neural network (EM-ANN) model for microstrip Lange Coupler is presented. Full-wave EM analysis software is employed to characterize the Lange Coupler. The EM-ANN model is then designed using physical parameters as inputs and S-parameters as outputs. Once the EM-ANN model is trained, it can be used to find the optimal physical structure of the Lange Coupler for a given application using optimization technique. A Ka-band microstrip Lange Coupler is designed by this method. The simulated results of the Lange Coupler show that the insert loss is better than -3.64 dB; the amplitude balance is less than 0.55 dB and the phase balance is less than 0.52°from the 90°phase difference over the 30 to 40 GHz frequency range.

  1. Genesis of the Batinah mélange above the Semail ophiolite, Oman

    NASA Astrophysics Data System (ADS)

    Robertson, A. H. F.; Woodcock, N. H.

    The Batinah mélange which overlies the late Cretaceous Semail ophiolite in the northern Oman Mountains comprises mostly sedimentary rocks of deep-water facies, alkalic lavas and intrusives, all of continental margin affinities, together with smaller volumes of Semail ophiolitic and metamorphic rocks. Four intergradational textural types of mélange can be recognized. Sheet mélange has large (>1 km) intact sheets either with little intervening matrix or set in other mélange types, and with an organised sheet orientation fabric. Slab mélange is finer textured (>100 m) and more disrupted. Block mélange has smaller (> m) blocks with some matrix and a weak to random block fabric. Clast mélange is matrix-supported rudite with a weak depositional clast fabric. Structural relationships, particularly the absence of tectonic fabrics, the decreasing strength of fragment fabrics with increasing fragmentation, and the abundance of brittle fragmentation, suggest that these mélange types formed by either gravity-driven sedimentary processes or superficial sliding or thrusting of individual rock slabs. In the slab mélange, long sequences can be pieced together, passing up from Upper Triassic mafic sub-marine extrusives and sediments into radiolarian cherts, hemipelagic and redeposited limestones, and terminating in non-calcareous radiolarities with Mn-deposits of early Cretaceous age. Mafic sills are numerous. These sequences can be matched with sub-ophiolite rocks now exposed in fault corridors through the Semail. These sequences become progressively disrupted upwards in the corridors and can be traced continuously into overlying mélange, which then thins away from the corridors. We argue that, during late Cretaceous emplacement over the Arabian margin, active fault corridors split the Semail slab and acted as conduits up which sub-ophiolite rocks were supplied to the ophiolite surface. There the rocks were redisributed by superficial processes.

  2. Conformal symmetry of the Lange-Neubert evolution equation

    NASA Astrophysics Data System (ADS)

    Braun, V. M.; Manashov, A. N.

    2014-04-01

    The Lange-Neubert evolution equation describes the scale dependence of the wave function of a meson built of an infinitely heavy quark and light antiquark at light-like separations, which is the hydrogen atom problem of QCD. It has numerous applications to the studies of B-meson decays. We show that the kernel of this equation can be written in a remarkably compact form, as a logarithm of the generator of special conformal transformation in the light-ray direction. This representation allows one to study solutions of this equation in a very simple and mathematically consistent manner. Generalizing this result, we show that all heavy-light evolution kernels that appear in the renormalization of higher-twist B-meson distribution amplitudes can be written in the same form.

  3. Thinning sea ice weakens buttressing force of iceberg mélange and promotes calving

    NASA Astrophysics Data System (ADS)

    Robel, Alexander A.

    2017-03-01

    At many marine-terminating glaciers, the breakup of mélange, a floating aggregation of sea ice and icebergs, has been accompanied by an increase in iceberg calving and ice mass loss. Previous studies have argued that mélange may suppress calving by exerting a buttressing force directly on the glacier terminus. In this study, I adapt a discrete element model to explicitly simulate mélange as a cohesive granular material. Simulations show that mélange laden with thick landfast sea ice produces enough resistance to shut down calving at the terminus. When sea ice within mélange thins, the buttressing force on the terminus is reduced and calving is more likely to occur. When a calving event does occur, it initiates a propagating jamming wave within mélange, which causes local compression and then slow mélange expansion. The jamming wave can also initiate widespread fracture of sea ice and further increase the likelihood of subsequent calving events.

  4. Thinning sea ice weakens buttressing force of iceberg mélange and promotes calving.

    PubMed

    Robel, Alexander A

    2017-03-01

    At many marine-terminating glaciers, the breakup of mélange, a floating aggregation of sea ice and icebergs, has been accompanied by an increase in iceberg calving and ice mass loss. Previous studies have argued that mélange may suppress calving by exerting a buttressing force directly on the glacier terminus. In this study, I adapt a discrete element model to explicitly simulate mélange as a cohesive granular material. Simulations show that mélange laden with thick landfast sea ice produces enough resistance to shut down calving at the terminus. When sea ice within mélange thins, the buttressing force on the terminus is reduced and calving is more likely to occur. When a calving event does occur, it initiates a propagating jamming wave within mélange, which causes local compression and then slow mélange expansion. The jamming wave can also initiate widespread fracture of sea ice and further increase the likelihood of subsequent calving events.

  5. Emotional Mental Imagery as Simulation of Reality: Fear and Beyond-A Tribute to Peter Lang.

    PubMed

    Ji, Julie L; Heyes, Stephanie Burnett; MacLeod, Colin; Holmes, Emily A

    2016-09-01

    This article pays tribute to the seminal paper by Peter J. Lang (1977; this journal), "Imagery in Therapy: Information Processing Analysis of Fear." We review research and clinical practice developments in the past five decades with reference to key insights from Lang's theory and experimental work on emotional mental imagery. First, we summarize and recontextualize Lang's bio-informational theory of emotional mental imagery (1977, 1979) within contemporary theoretical developments on the function of mental imagery. Second, Lang's proposal that mental imagery can evoke emotional responses is evaluated by reviewing empirical evidence that mental imagery has a powerful impact on negative as well as positive emotions at neurophysiological and subjective levels. Third, we review contemporary cognitive and behavioral therapeutic practices that use mental imagery, and consider points of extension and departure from Lang's original investigation of mental imagery in fear-extinction behavior change. Fourth, Lang's experimental work on emotional imagery is revisited in light of contemporary research on emotional psychopathology-linked individual differences in mental imagery. Finally, key insights from Lang's experiments on training emotional response during imagery are discussed in relation to how specific techniques may be harnessed to enhance adaptive emotional mental imagery training in future research.

  6. Thinning sea ice weakens buttressing force of iceberg mélange and promotes calving

    PubMed Central

    Robel, Alexander A.

    2017-01-01

    At many marine-terminating glaciers, the breakup of mélange, a floating aggregation of sea ice and icebergs, has been accompanied by an increase in iceberg calving and ice mass loss. Previous studies have argued that mélange may suppress calving by exerting a buttressing force directly on the glacier terminus. In this study, I adapt a discrete element model to explicitly simulate mélange as a cohesive granular material. Simulations show that mélange laden with thick landfast sea ice produces enough resistance to shut down calving at the terminus. When sea ice within mélange thins, the buttressing force on the terminus is reduced and calving is more likely to occur. When a calving event does occur, it initiates a propagating jamming wave within mélange, which causes local compression and then slow mélange expansion. The jamming wave can also initiate widespread fracture of sea ice and further increase the likelihood of subsequent calving events. PMID:28248285

  7. Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype.

    PubMed

    Parenti, I; Gervasini, C; Pozojevic, J; Graul-Neumann, L; Azzollini, J; Braunholz, D; Watrin, E; Wendt, K S; Cereda, A; Cittaro, D; Gillessen-Kaesbach, G; Lazarevic, D; Mariani, M; Russo, S; Werner, R; Krawitz, P; Larizza, L; Selicorni, A; Kaiser, F J

    2016-01-01

    Cornelia de Lange syndrome (CdLS) and KBG syndrome are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, and some craniofacial and limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified in at least 70% of the patients with CdLS. Consequently, additional causative genes, either unknown or responsible of partially merging entities, possibly account for the remaining 30% of the patients. In contrast, KBG has only been associated with mutations in ANKRD11. By exome sequencing we could identify heterozygous loss-of-function mutations in ANKRD11 in two patients with the clinical diagnosis of CdLS. Both patients show features reminiscent of CdLS such as characteristic facies as well as a small head circumference which is not described for KBG syndrome. Patient A, who carries the mutation in a mosaic state, is a 4-year-old girl with features reminiscent of CdLS. Patient B, a 15-year-old boy, shows a complex phenotype which resembled CdLS during infancy, but has developed to a more KBG overlapping phenotype during childhood. These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Design And Performance Of 20 And 45 GHZ MMIC Lange Couplers

    NASA Astrophysics Data System (ADS)

    Wallace, Jack E.; Ellis, Grant A.

    1988-11-01

    Experimental results are presented for GaAs MMIC Lange coupler designs in both the 15 to 25 GHz and 33 to 50 GHz frequency ranges. Coupler insertion loss, return loss, isolation, and differential insertion phase are included.

  9. In Praise of Dissidence: Anne Lang-Etienne (1932-1991). Muriel Driver Memorial Lecture.

    ERIC Educational Resources Information Center

    Thibeault, Rachel

    2002-01-01

    Discusses the life and work of Anne Lang-Etienne, a dissident occupational therapist who moved and shaped a generation of Canadian therapists and spurred the profession to action for social change. Includes 18 references. (JOW)

  10. The origin of mélanges: Cautionary tales from Indonesia

    NASA Astrophysics Data System (ADS)

    Barber, A. J.

    2013-10-01

    The origin of block-in-matrix mélanges has been the subject of intense speculation by structural and tectonic geologists working in accretionary complexes since their first recognition in the early twentieth century. Because of their enigmatic nature, a number of important international meetings and a large number of publications have been devoted to the problem of the origin of mélanges. As mélanges show the effects of the disruption of lithological units to form separate blocks, and also apparently show the effects shearing in the scaly fabric of the matrix, a tectonic origin has often been preferred. Then it was suggested that the disruption to form the blocks in mélanges could also occur in a sedimentary environment due to the collapse of submarine fault scarps to form olistostromes, upon which deformation could be superimposed tectonically. Subsequently it has proposed that some mélanges have originated by overpressured clays rising buoyantly towards the surface, incorporating blocks of the overlying rocks in mud or shale diapirs and mud volcanoes. Two well-known examples of mélanges from the Banda and Sunda arcs are described, to which tectonic and sedimentary origins were confidently ascribed, which proved on subsequent examination to have been formed due to mud diapirism, in a dynamically active environment, as the result of tectonism only indirectly. Evidence from the Australian continental Shelf to the south of Sumba shows that large quantities of diapiric mélange were generated before the diapirs were incorporated in the accretionary complex. Comparable diapirs can be recognised in Timor accreted at an earlier stage. Evidence from both Timor and Nias shows that diapiric mélange can be generated well after the initial accretion process was completed. The problem is: Why, when diapirism is so abundantly found in present convergent margins, is it so rarely reported from older orogenic belts? Many occurrences of mélanges throughout the world to

  11. Jamming of granular ice mélange in tidewater glacial fjords

    NASA Astrophysics Data System (ADS)

    Burton, J. C.; Cassotto, R.; Amundson, J. M.; Kuo, C. C.; Dennin, M.

    2016-12-01

    In tidewater glacial fjords, the open water in front of the glacier terminus is often filled with a collection of calved iceberg fragments and sea ice. For glaciers with large calving rates, this "mélange" of ice can be jam-packed, so that the flow is mostly determined by granular interactions, in addition to underlying fjord currents. As the glacier pushes the ice mélange through the fjord, the mélange will become jammed and may potentially influence calving rates if the back-stress applied to the glacier terminus is large enough. However, the stress applied by a granular ice mélange will depend on its rheology, i.e. iceberg-iceberg contact forces, geometry, friction, etc. Here we report 2D, discrete particle simulations to model the granular mechanics of ice mélange. A polydisperse collection of particles is packed into a long channel and pushed downfjord at a constant speed, the latter derived from terrestrial radar interferometry (TRI). Each individual particle experiences viscoelastic contact forces and tangential frictional forces upon collision with another particle or channel walls. We find the two most important factors that govern the total force applied to the glacier are the geometry of the channel, and the shape of the particles. In addition, our simulated velocity fields reveal shearing margins near the fjord walls with more uniform flow in the middle of the mélange, consistent with TRI observations. Finally, we find that the magnitude of the back-stress applied to the glacier terminus can influence calving, however, the maximum back-stress is limited by the buckling of icebergs into the fjord waters, so that the stress in the quasi-2D mélange is partially determined by the thickness of the mélange layer.

  12. The origin and tectonic significance of mélanges in Eastern Sabah, Malaysia

    NASA Astrophysics Data System (ADS)

    Clennell, Ben

    Extensive chaotically disrupted rock bodies are found across Sabah in diverse tectonic settings. These units, which include broken formations, a dismembered arc-ophiolite complex and mud-matrix mélanges were formed by a combination of sedimentary, tectonic and diapiric processes. The mélanges of the eastern part of Sabah are considered to be related to basin initiation in an intra-arc setting, and are not related directly to subduction-accretion processes. The East Sabah mélanges are composed predominantly of deep water clastic sediments, deposited in the Central Sabah Basin, mixed with varying amounts of exotic ophiolitic material. The sedimentary clasts have a variety of well-developed "soft-sediment" deformation structures. These are in part inherited into the mélange from syn-sedimentary deformation, and in part generated during the mélange-forming events. The mélanges are not metamorphosed, and vitrinite reflectance data suggest that except for a few localities, a maximum temperature of less than 120°C was attained in the matrix. The ophiolitic blocks commonly have tectonic shearing fabrics associated with low temperature metamorphism. These metamorphic fabrics are incompatible with the deformation mechanisms in the sedimentary clasts and the mud matrix, and are interpreted as being inherited from shear in the ocean floor environment (e.g. fracture zones) or associated with ophiolite obduction. The similarity in clast type, deformation history and general structure also suggest that all the mélanges of the east of Sabah were formed in a series of related events during late Early Miocene and earliest Middle Miocene time. It is postulated that these events, which triggered sedimentary, diapiric and tectonic mélange-forming processes, are related to the coeval onset of extension and sea floor spreading in the southeastern Sulu Sea.

  13. Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation.

    PubMed

    Baquero-Montoya, Carolina; Gil-Rodríguez, María-Concepción; Hernández-Marcos, María; Teresa-Rodrigo, María-Esperanza; Vicente-Gabas, Alicia; Bernal, María-Luisa; Casale, Cesar-Horacio; Bueno-Lozano, Gloria; Bueno-Martínez, Inés; Queralt, Ethel; Villa, Olaya; Hernando-Davalillo, Cristina; Armengol, Lluís; Gómez-Puertas, Paulino; Puisac, Beatriz; Selicorni, Angelo; Ramos, Feliciano J; Pié, Juan

    2014-09-01

    Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Flow behavior of ice mélange modeled at the laboratory-scale

    NASA Astrophysics Data System (ADS)

    Kuo, C. C.; Amundson, J. M.; Cassotto, R.; Burton, J. C.; Dennin, M.

    2016-12-01

    Ice mélange, composed of icebergs from iceberg calving and sea ice, is a large-scale, quasi-two dimensional granular system that may affect glacier stability by resisting iceberg calving. The motion of ice mélange is a result of inter-particle interactions between icebergs which are affected by ice mélange composition, fjord geometry, and driving forces. One of the significant features of this highly complex system is stick-slip flow that occurs as icebergs slide past each other. Here, we report on laboratory simulations of ice mélange motion. Plastic particles of various geometries are placed on the water surface in a meter-long channel and forced down the channel by a moving barrier. Our studies are focused on the impact of particle shapes, size distributions, and channel geometry on the flow behavior. The velocity fields of the experiments are analyzed and compared to numerical simulations and field observations. We relate the flow behavior to the back-stress provided by ice mélange, and find that it depends strongly on particle shape and channel geometry.

  15. Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity

    ERIC Educational Resources Information Center

    Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

    2011-01-01

    We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in…

  16. Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity

    ERIC Educational Resources Information Center

    Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

    2011-01-01

    We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in…

  17. Development of tectono-sedimentary mélanges in accretionary wedges: Insights from analog modeling

    NASA Astrophysics Data System (ADS)

    Genti, M.; Malavieille, J.; Molli, G.; Dominguez, S.; Taboada, A.; Vitale-Brovarone, A.

    2012-04-01

    Orogenic wedges locally present chaotic tectonostratigraphic units that contain exotic blocks of various size, origin, age and lithology, embedded in a sedimentary matrix. The occurrence of ophiolitic blocks, sometimes huge, in such "mélanges" raises questions on i) the mechanisms responsible for the incorporation of oceanic basement rocks into an accretionary wedge and ii) the mechanisms allowing exhumation and possibly redeposition of these exotic elements in "mélanges" during wedge growth. The tectonic evolution of the back part of doubly vergent accretionary wedges is mainly controled by backthrusting. The retrowedge is characterized by steep slopes that are prone to gravitational instabilities. We assume that these steep slopes trigger submarine landslides playing a major erosional role and therefore inducing huge mass transfers. This erosion allows exhumation of the ophiolitic fragments formerly accreted at the base of the wedge and then reworked as tectono-sedimentary "mélanges" redeposited in proximal basins located at the base of the retrowedge slope. These basin deposits are then continuously involved in backthrusting-induced deformation. In this study, we present the results of a series of analog experiments performed to characterize the processes and parameters responsible for accretion, exhumation and final tectonosedimentary reworking of oceanic basement lithosphere fragments in an accretionary wedge. The experimental setup is designed to simulate the interaction between tectonics, erosion and sedimentation. Different configurations are applied to study the impact of various parameters, such as irregular oceanic floor due to structural inheritance, or the presence of layers with contrasted rheology that can affect deformation partitioning in the wedge (frontal accretion vs basal accretion) influencing its growth. The experimental results are then compared with observations on ophiolite-bearing mélanges in the Taïwan (Lichi mélange) and northern

  18. Mechanical impact of sea-ice/mélange on marine terminating glaciers

    NASA Astrophysics Data System (ADS)

    Lindsey, D. S.; Dupont, T. K.

    2011-12-01

    Observations indicate that large portions of ice-sheet margins are currently undergoing rapid dynamic change. The role of the ocean and sea-ice in altering glacier dynamics is currently an active field of research. Sea-ice, along with encased icebergs and marine ice (known as mélange), has been hypothesized to potentially affect glacier calving rates. In winter, sea-ice forms, stiffening the mélange, forming something akin to a thin ice-shelf. In an embayment, the sea-ice/mélange connects embayment walls to the glacial terminus potentially weakening longitudinal strain-rates. As calving rates are strongly dependent on longitudinal strain-rates, a decrease in strain-rate decreases calving. In certain cases decreased calving can lead to a terminus advance resulting in increased lateral drag and decreased glacier velocity. The outlined process is one of several competing theories that help explain the winter terminus advance and associated decrease in velocity at Jakobshavn Isbræ in Greenland. This work assesses the potential mechanical impact sea-ice/mélange (referred hereafter as winter mélange) can have on glacier dynamics. We examine the conditions under which winter mélange can have a significant impact on longitudinal strain-rates. We utilize two calving parameterizations, one depending on ice strain-rate, and the other based on a crevasse depth criterion. Results are presented from a 1-D force balance analysis and 2D plan-view diagnostic model. The 2D model explicitly incorporates the winter mélange as a thin shelf of uniform thickness within the interior of the domain. The model can account for variations in density, thickness, and ice hardness between glacier and winter mélange. Several questions ultimately drive this research. Under what geometric and rheological conditions can winter mélange affect longitudinal strain-rates? How sensitive is the calving rate to a decrease in glacier strain-rate? More specifically, can a small change in

  19. The Prevalence and Phenomenology of Repetitive Behavior in Genetic Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Oliver, Chris; Arron, Kate; Burbidge, Cheryl; Berg, Katy

    2009-01-01

    We investigated the prevalence and phenomenology of repetitive behavior in genetic syndromes to detail profiles of behavior. The Repetitive Behaviour Questionnaire (RBQ) provides fine-grained identification of repetitive behaviors. The RBQ was employed to examine repetitive behavior in Angelman (N = 104), Cornelia de Lange (N = 101), Cri-du-Chat…

  20. The Prevalence and Phenomenology of Repetitive Behavior in Genetic Syndromes

    ERIC Educational Resources Information Center

    Moss, Joanna; Oliver, Chris; Arron, Kate; Burbidge, Cheryl; Berg, Katy

    2009-01-01

    We investigated the prevalence and phenomenology of repetitive behavior in genetic syndromes to detail profiles of behavior. The Repetitive Behaviour Questionnaire (RBQ) provides fine-grained identification of repetitive behaviors. The RBQ was employed to examine repetitive behavior in Angelman (N = 104), Cornelia de Lange (N = 101), Cri-du-Chat…

  1. From Tappan to Lange: Evolution of the Public Junior College Idea.

    ERIC Educational Resources Information Center

    Gallagher, Edward Arthur

    This study is a historical analysis of the public junior college idea and its emergence. The thoughts and actions of Henry P. Tappan, William W. Folwell, William R. Harper, David S. Jordan, and Alexis Lange contributed most to its origin and development. These men, products of the late nineteenth and early twentieth centuries, were strongly…

  2. Friedrich Albert Lange on neo-Kantianism, socialist Darwinism, and a psychology without a soul.

    PubMed

    Teo, Thomas

    2002-01-01

    Friedrich Albert Lange was a German philosopher, political theorist, educator, and psychologist who outlined an objective psychology in the 1860s. This article shows how some of the most important worldviews of the nineteenth century (Kantianism, Marxism, and Darwinism) were combined creatively in his thought system. He was crucial in the development of neo-Kantianism and incorporated psycho-physiological research on sensation and perception in order to defend Kant's epistemological idealism. Based on a critique of phrenology and philosophical psychology of his time, Lange developed a program of a psychology without a soul. He suggested that only those phenomena that can be observed and controlled should be studied, that psychology should focus on actions and speech, and that for each psychological event the corresponding physical or physiological processes should be identified. Lange opposed introspection and subjective accounts and promoted experiments and statistics. He also promoted Darwinism for psychology while developing a socialist progressive-democratic reading of Darwin in his social theory. The implications of socialist Darwinism on Lange's conceptualization of race are discussed and his prominence in nineteenth century philosophy and psychology is summarized. Copyright 2002 Wiley Periodicals, Inc.

  3. Foreign Language Authoring Systems: Judith Frommer's MacLang Spoken Here.

    ERIC Educational Resources Information Center

    Frommer, Judith

    1987-01-01

    MacLang, a user-friendly authoring system for the Macintosh computer, helps second language teachers prepare and tailor computer exercises and activities; is usable with any Roman-alphabet language, Russian, and Greek; gives students intelligent feedback; and allows students to control computer activity in order to individualize learning.…

  4. Foreign Language Authoring Systems: Judith Frommer's MacLang Spoken Here.

    ERIC Educational Resources Information Center

    Frommer, Judith

    1987-01-01

    MacLang, a user-friendly authoring system for the Macintosh computer, helps second language teachers prepare and tailor computer exercises and activities; is usable with any Roman-alphabet language, Russian, and Greek; gives students intelligent feedback; and allows students to control computer activity in order to individualize learning.…

  5. Design of a 24-40 GHz balanced low noise amplifier using Lange couplers

    NASA Astrophysics Data System (ADS)

    Zongnan, Zhang; Qinghua, Huang; Mingli, Hao; Hao, Yang; Haiying, Zhang

    2009-04-01

    A wide band (24-40 GHz) fully integrated balanced low noise amplifier (LNA) using Lange couplers was designed and fabricated with a 0.15 μm pseudomorphic HEMT (pHEMT) technology. A new method to design a low-loss and high-coupling Lange coupler for wide band application in microwave frequency was also presented. This Lange coupler has a minimum loss of 0.09 dB and a maximum loss of 0.2 dB over the bandwidth from 20 to 45 GHz. The measured results show that the realized four-stage balanced LNA using this Lange coupler exhibites a noise figure (NF) of less than 2.7 dB and the maximum gain of 30 dB; moreover, a noticeably improved reflection performance is achieved. The input VSWR and the output VSWR are respectively less than 1.45 and 1.35 dB across the 24-40 GHz frequency range.

  6. Horizontal lang two-pencil test as a screening test for stereopsis and binocularity

    PubMed Central

    Nongpiur, Monisha E; Sharma, Pradeep

    2010-01-01

    Purpose: To assess the horizontal Lang two-pencil test as a bedside test to detect gross stereopsis. Materials and Methods: Eighty-four strabismic subjects divided into two groups based on the amount of deviation, and 40 normal subjects were studied. Sensory status examination including binocularity and stereopsis were evaluated with Bagolini, Titmus test and the Netherlands organisation for applied scientific research (TNO), Randot, synoptophore and horizontal Lang two-pencil test. Results: The subjects in the group with smaller deviation showed better performance on all the four stereo tests and over 90% demonstrated presence of fusion. When compared to TNO and Randot for determining presence of stereopsis, the horizontal Lang two-pencil test demonstrated sensitivity of 100% and 83.9%, specificity of 77.8% and 73.7%, and negative predictive value of 100% and 100% respectively. It also showed 100% specificity as a test for binocularity when compared with the Bagolini striated glass test. Conclusion: Horizontal Lang two-pencil test, an easily performed test with a high sensitivity and negative predictive value can be used as a screening test to detect gross stereopsis and binocularity. PMID:20534917

  7. From Tappan to Lange: Evolution of the Public Junior College Idea.

    ERIC Educational Resources Information Center

    Gallagher, Edward Arthur

    This study is a historical analysis of the public junior college idea and its emergence. The thoughts and actions of Henry P. Tappan, William W. Folwell, William R. Harper, David S. Jordan, and Alexis Lange contributed most to its origin and development. These men, products of the late nineteenth and early twentieth centuries, were strongly…

  8. The Varieties of Emotional Experience: A Meditation on James-Lange Theory.

    ERIC Educational Resources Information Center

    Lang, Peter J.

    1994-01-01

    This article traces the origin of the James-Lange theory of emotion, considers differences in their thinking, and assesses early criticisms and debate. Research on physiological patterns in emotion is reviewed. New paths for emotion research are outlined and homage is paid to the inspiration of William James. (SLD)

  9. Could Separate Be Equal? Helene Lange and Women's Education in Imperial Germany.

    ERIC Educational Resources Information Center

    Albisetti, James C.

    1982-01-01

    Helene Lange worked to obtain equal educational opportunities for women in Germany at the end of the nineteenth century. She tried to improve teacher training for women, enhance the curriculum in girls' high schools, and increase professional training opportunities for women. (AM)

  10. "Moving Education Forward to Keep Society Back": The South African De Lange Report Reevaluated.

    ERIC Educational Resources Information Center

    Collins, Colin B.; Gillespie, Roselyn R.

    1984-01-01

    The "De Lange Report" (1981) is the third major report on education to appear in South Africa, is by far the most comprehensive and detailed in both stated and implied assertions, poses the educational problem as technicist/manpower questions, and should be seen as part of South Africa's total strategy policy. (BRR)

  11. Carer-Reported Contemporary Health Problems in People with Severe and Profound Intellectual Disability and Genetic Syndromes

    ERIC Educational Resources Information Center

    Berg, Katy; Arron, Kate; Burbidge, Cheryl; Moss, Joanna; Oliver, Chris

    2007-01-01

    Identifying health problems in people with severe and profound disabilities and genetic syndromes can be problematic, and unidentified or unmanaged health problems may adversely impact an individual's quality of life. The authors studied carer-reported contemporary health problems in three genetic syndromes (Angelman, Cornelia de Lange, and Cri du…

  12. Carer-Reported Contemporary Health Problems in People with Severe and Profound Intellectual Disability and Genetic Syndromes

    ERIC Educational Resources Information Center

    Berg, Katy; Arron, Kate; Burbidge, Cheryl; Moss, Joanna; Oliver, Chris

    2007-01-01

    Identifying health problems in people with severe and profound disabilities and genetic syndromes can be problematic, and unidentified or unmanaged health problems may adversely impact an individual's quality of life. The authors studied carer-reported contemporary health problems in three genetic syndromes (Angelman, Cornelia de Lange, and Cri du…

  13. The Ankara Mélange: an indicator of Tethyan evolution of Anatolia

    NASA Astrophysics Data System (ADS)

    Çakir, Üner; Üner, Tijen

    2016-08-01

    The Ankara Mélange is a complex formed by imbricated slices of limestone block mélanges (Karakaya and Hisarlıkaya Formations), Neotethyan ophiolites (Eldivan, Ahlat and Edige ophiolites), post-ophiolitic cover units (Mart and Kavak formations) and Tectonic Mélange Unit (Hisarköy Formation or Dereköy Mélange). The Karakaya and Hisarlıkaya formations are roughly similar and consist mainly of limestone block mélange. Nevertheless, they represent some important geological differences indicating different geological evolution. Consequently, the Karakaya and Hisarlıkaya formations are interpreted as Eurasian and Gondwanian marginal units formed by fragmentation of the Gondwanian carbonate platform during the continental rifting of the Neotethys in the Middle Triassic time. During the latest Triassic, Neotethyan lithosphere began to subduct beneath the Eurasian continent and caused intense deformation of the marginal units. The Eldivan, Ahlat and Edige ophiolites represent different fragments of the Neotethyan oceanic lithosphere emplaced onto the Gondwanian margin during the Albian-Aptian, middle Turonian and middle Campanian, respectively. The Eldivan Ophiolite is a NE-SW trending and a nearly complete assemblage composed, from bottom to top, of a volcanic-sedimentary unit, a metamorphic unit, peridotite tectonites, cumulates and sheeted dykes. The Eldivan Ophiolite is unconformably covered by Cenomanian-Lower Turonian sedimentary unit. The Eldivan Ophiolite is overthrust by the Ahlat Ophiolite in the north and Edige Ophiolite in the west. The Ahlat ophiolite is an east-west oriented assemblage comprised of volcanic-sedimentary unit, metamorphic unit, peridotite tectonites and cumulates. The Edige Ophiolite consists of a volcanic-sedimentary unit, peridotite tectonites, dunite, wherlite, pyroxenite and gabbro cumulates. The Tectonic Mélange Unit is a chaotic formation of various blocks derived from ophiolites, from the Karakaya and Hisarlıkaya formations and

  14. Effects of herbicides on Behr's metalmark butterfly, a surrogate species for the endangered butterfly, Lange's metalmark.

    PubMed

    Stark, John D; Chen, Xue Dong; Johnson, Catherine S

    2012-05-01

    Lange's metalmark butterfly, Apodemia mormo langei Comstock, is in danger of extinction due to loss of habitat caused by invasive exotic plants which are eliminating its food, naked stem buckwheat. Herbicides are being used to remove invasive weeds from the dunes; however, little is known about the potential effects of herbicides on butterflies. To address this concern we evaluated potential toxic effects of three herbicides on Behr's metalmark, a close relative of Lange's metalmark. First instars were exposed to recommended field rates of triclopyr, sethoxydim, and imazapyr. Life history parameters were recorded after exposure. These herbicides reduced the number of adults that emerged from pupation (24-36%). Each herbicide has a different mode of action. Therefore, we speculate that effects are due to inert ingredients or indirect effects on food plant quality. If these herbicides act the same in A. mormo langei, they may contribute to the decline of this species.

  15. Relating syntax and semantics: the syntactico-semantic lexicon of the system VIE-LANG

    SciTech Connect

    Steinacker, I.; Buchberger, E.

    1983-01-01

    This paper describes the structure and evaluation of the syntactico-semantic lexicon (SSL) of the German natural language understanding system VIE-LANG. VIE-LANG uses an si-net as internal representation. The SSL contains the rules according to which the mapping between net-structures and surface structures of a sentence is carried out. This information is structured in a way that it can be evaluated from two sides. The parser interprets it as production-rules that control the analysis. Syntactic and semantic features of the input sentence and evaluated and individuals are created in the semantic net. The generator uses the same rules to express selected net-structures in adequate natural language expressions. It is shown who both processes can make effective use of the SSL. The different possibilities for evaluating the SSL are explained and illustrated by examples. 12 references.

  16. Assessment of adult stereopsis using the Lang 1 Stereotest: a pilot study.

    PubMed

    Brown, S; Weih, L; Mukesh, N; McCarty, C; Taylor, H

    2001-01-01

    To assess the use of the Lang 1 Stereotest as a vision-screening test for adults, for which little is known or reported. The Lang 1 Stereotest was administered to 292 consecutive participants of the Visual Impairment Project (VIP) five year followup study, which is a population based study of eye disease in Melbourne, Australia. 56.9% were female. The mean age was 59.4 years, range 44-90 years. A "positive" stereoscopic response was recorded where the stereoscopic target image was correctly named; a "partial positive" response where depth was appreciated but the shape could not be named; and a "negative" response where there was no appreciation of a stereo effect. The responses were further categorized so that the test was either "passed" or "failed". A "pass" score was 3/3 positive responses; 3/3 partial positive responses or 2/3 positive and/or partial positive responses where the negative response was at the 550" of arc stereoacuity level. "Failure" was 3/3 negative responses and 2/3 negative responses where the positive or partial positive response as at the 1200" level. Of the 292 participants tested, 19 (6.5%) participants "failed" the test. In addition to strabismus and anisometropia, failure was associated significantly (p<0.001) with reduced distance visual acuity (<6/12) irrespective of the ocular morbidity. The Lang 1 Stereotest correctly identified people with vision defects associated with reduced stereopsis. This suggests the Lang 1 Stereotest is an appropriate for the vision screening of adults as it is for children.

  17. Relationship between magnetic fabrics and shear directions in mélange within the Miyama Formation, Shimanto accretionary complex, Japan

    NASA Astrophysics Data System (ADS)

    Tokiwa, Tetsuya; Yamamoto, Yuzuru

    2012-09-01

    The magnetic fabrics of tectonic mélange in the Miyama Formation, Shimanto accretionary complex of Kii Peninsula, Japan, are examined using anisotropy of magnetic susceptibility (AMS) data, and they are compared with shear directions estimated by traditional measurements of P-Y intersections in the mélange. In most cases, AMS data are consistent with the estimated shear directions, and they can be divided into two types: one with Kmax (the maximum magnetic susceptibility) axes oriented parallel to the shear direction on the shear planes, and another with Kmax axes oriented parallel to the P-Y intersections. In both types, the Kmin (the minimum magnetic susceptibility) axes are oriented perpendicular to the mélange foliation. However, some sites exhibit unexpected Kmax axes orientations trending perpendicular to the mélange foliation. Analyses of texture and magnetic properties indicate that such unexpected orientations are caused by a predominance of single magnetic domains of magnetite and/or the existence of ankerite and siderite veins in which the long axes of crystals are oriented perpendicular to the foliation in the mélange. As a consequence, the restored shear direction deduced from AMS data improved the credibility of the kinematics of ancient plate motions. Although AMS data provide useful information on shear directions in mélanges, it is essential to examine the magnetic carriers and their magnetic domain structures for accuracy of the analyses.

  18. Modelling the impact of submarine frontal melting and ice mélange on glacier dynamics

    NASA Astrophysics Data System (ADS)

    Krug, J.; Durand, G.; Gagliardini, O.; Weiss, J.

    2015-01-01

    Two mechanisms are generally proposed to explain seasonal variations in the calving front of tidewater glaciers: submarine melting of the calving face and the mechanical back-force applied by the ice mélange. However, the way these processes affect the calving rate and the glacier dynamics remains uncertain. In this study, we used the finite element model Elmer/Ice to simulate the impact of these forcings on more than 200 two dimensional theoretical flowline glacier configurations. The model, which includes calving processes, suggests that frontal melting affects the position of the terminus only slightly (< a few hundred meters) and does not affect the pluriannual glacier mass balance at all. However, the ice mélange has a greater impact on the advance and retreat cycles of the glacier front (more than several 1000 m) and its consequences for the mass balance are not completely negligible, stressing the need for better characterization of forcing properties. We also show that ice mélange forcing against the calving face can mechanically prevent crevasse propagation at sea level and hence prevent calving. Results also revealed different behaviors in grounded and floating glaciers: in the case of a floating extension, the heaviest forcings can disrupt the glacier equilibrium by modifying its buttressing and ice flux at the grounding line.

  19. Lawsonite Blueschists in Recycled Mélange Involved in K-Rich Orogenic Magmatism

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Prelevic, D.; Foley, S. F.; Buhre, S.; Galer, S. J. G.

    2014-12-01

    The origin of K-rich orogenic magmatism in the Alpine-Himalayan belt and its relationship to the large-scale elevations in several massifs of the orogen is controversial, particularly the significance of the widespread presence of a geochemical signal typical for recycled continental crust. Two competing scenarios invoke direct melting of continental crust during deep intercontinental subduction and removal of heavily metasomatised mantle lithosphere by delamination into the convecting mantle. Here we investigate the coupling of high Th/La ratio with crustal isotopic signatures in K-rich orogenic lavas that does not occur in volcanic rocks from other collisional environments to distinguish between these two models. High-pressure experimental results on a phyllite representing upper crustal composition and a detailed mineral and geochemical study of blueschists from Tavşanlı mélange, Turkey, indicate that this geochemical fingerprint originates by melting of subducted mélange. Melting of crust at the top of the subducted continental lithosphere cannot produce observed fingerprint, whereas lawsonites, especially those with terrigenous sediment origin from blueschists with high Th/La can. Lawsonites that grow in various components of a subduction mélange inherit the geochemical characteristics of either oceanic or continental protoliths. It is currently uncertain whether those carrying the high Th/La signature originate by direct melting of continental blocks in the mélange or by the introduction of supercritical fluids from lawsonite blueschist of continental origin that infiltrate oceanic sediment blocks. Either way, the high Th/La is later released into subsequently formed melts. This confirms the supposition that lawsonite is the main progenitor of the high Th/La and Sm/La ratio. However, lawsonite must break down completely to impart this unique feature to subsequent magmas. The source regions of the potassic volcanic rocks consist of blueschist facies mélanges

  20. Cornelia de Lange individuals with new and recurrent SMC1A mutations enhance delineation of mutation repertoire and phenotypic spectrum.

    PubMed

    Gervasini, Cristina; Russo, Silvia; Cereda, Anna; Parenti, Ilaria; Masciadri, Maura; Azzollini, Jacopo; Melis, Daniela; Aravena, Teresa; Doray, Bérénice; Ferrarini, Alessandra; Garavelli, Livia; Selicorni, Angelo; Larizza, Lidia

    2013-11-01

    We report on the clinical and molecular characterization of eight patients, one male and seven females, with clinical diagnosis of Cornelia de Lange syndrome (CdLS), who were found to carry distinct mutations of the SMC1A gene. Five of the eight mutations are novel, with two involving amino acid residues previously described as altered in a different way. The other three have been reported each in a single case. Comparison of pairs of individuals with the same mutation indicates only partial overlap of their clinical phenotypes. The following novel missense mutations, all affecting highly conserved amino acid residues, were found: p.R398G in the N-terminal coiled-coil domain, p.V651M in the C-terminal coiled-coil/hinge junction, p.R693G in the C-terminal coiled-coil, and p.N1166T and p.L1189F in the C-terminal ABC cassette. The latter is localized in the H-loop, and represents the first mutation involving a functional motif of SMC1A protein. The effect of the mutations on SMC1A protein function has been predicted using four bioinformatic tools. All mutations except p.V651M were scored as pathogenic by three or four of the tools. p.V651M was found in the only male individual of our cohort, who presented with the most severe phenotype. This raises the issue of gender effect when addressing mutation-phenotype correlation for genes such as SMC1A, which incompletely escapes X-inactivation. Our clinical and molecular findings expand the total number of characterized SMC1A-mutated patients (from 44 to 52) and the restricted repertoire of SMC1A mutations (from 29 to 34), contributing to the molecular and clinical signature of SMC1A-based CdLS. © 2013 Wiley Periodicals, Inc.

  1. Sedimentary Origins Of The Block-In-Matrix Fabric Of A Mélange Between Coherent Nappes Of A Subduction Complex: Localization Of The Paleosubduction Megathrust Along The Upper Mélange Contact

    NASA Astrophysics Data System (ADS)

    Wakabayashi, J.

    2011-12-01

    The Franciscan subduction complex of California comprises coherent nappes and intervening mélanges. The difference in metamorphic grade and/or accretionary age of adjacent coherent nappes suggests localization of paleosubduction megathrust horizons between them. One of the best examples of a mélange between coherent nappes crops out in an inactive quarry in El Cerrito in the eastern San Francisco Bay area. The upper coherent nappe consists of foliated, jadeite-bearing, blueschist facies metagraywacke, whereas the lower coherent nappe comprises prehnite-pumpellyite facies graywacke with little or no penetrative fabric makes. Detrital zircon geochronology indicates maximum depositional ages of 102 and 100 Ma, respectively, for these units. The foliation or bedding of the graywackes and their contacts strike northwest and dip northeast. C-s fabrics, shear bands, and asymmetric porphyroclasts show a consistent tops-to-the-southwest shear sense in the upper coherent unit, and this fabric developed with syntectonic growth of glaucophane, lawsonite, and jadeite. The intervening mélange has a matrix made up primarily of dark gray shale, with blocks of mostly graywacke, chert, and basalt. The mélange consists of mostly or entirely prehnite-pumpellyite facies material except for the upper 5-10 meters that features metamorphic growth of lawsonite, glaucophane, and jadeite. Thus, the metamorphic contrast between the two nappes, equivalent to at least 10 km in differential burial depth and greater amount of fault displacement, occurs within this narrow zone. The upper half of the mélange (~50 meters of structural thickness) exhibits a pronounced foliation oriented parallel to the bounding contacts. The foliation deflects into shear bands and c-surfaces and this fabric shows a consistent tops-to-the-southwest shear sense. Strain appears to increase structurally upward within the mélange. The structurally lowest part of the mélange displays virtually no strain, with

  2. Unraveling the history of complex zoned garnets from the North Motagua Mélange (Guatemala)

    NASA Astrophysics Data System (ADS)

    Barickman, M. H.; Martin, C.; Flores, K. E.; Harlow, G. E.; Bonnet, G.

    2016-12-01

    The Guatemala Suture Zone (GSZ) is situated in central Guatemala, between the North American and Caribbean plates. Two serpentinite mélanges straddle the Motagua Fault system: the North Motagua Mélange (NMM) and the South Motagua Mélange (SMM). In this study, chemically zoned garnet grains from four eclogite blocks from the NMM were analyzed by EMPA for major elements and LA-ICP-MS for trace elements to unravel the geological history of the eclogites. These eclogites typically consist of euhedral to subhedral garnets, partly retrogressed omphacite grains, and accessory minerals such as phengite and epidote as inclusions in garnet. EBSD was employed to examine apparent garnet inclusions in garnet. The garnet grains in NMM eclogites display complex chemical zonations: all grains roughly show a spessartine-rich core, an almandine-rich core and/or intermediate zone, and a pyrope and grossular-rich rim. Additionally, crystal resorption can be observed between the different zones, and the pyrope-grossular rim can display oscillatory zoning. Finally, grossular-rich zones (crystallographically syntactic) within garnet are present in all studied samples. REE and spider diagrams do not show any significant difference in the patterns of the different zones within the garnet, or indicating that the chemical environment from which each garnet zone grew was broadly the same. The lack of significant variation in LILE content indicates that a fluid influx during garnet growth is unlikely. Consequently, we interpret that garnet grains grew in a largely closed system; however, the presence of the grossular-rich zones, argues for occasional excursions into conditions when either two garnets crystallized or Ca-rich overgrowths that were largely resorbed prior to subsequent continued garnet growth.

  3. Detrital zircon provenance link of the Chinle Formation and the Auld Lang Syne Group in Nevada

    SciTech Connect

    Gehrels, G.E.; Dickinson, W.R. . Dept of Geosciences); Riggs, N. . Dept of Geology)

    1993-04-01

    Previous workers have interpreted the Upper Triassic Auld Lang Syne Group of northwest Nevada as (a) part of a suspect terrane displaced with respect to the craton, or (b) the deltaic terminus of the Chinle depositional system of the Colorado Plateau. U-Pb ages for detrital zircons (air-abraded and analyzed as individual crystals), from sandstones in basal Chinle Fm near Currie and the Osobb Fm (basal Auld Lang Syne Gp) in Dixie Valley, set constraints on the provenance of the two units as follows: (a) Chinle grains (n = 40): 225--235 (n = 2), 505--525 (n = 19), 1,410--1,440 (n = 9), 1,700--1,740 (n = 4); (b) Osobb grains (n = 40): [approximately]235 (n = 1), [approximately]265 (n = 1), 355--415 (n = 3), 510--530 (n = 5), 1,010--1,080 (n = 11), [approximately]1,160 (n = 1), 1,430--1,450 (n = 7), 1,705--1,730 (n = 3). Proterozoic grains were likely shed from basement rocks in the SW US, whereas Triassic grains in both samples and Silurian-Devonian and Permian grains in the Osobb sample may have come from arc terranes to the south (Chinle) or west (Osobb). The Chinle sand is quartzose with only rare chert-quartzite grains, whereas the Osobb sand is subarkosic with chert-argillite and feldspar grains that presumably reflect the admixture of Grenville-age detritus (1,010--1,160 Ma) of uncertain provenance. The most likely source for Cambrian grains (505--530 Ma) is the rift-related igneous province stretching from southern Colorado to SW Oklahoma (Wichita Mtns). Regardless of origin, the unexpected occurrence of Cambrian grains in both Nevada samples supports the suggestion of Lupe and Silberling (1985) that the Auld Lang Syne Gp was deposited as a linked facies equivalent of the Chinle Fm.

  4. Generation of alkaline magmas in subduction zones by melting of mélange diapirs

    NASA Astrophysics Data System (ADS)

    Cruz-Uribe, A. M.; Marschall, H.; Gaetani, G. A.; Le Roux, V.

    2016-12-01

    Alkaline lavas occur globally in subduction-related volcanic arcs. Existing explanations for the occurrence of alkaline lavas in volcanic arcs invoke at least one - and in some cases multiple - `metasomatic' events in addition to the traditional three-component mixing of altered oceanic crust (AOC), sediment melt, and depleted mantle, in order to explain the range of rock types found in a given region. These multi-stage models posit the existence of metasomatized mantle wedge peridotite containing phlogopite or amphibole-enriched veins, which partially melt when fluxed by the addition of materials from the subducted slab. The mélange diapir model is informed by observations and modeling of the subduction side of the arc system, and predicts the generation of alkaline arc magmas by advection of buoyant material from the slab-wedge interface into the mantle wedge below arcs. Here we report results from experiments in which natural mélange materials partially melted at upper mantle conditions were found to produce alkaline magmas compositionally similar to those found in arcs worldwide. The starting material for our experiments is a chlorite-omphacite fels (SY400) from the island of Syros, Greece, that is representative of a hybrid rock containing AOC, sediment, and mantle components. Melting experiments were performed using a piston cylinder apparatus at conditions relevant to the heating-decompression path of mélange diapirs (1000-1300 °C, 1.5-2.5 GPa). The compositions of experimentally produced melts range from 51-61 wt% SiO2, and fall within the trachyte and tephrite-phonolite series (7.5-12.9 wt% Na2O+K2O). Restitic phases in equilibrium with melt include clinopyroxene, garnet (at high P), phlogopite (at high P), amphibole, olivine, rutile, and ilmenite. Partial melts produced in our experiments have trace-element abundance patterns that are typical of alkaline arc lavas, such as enrichment in large ion lithophile elements (Cs, Rb, Ba, Pb, Sr) and alkalis (K

  5. Paracercion ambiguum sp. nov. from Lang Son, Vietnam (Zygoptera: Coenagrionidae).

    PubMed

    Ning, Xin; Kompier, Tom; Yu, Xin; Bu, Wenjun

    2016-07-27

    One new species of Paracercion Weekers and Dumont, 2004 (Paracercion ambiguum Kompier & Yu, 2016, holotype male, Vietnam, Lang Son province, Huu Lien Nature Reserve, 1-XII-2013, deposited in Institute of Entomology, College of Life Sciences of Nankai University, Tianjin, China) is proposed on the basis of molecular and morphological evidence. A COI gene tree is presented for Paracercion species and several morphologically related genera. The species is described and illustrated for both sexes. Diagnostic figures of the genital ligula and caudal appendages are provided.

  6. Controls on accretion of flysch and mélange belts at convergent margins: Evidence from the Chugach Bay thrust and Iceworm mélange, Chugach accretionary wedge, Alaska

    NASA Astrophysics Data System (ADS)

    Kusky, Timothy M.; Bradley, Dwight C.; Haeussler, Peter J.; Karl, Sue

    1997-12-01

    Controls on accretion of flysch and mélange terranes at convergent margins are poorly understood. Southern Alaska's Chugach terrane forms the outboard accretionary margin of the Wrangellia composite terrane, and consists of two major lithotectonic units, including Triassic-Cretaceous mélange of the McHugh Complex and Late Cretaceous flysch of the Valdez Group. The contact between the McHugh Complex and the Valdez Group on the Kenai Peninsula is a tectonic boundary between chaotically deformed melange of argillite, chert, greenstone, and graywacke of the McHugh Complex and a less chaotically deformed mélange of argillite and graywacke of the Valdez Group. We assign the latter to a new, informal unit of formational rank, the Iceworm mélange, and interpret it as a contractional fault zone (Chugach Bay thrust) along which the Valdez Group was emplaced beneath the McHugh Complex. The McHugh Complex had already been deformed and metamorphosed to prehnite-pumpellyite facies prior to formation of the Iceworm mélange. The Chugach Bay thrust formed between 75 and 55 Ma, as shown by Campanian-Maastrichtian depositional ages of the Valdez Group, and fault-related fabrics in the Iceworm mélange that are cut by Paleocene dikes. Motion along the Chugach Bay thrust thus followed Middle to Late Cretaceous collision (circa 90-100 Ma) of the Wrangellia composite terrane with North America. Collision related uplift and erosion of mountains in British Columbia formed a submarine fan on the Farallon plate, and we suggest that attempted subduction of this fan dramatically changed the subduction/accretion style within the Chugach accretionary wedge. We propose a model in which subduction of thinly sedimented plates concentrates shear strains in a narrow zone, generating mélanges like the McHugh in accretionary complexes. Subduction of thickly sedimented plates allows wider distribution of shear strains to accommodate plate convergence, generating a more coherent accretionary style

  7. Of moths and men: Theo Lang and the persistence of Richard Goldschmidt's theory of homosexuality, 1916-1960.

    PubMed

    Dietrich, M R

    2000-01-01

    Using an analogy between moths and men, in 1916, Richard Goldschmidt proposed that homosexuality was a case of genetic intersexuality. As he strove to create a unified theory of sex determination that would encompass animals ranging from moths to men, Goldschmidt's doubts grew concerning the association of homosexuality with intersexuality until, in 1931, he dropped homosexuality from his theory of intersexuality. Despite Goldschmidt's explicit rejection of his theory of homosexuality, Theo Lang, a researcher in the Genealogical-Demographic Department of the Institute for Psychiatric Research in Munich, revived it, maintained Goldschmidt's association with it, and argued on its behalf in publications from 1936 to 1960. Lang's appropriation of Goldschmidt's theory did not depend on his resolution of the difficulties Goldschmidt had found with his own theory. Lang and Goldschmidt, I argue, had fundamentally different scientific and social commitments that allowed one to reject this theory of homosexuality and the other to accept it.

  8. The Casanova Complex of the Northern Apennines: A mélange formed on a distal passive continental margin

    NASA Astrophysics Data System (ADS)

    Naylor, Michaél A.

    1982-01-01

    The Cretaceous-Palaeocene Casanova Complex occurs in two thrust sheets of the eugeosynclinal Ligurids of the Northern Apennines. It is a sedimentary mélange with ophiolitic and quartzose turbidites or limestone-shale olistostrome (submarine debris flows) as matrix. Exotic blocks of ophiolite and granite, serpentinite breccias and lenticular ophiolitic breccias and olistostromes contribute to the mélange character of the complex. Deformational structures include soft-sediment slump folds (indicating a SW-dipping palaeoslope) and boudins, a gradational slumped top to the mélange, small-scale faults in chert blocks and deformation associated with the emplacement of the exotic slide blocks. The blocks were shed as rotational slides from submarine fault scarps and are surrounded by haloes of debris created by submarine weathering. The stacking pattern of the blocks, with the originally stratigraphically highest ophiolite lithologies lowest in the pile of blocks, is explained by a diverticulation model with progressively deeper erosion. Mechanical analysis shows that the blocks were stable when partly exposed resting on a soft sediment substratum. Criteria which distinguish the Casanova Complex from a tectonic mélange, and which may be of value in other mélanges, are discussed. Previous interpretations of the complex as a precursor olistostrome to northeastward nappe emplacement (the Bracco ridge model) are rejected. The mélange is believed to have formed on ocean crust as a result of turbidite and debris flow sedimentation, soft sediment deformation, block faulting, gravity sliding and submarine erosion at the distal edge of a uniformly SW-dipping continental margin.

  9. Levator scapulae and rhomboid transfer for paralysis of trapezius. The Eden-Lange procedure.

    PubMed

    Romero, J; Gerber, C

    2003-11-01

    Spinal accessory nerve palsy leads to painful disability of the shoulder, carrying an uncertain prognosis. We reviewed the long-term outcome in 16 patients who were treated for pain, weakness of active elevation and asymmetry of the shoulder and the neck due to chronic paralysis of the trapezius muscle, as a result of nerve palsy. Of four patients who were treated conservatively, none regained satisfactory function, although two became pain-free. The other 12 patients were treated operatively with transfer of the levator scapulae to the acromion and the rhomboid muscles to the infraspinatus fossa (the Eden-Lange procedure). At a mean follow-up of 32 years, the clinical outcome of the operatively treated patients was excellent in nine, fair in two, and poor in one patient, as determined by the Constant score. Pain was adequately relieved in 11 and overhead function was restored in nine patients. Pre-operative electromyography had been carried out in four patients. In two, who eventually had a poor outcome, a concomitant long thoracic and dorsal scapular nerve lesion had been present. The Eden-Lange procedure gives very satisfactory long-term results for the treatment of isolated paralysis of trapezius. In the presence of an additional serratus anterior palsy or weak rhomboid muscles, the procedure is less successful in restoring shoulder function.

  10. Biomarkers in Tertiary mélange, western Olympic Peninsula, Washington, U.S.A.

    USGS Publications Warehouse

    Kvenvolden, Keith A.; Hostettler, Frances D.; Rapp, John B.; Snavely, Parke D.

    1991-01-01

    Middle Eocene to middle Miocene mélange and broken formations are exposed in the coastal outcrops along the west side of the Olympic Peninsula, Washington. A petroleum geochemical assessment of these geologic units has included the investigation of biomarker compounds. A comparison was made of biomarkers in an oil sample from a middle Miocene reservoir penetrated in the Medina No. 1 well with biomarkers in extracts from two samples of middle Eocene Ozette mélange (one sample having a strong petroliferous odor, and the other sample lacking this characteristic odor). Distribution patterns of n-alkanes, tricyclic terpanes, pentacyclic triterpanes, steranes, and diasteranes are remarkably similar in the oil and rock extracts. Biomarker maturity parameters indicate higher maturity in the oil relative to the extracts. The presence of 17α(H)-23,28-bisnorlupane, 18α(H)- and 18β(H)-oleanane, and de-A-lupane and an odd-carbon-number dominance of the n-alkanes in the oil and extracts seems to tie the hydrocarbons to a common source that has a significant terrigenous component.

  11. Structural analysis and shape-preferred orientation determination of the mélange facies in the Chañaral mélange, Las Tórtolas Formation, Coastal Cordillera, northern Chile

    NASA Astrophysics Data System (ADS)

    Fuentes, Paulina; Díaz-Alvarado, Juan; Fernández, Carlos; Díaz-Azpiroz, Manuel; Rodríguez, Natalia

    2016-04-01

    This study sheds light on the tectonic and structural knowledge of the mélange facies located to the south of Chañaral city, Chile. The Chañaral mélange has been related to an accretionary prism at the western active continental margin of Gondwana. Based on the fossil content, the original turbidite sequence would have been deposited during Devonian to Carboniferous times. The Chañaral mélange is included in the Las Tórtolas Formation, which corresponds to the Paleozoic metasedimentary basement located in the Coastal Range in northern Chile. It consists of a monotonous sequence of more than 90% of interbedded sandstones and shales, with a few limestones, pelagic chert, conglomerates and basic volcanic rocks, metamorphosed to the greenschist facies. In the study area, the Las Tórtolas Formation is divided into two structural domains separated by a major reverse dextral structure, called here the Infieles fault. To the east, the Las Tórtolas Formation is characterized by a brittle-ductile deformation, defined by the original sedimentary contacts in the turbiditic sequence. Besides, thrust faults and associated thrust propagation folds promotes a penetrative axial plane foliation. Mélange facies are located to the west of the Infieles fault. Although lithologies comprising this domain are similar to the rest of the Las Tórtolas Formation, mélange facies (ductile domain) are characterized by the complete disruption of the original architecture of the turbidite succession. The most significant structures in the mélange are the ubiquitous boudinage and pinch and swell structures, asymmetric objects, S-C structures and tight to isoclinal folds. This deformation is partitioned in the Chañaral mélange between linear fabric domains (L), characterized by quartzite blocks with prolate shape in a phyllite matrix with pencil structures, and linear-planar fabric domains (L-S), where quartzite objects show oblate shape and phyllites present a penetrative foliation

  12. High temporal and spatial resolution inverse modeling of mélange rheology at Helheim Glacier, southeast Greenland

    NASA Astrophysics Data System (ADS)

    James, T.; Borstad, C. P.; Drocourt, Y. J. R.; Murray, T.

    2015-12-01

    The calving of icebergs is responsible for a significant proportion of annual mass loss from marine-terminating glaciers and is believed to be a major factor in the rapid demise of paleo-ice sheets. Iceberg calving indirectly influences buttressing against the ice flow by controlling the structure and extent of ice mélange. This mixture of icebergs and seasonal sea ice that forms at the ice-ocean interface of many fast flowing outlet glaciers is believed to have an important influence on the flow of outlet glaciers. However, its physical properties are not well understood and there is disagreement about how to represent it in models. With recent forecasts anticipating that the majority of mass loss from the Greenland Ice Sheet will be dynamic in origin over the next two centuries, improving understanding of the mélange is key. We applied stereo digital photogrammetric methods to a high temporal and spatial resolution time series of time-lapse imagery to generate velocity fields and elevation models of the terminal region and ice mélange of Helheim glacier in Greenland's southeast. For the first time, we use an inverse method implemented in an ice sheet model to determine the spatial pattern of mélange rheology that is consistent with the velocity fields. We explore the variation of the rheology pattern through time to identify areas that support higher stresses and thus provide greater buttressing.

  13. [The modifed Eden-Lange procedure for paralysis of the trapezius muscle].

    PubMed

    Ozalp, Taçkin; Yercan, Hüseyin; Okçu, Güvenir; Erkan, Serkan

    2007-01-01

    Trapezius muscle paralysis results from injury to the spinal accessory nerve. Impairment in the trapezius muscle function may destabilize the muscle resulting in winged scapula. A 25-year-old university student who was active in sports had complaints of shoulder drop and pain on abduction. He had a three-year history of fall resulting in a scapular fracture for which he received conservative treatment. Physical examination showed asymmetry and drop of the right shoulder. Lateral scapular winging was apparent particularly above 90 degrees of abduction. Electromyography revealed isolated paralysis of the trapezius muscle. The patient underwent reconstruction with the modified Eden-Lange procedure. After a two-year follow-up, asymmetry in the shoulder decreased, there was no pain on active abduction, and the patient returned to active sports and was fully satisfied with the outcome.

  14. Context-induced paranormal experiences: support for Houran and Lange's model of haunting phenomena.

    PubMed

    Lange, R; Houran, J

    1997-06-01

    Houran and Lange's psychological model of haunting phenomena predicts that contextual variables alone are sufficient to induce poltergeist-like perceptions. 22 subjects individually visited five areas of a performance theater and were asked to notice the environment. 11 subjects in an informed condition were instructed that the location was haunted, while 11 in the control condition were told that the building was simply under renovation. Subjects' perceptions in both conditions were recorded via Green, et al.'s 1992 experiential questionnaire which contains 10 subscales related to psychological and physiological perceptions. Analysis yielded significantly more intense perceptual experiences on nine of the ten subscales in the informed condition, indicating that demand characteristics alone can stimulate paranormal-type experiences.

  15. Geochemical evidence for mélange melting in global arcs.

    PubMed

    Nielsen, Sune G; Marschall, Horst R

    2017-04-01

    In subduction zones, sediments and hydrothermally altered oceanic crust, which together form part of the subducting slab, contribute to the chemical composition of lavas erupted at the surface to form volcanic arcs. Transport of this material from the slab to the overlying mantle wedge is thought to involve discreet melts and fluids that are released from various portions of the slab. We use a meta-analysis of geochemical data from eight globally representative arcs to show that melts and fluids from individual slab components cannot be responsible for the formation of arc lavas. Instead, the data are compatible with models that first invoke physical mixing of slab components and the mantle wedge, widely referred to as high-pressure mélange, before arc magmas are generated.

  16. Irvin Yalom's Experiment Revisited: Applying Robert Langs's Listening Process to a Psychotherapy Classic.

    PubMed

    Russell, Richard L

    2017-06-01

    In a case now famous for its unconventionality, Irvin Yalom had his financially strapped patient submit written reports of the experience of her therapy sessions rather than pay a monetary fee. He also wrote reports of each session, and the two of them shared royalties from the book, Every Day Gets a Little Closer, eventually produced. The arrangement yielded enough process detail to warrant examination through Robert Langs's method of listening and formulating. From that perspective, it seems Yalom did not understand the encoded messages from his patient in reaction to the frame deviations, which resulted in a deterioration of the communicative field and treatment alliance. Yalom did help his patient to become more appropriately assertive, but her inner fragmentation was untouched.

  17. William W. Lang's contributions to the development of the International Institute of Noise Control Engineering

    NASA Astrophysics Data System (ADS)

    Kihlman, Tor

    2005-09-01

    Bill Lang has been a member of the Board of I-INCE since its first meeting in 1975 in Sendai, Japan. From 1988 to 1999 he served as the President, and to this day remains a very active member of the Board. The INTER-NOISE congress series has been the core activity of I-INCE, and in every case Bill has contributed very actively to secure an excellent congress. He has also taken a number of initiatives both to improve the organization itself and to develop new activities, especially the Technical Study Groups that have prepared consensus reports on important issues such as noise barrier effectiveness and industrial noise hearing conservation policy. At present, he is very active in attempting to develop a global noise control policy.

  18. High-grade metamafic blocks in Franciscan mélanges--olistostromal and/or tectonic?

    NASA Astrophysics Data System (ADS)

    Ernst, W. G.

    2013-12-01

    At ~175 Ma, onset of transpressive plate underflow generated an Andean-type arc along the Californian margin. The east-descending oceanic crust was metamorphosed to eclogite, garnet-blueschist, and amphibolite facies high-pressure (HP) assemblages in an inboard subduction zone at ~165-150 Ma. Except for the fragmentary Red Ant blueschists that crop out in the northern Sierran Foothills, most such metamafic rocks apparently were stored in a low-T environment well into mid- and Late Cretaceous time. Many of the high-grade metamafic rocks returned surfaceward transported as HP tectonic blocks in buoyant Franciscan serpentinite or in subducting, circulating, low-density mud-matrix mélange. However, the rare occurrence of high-grade clasts in relatively feebly recrystallized Franciscan metaconglomerates reflects a sedimentary (including olistostromal) deposition for some HP metamafic blocks. Actinolitic rinds partially encircle many high-grade blocks of either tectonic or olistostromal putative origin. These rinds are only very slightly younger than the subduction-zone metamorphism, suggesting that an early stage of metasomatic exchange took place between HP metabasalt and serpentinized harzburgite along the dynamic oceanic crust-mantle hanging-wall junction, probably while the metamafic rocks were sequestered at moderately shallow mantle depths. For HP metabasaltic rocks to have been added to the Cretaceous Franciscan clastic section as olistoliths, they must first have been carried surfaceward as tectonic blocks immersed in a low-density lithology--probably serpentinite diapirs--then eroded and transported into the trench. Whatever their origin, due to widespread post-depositional convergent-margin shearing, the original natures of many such HP metamafic blocks have been obliterated. In any case, these dense, high-grade rocks of latest Jurassic recrystallization age must have been supplied to the Cretaceous Franciscan accretionary prism by a stage of entrainment in a

  19. A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3

    PubMed Central

    Tonkin, Emma T.; Smith, Melanie; Eichhorn, Piet; Jones, Sandie; Imamwerdi, Burhan; Lindsay, Susan; Jackson, Mike; Wang, Tzu-Jou; Ireland, Maggie; Burn, John; Krantz, Ian D.; Carr, Philippa

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a rare developmental malformation syndrome characterised by mental handicap, growth retardation, distinctive facial features and limb reduction defects. The vast majority of CdLS cases are sporadic. We carried out a high density bacterial artificial chromosome (BAC) microarray comparative genome hybridisation screen but no evidence was found for a consistent pattern of microdeletion/micro-duplication. As an alternative, we focused on identifying chromosomal regions spanning associated translocation breakpoints. We prioritised the distal 3q region because of the occurrence, in a classical CdLS patient, of a de novo balanced translocation with a breakpoint at 3q26.3 and of reports of phenotypic overlap between cases of mild CdLS and individuals trisomic for the 3q26-q27 region. We show that the 3q26.3 breakpoint severs a previously uncharacterised giant gene, NAALADL2, containing at least 32 exons spanning 1.37 Mb. Northern blot analysis identified up to six different transcripts in the 1–10 kb range with strongest expression in kidney and placenta; embryonic expression was largely confined to duodenal and stomach endoderm, mesonephros, metanephros and pancreas. Transcript analysis identified extensive alternative splicing leading to multiple 5′ and 3′ untranslated regions and variable coding sequences. Multiple protein isoforms were defined by different N-terminal regions (with at least four alternative initiating methionine codons), and by differential protein truncation/use of alternative C-terminal sequences attributable to alternative splicing/polyadenylation. Outside the N-terminal regions, the predicted proteins showed significant homology to N-acetylated alpha-linked acidic dipeptidase and transferrin receptors. Mutation screening of NAALADL2 in a panel of CdLS patient DNA samples failed to identify patient-specific mutations. We discuss the possibility that the 3q26.3 translocation could nevertheless contribute to

  20. Age and microfacies of oceanic Upper Triassic radiolarite components from the Middle Jurassic ophiolitic mélange in the Zlatibor Mountains (Inner Dinarides, Serbia) and their provenance

    NASA Astrophysics Data System (ADS)

    Gawlick, Hans-Jürgen; Djerić, Nevenka; Missoni, Sigrid; Bragin, Nikita Yu.; Lein, Richard; Sudar, Milan; Jovanović, Divna

    2017-08-01

    Oceanic radiolarite components from the Middle Jurassic ophiolitic mélange between Trnava and Rožanstvo in the Zlatibor Mountains (Dinaridic Ophiolite Belt) west of the Drina-Ivanjica unit yield Late Triassic radiolarian ages. The microfacies characteristics of the radiolarites show pure ribbon radiolarites without crinoids or thin-shelled bivalves. Beside their age and the preservation of the radiolarians this points to a deposition of the radiolarites on top of the oceanic crust of the Neo-Tethys, which started to open in the Late Anisian. South of the study area the ophiolitic mélange (Gostilje-Ljubiš-Visoka-Radoševo mélange) contains a mixture of blocks of 1) oceanic crust, 2) Middle and Upper Triassic ribbon radiolarites, and 3) open marine limestones from the continental slope. On the basis of this composition we can conclude that the Upper Triassic radiolarite clasts derive either from 1) the younger parts of the sedimentary succession above the oceanic crust near the continental slope or, more convincingly 2) the sedimentary cover of ophiolites in a higher nappe position, because Upper Triassic ribbon radiolarites are only expected in more distal oceanic areas. The ophiolitic mélange in the study area overlies different carbonate blocks of an underlying carbonate-clastic mélange (Sirogojno mélange). We date and describe three localities with different Upper Triassic radiolarite clasts in a mélange, which occurs A) on top of Upper Triassic fore-reef to reefal limestones (Dachstein reef), B) between an Upper Triassic reefal limestone block and a Lower Carnian reef limestone (Wetterstein reef), and C) in fissures of an Upper Triassic lagoonal to back-reef limestone (Dachstein lagoon). The sedimentary features point to a sedimentary and not to a tectonic emplacement of the ophiolitic mélange (= sedimentary mélange) filling the rough topography of the topmost carbonate-clastic mélange below. The block spectrum of the underlying and slightly older

  1. Understanding Mechanisms of Rind Formation in Mélange Zones using Highly Siderophile Elements

    NASA Astrophysics Data System (ADS)

    Gorman, J. K.; Penniston-Dorland, S. C.; Walker, R. J.; Marschall, H. R.

    2012-12-01

    Two mechanisms have previously been proposed for the formation of reaction zones found between mafic and ultramafic rocks in mélange zones. These mechanisms are fluid-assisted metasomatism (transport by fluid flow or by diffusion through an intergranular fluid) and tectonic mixing. We are currently studying the highly siderophile element (HSE) compositions of mafic and ultramafic rocks and reaction zones from several different high P/T metamorphic complexes, including the Catalina Schist (Santa Catalina Island, CA), the Cycladic Complex (Syros, Greece), the Samana Metamorphic Complex (Dominican Republic), and the Franciscan Complex (CA). The mafic rocks in all localities have high 187Os/188Os and low Os, Ir and Ru concentrations, consistent with basaltic protoliths. The more mantle-like rocks (serpentinite, mélange matrix) and the reaction zones have lower 187Os/188Os, and higher Os, Ir and Ru concentrations. Here we report data from traverses across two reaction features: one from the Catalina Schist, the other from the Cycladic complex. The Catalina traverse consists of twelve samples along 30cm between an amphibolite-grade mafic block and its reaction rind (actinolite-chlorite schist) adjacent to ultramafic-rich matrix. The traverse from Syros consists of five samples along 165cm between blueschist-grade metamorphosed volcaniclastic (basaltic to intermediate) tuffs and a >50 m serpentinite lens between which there is a 1-2m thick reaction blackwall zone dominantly consisting of chlorite schist. Samples of the Catalina rind are enriched in whole-rock SiO2, K2O, Rb, Ba, MgO, Cr, Ni, Os, Ir, and Ru relative to samples of the block core, and are depleted in FeO, Al2O3, TiO2, CaO, and Zr. 187Os/188Os ratios are distinctly lower in the rind (0.13 to 0.18) compared to the block (0.43 to 2.23). The Syros blackwall has elevated MgO, CaO, Cr and Ni relative to the non-metasomatised assemblage, while there is depletion of Rb, Ba, and K2O. The HSE concentrations are

  2. Types and Evolutionary Processes of Formation of the Ordovician Taconic Mélanges in the Central and Northern Appalachian Orogenic Belt, Eastern USA

    NASA Astrophysics Data System (ADS)

    Codegone, Giulia; Festa, Andrea; Dilek, Yildirim; Pini, Gian Andrea

    2010-05-01

    We examined in eastern Pennsylvania, New York and Vermont (USA) various types of unmetamorphosed mélanges, which formed at an accretionary wedge-front of the Ordovician Taconic allochthon in the central and northern Appalachian orogenic belt. These mélange occurrences display structural evidence for progressive deformation of a middle-late Ordovician trench-fill succession during the subduction-accretion to collision tectonic episodes of the Taconic Orogeny. Mélanges and broken formations (mélanges s.l.) commonly represent the products of tectonic, sedimentary and diapiric processes during the evolution of accretionary wedges. Geologic mapping and stratigraphic-structural observations in the central and northern Appalachians indicate that different types of mélanges s.l. appear to have developed in different structural positions with respect to the wedge front, and that they show different types of chaotic arrangements and deformation intensities depending on their origin, evolution, and tectonic position. Mass-wasting deposits and/or olistostromes were emplaced at the wedge front as precursory olistostromes of the advancing allochthons, providing exotic material into a flysch succession. These sedimentary mélanges were then overridden by the advancing thrust sheet and were incorporated into the shear zone forming an olistostromal carpet. Shearing led to the juxtaposition and mixing of rocks (in some cases including exotic blocks) of various ages, and subsequently to the formation of boudinage, enucleation of isoclinals folds, and phacoidal microshear cleavages. Broken formations, mainly formed at the base of the wedge front and Taconic thrust fault systems, occur in a continuum ranging from originally coherent stratigraphic successions to variously disrupted strata, and finally to an entirely chaotic block-in-matrix fabric, which lacks a stratigraphic continuity. In-situ accretion-related deformation caused by tectonic loading and related increase of fluid

  3. Discovery of the early Jurassic Gajia mélange in the Bangong-Nujiang suture zone: Southward subduction of the Bangong-Nujiang Ocean?

    NASA Astrophysics Data System (ADS)

    Lai, Wen; Hu, Xiumian; Zhu, Dicheng; An, Wei; Ma, Anlin

    2017-06-01

    lange records a series of geological processes associated with oceanic subduction and continental collision. This paper reports for the first time the presence of Early Jurassic mélange from NW Nagqu in the southern margin of the Bangong-Nujiang suture zone, termed as the Gajia mélange. It shows typically blocks-in-matrix structure with matrix of black shale and siliceous mudstone, and several centimeters to several meters sized blocks of sandstone, silicalite, limestone and basalt. The sandstone blocks consist of homologous sandstone and two types of exotic sandstone, with different modal compositions. The Group 1 of exotic sandstone blocks consists of mainly of feldspar and quartz, whereas the Group 2 is rich in volcanic detritus. The Group 3 of homologous sandstone blocks is rich in feldspar and volcanic detritus with rare occurrence of quartz. U-Pb age data and in situ Hf isotopic compositions of detrital zircons from sandstone blocks are similar to those from the Lhasa terrane, suggesting that the sandstone blocks in the Gajia mélange most probably came from the Lhasa terrane. The YC1σ(2+) age of homologous sandstone blocks is 177 ± 2.4 Ma, suggesting an Early Jurassic depositional age for the sandstones within the Gajia mélange. The Gajia mélange likely records the southward subduction of the Bangong-Nujiang Ocean during the Early Jurassic.

  4. Discovery of the early Jurassic Gajia mélange in the Bangong-Nujiang suture zone: Southward subduction of the Bangong-Nujiang Ocean?

    NASA Astrophysics Data System (ADS)

    Lai, Wen; Hu, Xiumian; Zhu, Dicheng; An, Wei; Ma, Anlin

    2016-10-01

    lange records a series of geological processes associated with oceanic subduction and continental collision. This paper reports for the first time the presence of Early Jurassic mélange from NW Nagqu in the southern margin of the Bangong-Nujiang suture zone, termed as the Gajia mélange. It shows typically blocks-in-matrix structure with matrix of black shale and siliceous mudstone, and several centimeters to several meters sized blocks of sandstone, silicalite, limestone and basalt. The sandstone blocks consist of homologous sandstone and two types of exotic sandstone, with different modal compositions. The Group 1 of exotic sandstone blocks consists of mainly of feldspar and quartz, whereas the Group 2 is rich in volcanic detritus. The Group 3 of homologous sandstone blocks is rich in feldspar and volcanic detritus with rare occurrence of quartz. U-Pb age data and in situ Hf isotopic compositions of detrital zircons from sandstone blocks are similar to those from the Lhasa terrane, suggesting that the sandstone blocks in the Gajia mélange most probably came from the Lhasa terrane. The YC1σ(2+) age of homologous sandstone blocks is 177 ± 2.4 Ma, suggesting an Early Jurassic depositional age for the sandstones within the Gajia mélange. The Gajia mélange likely records the southward subduction of the Bangong-Nujiang Ocean during the Early Jurassic.

  5. Small-scale polygenetic mélanges in the Ligurian accretionary complex, Northern Apennines, Italy, and the role of shale diapirism in superposed mélange evolution in orogenic belts

    NASA Astrophysics Data System (ADS)

    Codegone, Giulia; Festa, Andrea; Dilek, Yildirim; Pini, Gian Andrea

    2012-09-01

    The Argille varicolori (Varicolored scaly clays) of the External Ligurian Units of the Northern Apennines have been widely described as a typical unmetamorphosed broken formation (i.e., a chaotic unit without exotic blocks), produced by offscraping and tectonic imbrication during the evolution of the Ligurian accretionary wedge. Geological mapping and integrated structural and stratigraphic observations show that the Argille varicolori consist of diverse types of small-scale mélanges (non-mappable at a 1:25,000 scale) forming a composite chaotic unit, in which the superposition of tectonic, sedimentary and diapiric processes resulted in the occurrence of polygenetic chaotic bodies at different scales. These mélange units record the evolution of the Ligurian accretionary wedge from subduction to collision and intracontinental deformation. Tectonically Disrupted Body 1 (TDB1) comprises boudinage and pinch-and-swell structures formed by layer-parallel extension/contraction at the wedge front of the Ligurian accretionary complex during the late Cretaceous-middle Eocene. It is interleaved with non-mappable Gravity-driven Chaotic Bodies (GCB) developed during alternating episodes of accretion and removal of material at the wedge front. The late Oligocene-early Miocene out-of-sequence thrusting related to the collisional episodes in the Apennines overprinted the previously formed chaotic bodies and formed a polygenetic tectonic mélange (Tectonically Disrupted Body 2, TDB2). This unit is characterized by a structurally ordered block-in-matrix fabric and by the gradual decrease of stratal disruption away from the regional thrust. Overpressurized fluids concentrated along the shear surfaces, and the scaly cleavage planes facilitated the diapiric upward movement of unconsolidated sediments in the early Miocene. This process produced non-mappable shale dike injections (DDB1) and mappable Diapirically Disrupted Bodies (DDB2), which show an internal zonation of deformation

  6. ModeLang: A New Approach for Experts-Friendly Viral Infections Modeling

    PubMed Central

    Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses. PMID:24454531

  7. Terrestrial lidar measurement of an ongoing calving event on Lange Glacier.

    NASA Astrophysics Data System (ADS)

    Pętlicki, Michał

    2017-04-01

    Increased tourist and scientific marine traffic along the fronts of tidewater glaciers face a security risk due to possible calving-related hazards. A series of serious accidents involving the falling ice block, calving-generated tsunami wave and the ice projectile impacts were reported. Despite the large interest in calving mechanics, still little is known about the impact range of calving events. Three ongoing calving events on Lange Glacier, King George Island, South Shetland Islands were measured with a terrestrial lidar, giving an insight to the mechanics of the calving processes including the subsequent splash of sea water and the range of ice projectiles released from the front. During the acquisition of the point cloud of the ice front, three calving events of different size occurred. The volume of the calved ice, its potential energy and free-fall velocity was computed and compared with the range of the water splash and ice projectiles. Such measurements can be used in future to mitigate the risk of calving-related marine accidents.

  8. Characterization of single spore isolates of Agaricus bisporus (Lange) Imbach using conventional and molecular methods.

    PubMed

    Sharma, Manju; Suman, B C; Gupta, Dharmesh

    2014-10-01

    Strains A-15, S11, S-140, and U3 of Agaricus bisporus (Lange) Imbach, were used as parent strains for raising single spore homokaryotic isolates. Out of total 1,642 single spore isolates, only 36 single spore isolates were homokaryons and exhibited slow mycelial growth rate (≤2.0 mm/day) and appressed colony morphology. All these SSIs failed to produce pinheads in Petri plates even after 65 days of incubation, whereas the strandy slow growing SSIs along with parent strains were able to form the fructification in petriplates after 30 days. Out of 24, six ISSR primers, exhibited scorable bands. In the ISSR fingerprints, single spore isolates, homokaryons, lacked amplification products at multiple loci; they grow slowly and all of them had appressed types of colony morphology. The study revealed losses of ISSR polymorphic patterns in non-fertile homokaryotic single spore isolates compared to the parental control or fertile heterokaryotic single spore isolates.

  9. Scaly fabrics and veins of the Mugi and Makimine mélanges in the Shimanto belt, SW Japan

    NASA Astrophysics Data System (ADS)

    Ramirez, G. E.; Fisher, D. M.; Yamaguchi, A.; Kimura, G.

    2016-12-01

    Two regionally extensive ancient subduction fault zones provide a microstructural record of the plate boundary deformation associated with underthrusting. These rocks exhibit many of the characteristics associated with exposed ancient subduction fault zones worldwide, including: (1) σ1 is near orthogonal to the deformation fabric (2) there are microstructurally pervasive quartz and calcite filled veins concentrated in coarser blocks and along extensional jogs on slip surfaces, (3) evidence for local diffusion of silica sourced from web-like arrays of slip surfaces (i.e., scaly fabrics), and (4) evidence for cycles of cracking and sealing that record cyclic variations in stress. We present new backscatter SEM observations of scaly fabrics from two ancient subduction-related shear zones from the Shimanto Belt in Japan that exemplify these characteristics and represent the full temperature range of the seismogenic zone: 1) the Mugi mélange (lower ( 130-150 °C) and upper ( 170-200 °C) sections) and 2) Makimine mélange (peak temperatures of 340 °C). The Mugi mélange is an underplated duplex consisting of two horses separated by an OOST. The upper section is bounded at the top by a pseudotachylite-bearing paleodécollement. The Makimine mélange was underplated at the downdip limit of the seismogenic zone. The scaly fabrics associated with these shear zones display significantly different microstructural characteristics. A slip surface from along the upper Mugi is characterized by broader ( 20-30 μm), zones of quartz-poor, anastomosing shear zones composed of fine-grained (0.5-2 μm in length) phyllosilicates. The Makimine mélange exhibits thinner (10-20 μm), anastomosing shear zones with coarser (1-4 μm in length) phyllosilicate grains that are more strongly oriented into parallelism with slip surfaces. Quartz veins are pervasively developed in more competent blocks and are oriented at near perpendicular angles to the slip surfaces. Microstructural analyses

  10. Boron Isotopes in Antigorite from the Guatemala Suture Zone Serpentinite Mélanges, Guatemala: Origin of the Serpentinite.

    NASA Astrophysics Data System (ADS)

    Martin, C.; Harlow, G. E.; Marschall, H.

    2014-12-01

    The Guatemala Suture Zone (GSZ) features two serpentinite mélanges straddling the Motagua Fault system. In both North and South Motagua Mélanges (NMM and SMM, respectively), blocks of high-pressure, low-temperature metabasites (e.g., eclogites) are embedded into a serpentinite matrix, together with vein-related rocks (e.g., jadeitites). The origin of serpentinite forming the matrix is still unclear. It is commonly believed to represent either the seafloor / oceanic mantle hydrated by infiltration of seawater or the forearc mantle wedge hydrated by fluid released during subduction. Nowadays, the few data available on serpentinites from Mariana forearc, abyssal peridotite or ophiolitic massifs show positive or slightly negative δ11B (-4.6 to +40‰), in support of the assumption of a shallow origin for the fluid. However, it has been suggested that serpentinites could form much deeper within a subduction channel (~ 30 km depth). In situ boron analyses on antigorite from serpentinites of the GSZ have been carried out by LA-MC-ICPMS and SIMS. Serpentine matrices have low to moderate B concentrations, between 2 and 15µg/g. They display somewhat negative isotopic values, with δ11B of -8.2 ± 2.8 and -11.9 ± 1.2‰ for samples from the NMM, and δ11B of -4.1 ± 3.0 and -11.1 ± 1.8‰ for a sample from the SMM. In addition, this sample contains a late antigorite vein showing a δ11B of -3.0 ± 3.5‰, and some veinlets with scattered values (δ11B ranging from -12.5 ± 0.9 to -6.4 ± 1.4‰). This first suite of measurements carried out directly on serpentinites from serpentinite mélanges displays very negative values, which do not overlap with previously published data. It indicates that the ultramafic precursors of the serpentine from the GSZ Serpentinite Mélanges were not hydrated by seawater, or by fluid released during the early stages of subduction. Rather, these negative values indicate that the fluid responsible for the hydration of ultramafic rocks likely

  11. A novel RAD21 variant associated with intrafamilial phenotypic variation in Cornelia de Lange syndrome - review of the literature.

    PubMed

    Boyle, M I; Jespersgaard, C; Nazaryan, L; Bisgaard, A-M; Tümer, Z

    2017-04-01

    In a patient with CdLS (IV.16) we identifed a novel single basepair deletion (c.704delG) in RAD21, which encodes a cohesin pathway protein. The variant is predicted to result in a premature stop codon [p.(Ser235Ilefs*19)] and hereby would have a deleterious effect. RAD21 variants have previously been described only in five cases with cohesinopathies (b). Notably, the deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study (a). The index patient can be classified as mild CdLS, but the other family members do not fulfill the diagnostic criteria of CdLS. This study together with previous reports suggests incomplete penetrance associated with RAD21 variants and these individuals may therefore be underdiagnosed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Genetic and clinical advances in congenital long QT syndrome.

    PubMed

    Mizusawa, Yuka; Horie, Minoru; Wilde, Arthur A M

    2014-01-01

    Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval on the 12-lead ECG, torsades de pointes and a higher chance of sudden cardiac death. LQTS segregates in a Mendelian fashion, which includes Romano-Ward syndrome with an autosomal dominant pattern as well as a rare autosomal recessive pattern (Jervell and Lange-Nielsen syndrome). Since 1957 when Jervell and Lange-Nielsen reported the first familial LQTS with congenital deafness, progress in understanding the genetic and electrophysiological mechanisms of LQTS has tremendously improved diagnostic methods and treatments. In the meantime, it has become evident that LQTS may not always be explained by a single gene mutation, but seems to follow a more complex genetic model intertwined with genetic common polymorphisms that have a mild to moderate effect on disease expression. In this review, we summarize the characteristics of LQTS (mainly LQT1-3) and briefly describe the most recent advances in LQTS clinical diagnostics as well as genetics.

  13. Interpretation of tracer tests performed in fractured rock of the Lange Bramke basin, Germany

    NASA Astrophysics Data System (ADS)

    Maloszewski, Piotr; Herrmann, Andreas; Zuber, Andrzej

    Two multitracer tests performed in one of the major cross-fault zones of the Lange Bramke basin (Harz Mountains, Germany) confirm the dominant role of the fault zone in groundwater flow and solute transport. Tracers having different coefficients of molecular diffusion (deuterium, bromide, uranine, and eosine) yielded breakthrough curves that can only be explained by a model that couples the advective-dispersive transport in the fractures with the molecular diffusion exchange in the matrix. For the scale of the tests (maximum distance of 225m), an approximation was used in which the influence of adjacent fractures is neglected. That model yielded nearly the same rock and transport parameters for each tracer, which means that the single-fracture approximation is acceptable and that matrix diffusion plays an important role. The hydraulic conductivity of the fault zone obtained from the tracer tests is about 1.5×10-2m/s, whereas the regional hydraulic conductivity of the fractured rock mass is about 3×10-7m/s, as estimated from the tritium age and the matrix porosity of about 2%. These values show that the hydraulic conductivity along the fault is several orders of magnitude larger than that of the remaining fractured part of the aquifer, which confirms the dominant role of the fault zones as collectors of water and conductors of fast flow. Résumé Deux multitraçages ont été réalisés dans l'une des zones principales de failles du bassin de Lange Bramke (massif du Harz, Allemagne); les résultats confirment le rôle prédominant de la zone de failles pour l'écoulement souterrain et le transport de soluté. Les traceurs, possédant des coefficients de diffusion différents (deutérium, bromure, uranine et éosine), ont fourni des courbes de restitution qui ne peuvent être expliquées que par un modèle qui associe un transport advectif-dispersif dans les fractures à un échange par diffusion moléculaire dans la matrice. A l'échelle des expériences (distance

  14. Geochemistry and geochronology of HP mélanges from Tinos and Andros, cycladic blueschist belt, Greece

    NASA Astrophysics Data System (ADS)

    Bulle, Florian; Bröcker, Michael; Gärtner, Claudia; Keasling, Alan

    2010-06-01

    U-Pb zircon geochronology, Sr-Nd isotope and bulk-rock geochemistry have been applied to meta-igneous and meta-sedimentary rocks from high-pressure metamorphic mélanges exposed on the Cycladic islands of Tinos, Syros and Andros. Ion microprobe (SHRIMP) U-Pb zircon dating of 7 samples representing meta-igneous blocks (Tinos), a blackwall zone (Tinos) and chlorite-talc schists from block-matrix contacts (Syros and Tinos) yielded Cretaceous ages of c. 80 Ma. Many of the criteria commonly used to distinguish between magmatic or metamorphic zircon genesis (internal structure, Th/U ratio, REE characteristics, Ti-in zircon thermometry, enclosed mineral phases) do not provide unambiguous constraints for the mode of formation. However, a magmatic origin for Cretaceous zircon of meta-gabbros and eclogites is considered likely. Supporting evidence for a previously suggested metamorphic origin for c. 80 Ma zircon in eclogite has not been found. Zircon of the same age occurring in chlorite-talc schists is presumably related to non-magmatic processes. Well-defined Cretaceous age groups clustering at c. 79 Ma also occur in the detrital zircon populations of 2 quartz mica schists representing the mélange matrix on Tinos, and suggest a much later time for sediment accumulation than previously assumed. The importance of c. 57 Ma zircon ages remains unclear, but may record either HP metamorphic processes or a post-57 Ma depositional age. The youngest age group in a third quartz mica schist from Tinos, collected outside the main mélange occurrences, clusters at c. 226-238 Ma. In all clastic metasediments from Tinos, most data points plot along the concordia between c. 300 and 900 Ma; single data points indicate concordant ages of c. 2.5 Ga, 2.3 Ga and 1 Ga, respectively. The youngest 206Pb/ 238U age group that has been recognized in a felsic paragneiss from Andros indicates an age of 163.1 ± 3.9 Ma, and mostly represents overgrowths around zircon with ages in the range from ˜ 272

  15. Tectonic mélanges and the exhumation of HP ophiolites: a case-study from the Ligurian Alps

    NASA Astrophysics Data System (ADS)

    Federico, Laura; Crispini, Laura; Scambelluri, Marco; Capponi, Giovanni; Malatesta, Cristina

    2010-05-01

    langes form in a variety of geodynamic settings and can be related to either sedimentary, tectonic or diapiric processes, or a combination of them. We studied in detail a 100 m-scale tectonic mélange formed in the context of the alpine subduction/collision and we tested if the local-scale pattern could be applicable at larger scale in the Ligurian Western Alps. The studied mélange crops out inside metamorphic serpentinites belonging to the high-pressure (HP), meta-ophiolitic Voltri Massif (southern end of the Western Alps). It is made up of a foliated chlorite-actinolite greenschist matrix enclosing 10m-scale lenses of metabasites and metasediments. These blocks appear to be exotic because similar rocks do not outcrop in the surrounding HP-units. The matrix records three sets of superposed folds from blueschist to greenschist-facies conditions. The metabasite lenses preserve internal HP schistosities forming high angles with the greenschist matrix foliation. The lenses equilibrated at different peak metamorphic conditions (ranging from eclogite- to blueschist-facies). The matrix is widely retrogressed in greenschist facies, but it contains rare relics of Na-amphibole. Individual lenses display different segments of typical subduction PT paths which apparently converge in the blueschist facies. Moreover, geochronological data for the different HP blocks show that two undistinguishable blueschist samples display distinct peak ages of 43 and 40 Ma. One blueschist age is contemporaneous with the eclogitic equilibration of another block (43.2 ± 0.5 Ma) (Federico et al., 2007). The described structural, metamorphic and geochronological features suggest that this mélange formed at depth in a subduction channel and was active at least from blueschist- to greenschist-facies conditions, but possibly also at higher pressures. The subduction channel formed between the overriding and the subducting plates, as a consequence of progressive hydration of the mantle wedge by

  16. Équilibre chimique dans des mélanges gazeux en déséquilibre thermique

    NASA Astrophysics Data System (ADS)

    Cayet, S.; Dudeck, M.

    1996-03-01

    A new mathematical development has allowed the White and Dantzig method of calculating equilibrium concentrations to be applied to gas mixtures in thermal disequilibrium. The general principle of the method remains the search for the minimum free enthalpy of the mixture, but the calculation conditions have changed since the temperature is no longer uniform: it is therefore possible to deal with cases of mixtures of plasmas where the electrons are generally hotter than the heavier species. The mathematical development and the development of a micro-computer algorithm are described. Un nouveau développement mathématique a permis d'adapter au cas d'un mélange gazeux en déséquilibre thermique la méthode de calcul des concentrations à l'équilibre de White et Dantzig. Le principe général de la méthode reste la recherche du minimum de l'enthalpie libre du mélange, mais les conditions du calcul ont changé puisque la température n'est plus unique: il sera donc possible de traiter le cas des mélanges plasmas où les électrons sont en général plus énergétiques que les espèces lourdes. Le développement mathématique et la mise en oeuvre de l'algorithme sur micro-ordinateur sont décrits.

  17. Kinematic analysis of mélange fabrics: examples and applications from the McHugh Complex, Kenai Peninsula, Alaska

    NASA Astrophysics Data System (ADS)

    Kusky, Timothy M.; Bradley, Dwight C.

    1999-12-01

    Permian to Cretaceous mélange of the McHugh Complex on the Kenai Peninsula, south-central Alaska includes blocks and belts of graywacke, argillite, limestone, chert, basalt, gabbro, and ultramafic rocks, intruded by a variety of igneous rocks. An oceanic plate stratigraphy is repeated hundreds of times across the map area, but most structures at the outcrop scale extend lithological layering. Strong rheological units occur as blocks within a matrix that flowed around the competent blocks during deformation, forming broken formation and mélange. Deformation was noncoaxial, and disruption of primary layering was a consequence of general strain driven by plate convergence in a relatively narrow zone between the overriding accretionary wedge and the downgoing, generally thinly sedimented oceanic plate. Soft-sediment deformation processes do not appear to have played a major role in the formation of the mélange. A model for deformation at the toe of the wedge is proposed in which layers oriented at low angles to σ1 are contracted in both the brittle and ductile regimes, layers at 30-45° to σ1 are extended in the brittle regime and contracted in the ductile regime, and layers at angles greater than 45° to σ1 are extended in both the brittle and ductile regimes. Imbrication in thrust duplexes occurs at deeper levels within the wedge. Many structures within mélange of the McHugh Complex are asymmetric and record kinematic information consistent with the inferred structural setting in an accretionary wedge. A displacement field for the McHugh Complex on the lower Kenai Peninsula includes three belts: an inboard belt of Late Triassic rocks records west-to-east-directed slip of hanging walls, a central belt of predominantly Early Jurassic rocks records north-south directed displacements, and Early Cretaceous rocks in an outboard belt preserve southwest-northeast directed slip vectors. Although precise ages of accretion are unknown, slip directions are compatible with

  18. [Syndromes 2. Pfeiffer syndrome].

    PubMed

    Freihofer, H P

    1998-07-01

    Acrocephalosyndactylias are syndromes characterized by abnormalities of the head (craniosynostosis), the face (hypertelorism, retromaxillism), hands and feet (cutaneous or bony syndactyly). Inheritance is autosomal dominant, but spontaneous cases are described also. The group is divided into several syndromes with varying penetrance and expressivity. As an example of an acrocephalosyndactylia is the Pfeiffer syndrome presented.

  19. Formation of diamondiferous kyanite-eclogite in a subduction mélange

    NASA Astrophysics Data System (ADS)

    Aulbach, S.; Gerdes, A.; Viljoen, K. S.

    2016-04-01

    interaction reconciles evidence for both low- and high-pressure igneous processes in some aluminous eclogites. We suggest that a subduction mélange is a favourable setting for the transfer of a sediment-derived signature into oceanic crust, leading to formation of diamondiferous kyanite-eclogites from bimineralic eclogites. Diapirism, fluxed by the presence of partial melt, may have facilitated dispersal of the eclogites in the lithosphere column, consistent with their widely varying equilibration pressures ranging from ∼5 to 8 GPa.

  20. Provenance of the Indus-Yarlung Suture Mélange and the Location of the India-Asia Suture, Southern Tibet

    NASA Astrophysics Data System (ADS)

    Metcalf, K.; Kapp, P. A.; Orme, D. A.; Laskowski, A. K.

    2013-12-01

    The Indus-Yarlung Suture Zone (IYSZ) is the boundary between rocks of Indian and Asian affinity. From north to south in southern Tibet, it exposes the preserved Asian forearc, ophiolitic rocks, tectonic mélanges, and Tethyan Himalayan strata of Indian affinity. The mélange has long been considered the accretionary prism corresponding to the ophiolite to the north which obducted onto the Indian margin prior to India-Asia collision. An outstanding issue is whether the ophiolitic rocks and mélanges were (1) obducted onto the northern margin of India or (2) associated with the Cordilleran-style southern margin of Asia, prior to India - Asia collision. Resolving this issue is fundamental to understanding the precollisional tectonic framework of the Neo-Tethyan realm, interpreting the timing of initial continental collision from detrital records, and locating the suture. We conducted geologic mapping and U/Pb detrital zircon provenance studies of the blocks and matrix of the mélanges and of Tethyan Himalayan units to the south at two localities: near Lhatse, which is ~140 km north of Mt. Everest and near Lopu Kangri, ~300 km along strike to the west. Near Lhatse the mélange is composed of a mudstone matrix with blocks of basalt, chert, mudstone, metabasite, limestone, and sandstone. The majority of the blocks are deep-water facies or consistent with oceanic crust, supporting the interpretation that the mélange is an accretionary complex formed by oceanic subduction. A south-dipping fault ~9 km north of Lhatse separates the mélange to the north from a continuous sequence of sandstone, shale, and minor limestone to the south. Previous work along strike suggests that this sequence, which has been previously identified as Tethyan affinity, contains Asian affinity detrital zircon populations. Near Lopu Kangri, the mélange is similar to that exposed in Lhatse. Over a distance of ~10 km to the southwest, blocks gradually increase in size to encompass ~2 km x ~10 km

  1. Fluid-metapelite interaction in an ultramafic mélange: implications for mass transfer along the slab-mantle interface in subduction zones

    NASA Astrophysics Data System (ADS)

    Mori, Yasushi; Shigeno, Miki; Nishiyama, Tadao

    2014-12-01

    The slab-mantle interface in subduction zones is a site of tectonic mixing of crustal and mantle rocks. It is the interface for fluid flow of slab-derived components into the mantle wedge. To assess the fluid-rock interaction along the slab-mantle interface, we studied the bleaching of pelitic schist in an ultramafic mélange. The Nishisonogi metamorphic rocks in Kyushu, Japan, comprise ultramafic mélanges intercalated with epidote-blueschist facies schists. The ultramafic mélange consists of tectonic blocks of various lithologies and a matrix of chlorite-actinolite schist and serpentinite. Along the contact with the mélange matrix, pelitic schist blocks are bleached mainly due to the modal increase of albite and the consumption of carbonaceous material. The bleaching is probably attributed to infiltration of Na-rich external fluid from the mélange matrix. Mass balance analysis indicates losses of C, Rb, K2O, Ba, Pb, and SiO2 from the bleached pelitic schist, although Al2O3, TiO2, Sc, Y, Zr, Nb, La, Ce, and Nd remain immobile. This suggests fractionation of large-ion lithophile elements (LILE) and Pb from the high-field-strength elements and rare earth elements during the bleaching. If this ultramafic mélange is analogous to the slab-mantle interface, similar infiltration metasomatism will promote liberation of C, Si, LILE, and Pb from subducting metapelites and enhance metasomatism of the mantle wedge.

  2. Bill Lang's contributions to acoustics at the International Business Machines Corp. (IBM) and to IBM in general

    NASA Astrophysics Data System (ADS)

    Nobile, Matthew A.; Chu, Richard C.

    2005-09-01

    Although Bill Lang's accomplishments and key roles in national and international standards and in the formation of INCE are widely recognized, sometimes it has to be remembered that for nearly 35 years he also had a ``day job'' at the IBM Corporation. His achievements at IBM were no less significant and enduring than those in external standards and professional societies. This paper will highlight some of the accomplishments and activities of Bill Lang as an IBM noise control engineer, the creator of the IBM Acoustics Lab in Poughkeepsie, the founder of the global Acoustics program at IBM, and his many other IBM leadership roles. Bill was also a long-serving IBM manager, with the full set of personnel issues to deal with, so his people-management skills were often called into play. Bill ended his long and fruitful IBM career at a high point. In 1988, he took an original idea of his to the top of IBM executive management, which led directly to the formation of the IBM Academy of Technology, today the preeminent body of IBM top technical leaders from around the world.

  3. In Vitro Antioxidant Activities and in Vivo Anti-Hypoxic Activity of the Edible Mushroom Agaricus bisporus (Lange) Sing. Chaidam.

    PubMed

    Li, Hong-Ji; Chen, Hai-Yan; Fan, Lin-Lin; Jiao, Zhi-Hua; Chen, Qi-He; Jiao, Ying-Chun

    2015-09-25

    With the rising awareness of a healthy lifestyle, natural functional foods have gained much interest as promising alternatives to synthetic functional drugs. Recently, wild Agaricus bisporus (Lange) Sing. Chaidam has been found and artificially cultivated for its thick fresh body and excellent taste, with its antioxidant and anti-hypoxic abilities unknown. In this work, the antioxidant potential of its methanolic, 55% ethanolic, aqueous extracts and crude polysaccharide was evaluated in different systems. The results showed that polysaccharide was the most effective in scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, metal chelating activity and reducing power, with EC50 values of 0.02, 2.79, 1.29, and 1.82 mg/mL, respectively. Therefore, we further studied the anti-hypoxic activity of crude polysaccharide. The results turned out that polysaccharide (300 mg/kg) prolonged the survival time, decreased the blood urea nitrogen and lactic acid content as well as increased the liver glycogen significantly, compared with the blank control and the commercialized product Hongjingtian (p < 0.05). With such excellent activities, we purified the polysaccharide and analyzed its molecular weight (120 kDa) as well as monosaccharide components (glucose, fructose and mannose). This study indicated that wild Agaricus bisporus (Lange) Sing. Chaidam had strong potential to be exploited as an effective natural functional food to relieve oxidative and hypoxia stresses.

  4. Disorders of Transcriptional Regulation: An Emerging Category of Multiple Malformation Syndromes

    PubMed Central

    Izumi, Kosuke

    2016-01-01

    Some genetic disorders caused by mutations in genes encoding components of the transcriptional machinery as well as proteins involved in epigenetic modification of the genome share many overlapping features, such as facial dysmorphisms, growth problems and developmental delay/intellectual disability. As a basis for some shared phenotypic characteristics in these syndromes, a similar transcriptome disturbance, characterized by global transcriptional dysregulation, is believed to play a major role. In this review article, a general overview of gene transcription is provided, and the current knowledge of the mechanisms underlying some disorders of transcriptional regulation, such as Rubinstein- Taybi, Coffin-Siris, Cornelia de Lange, and CHOPS syndromes, are discussed. PMID:27867341

  5. Structure and Tectonics of Subophiolitic Mélanges in the Western Hellenides (Greece) and Implications for Ophiolitic Root Zones in the Balkans

    NASA Astrophysics Data System (ADS)

    Ghikas, Constandina; Dilek, Yildirim; Rassios, Anne E.

    2010-05-01

    The Jurassic Vourinos ophiolite is part of the Western Hellenide ophiolite belt in Greece and rests tectonically on the Pelagonian ribbon continent. The Vourinos and coeval Pindos ophiolite to the west display suprasubduction-zone geochemical affinities, and represent remnants of oceanic lithosphere formed in a rifted incipient arc-forearc setting within the Pindos Basin. In structurally descending order, and from west to east, the subophiolitic mélange beneath the Vourinos ophiolite contains the Agios Nikolaos Formation (ANF) and a rift assemblage, both of which display ENE-vergent thrust faults, shear zones, and folds. The ANF comprises schistose mudstone with pebbles, cobbles, and boulders of arenite and wacke derived from the crystalline basement of Pelagonia. Imbricated along ENE-directed thrust faults and metamorphosed up to lower amphibolite facies, the ANF represents continental rise deposits of the rifted Pelagonian margin. The rift assemblage includes blocks of basaltic lavas, ribbon chert, micritic cherty limestone, metagabbro, dolerite dikes, and serpentinite breccia that are commonly in thrust contact with each other and are tectonically imbricated with the Pelagonian carbonates; however, primary intrusive and depositional contacts are locally well preserved. Gabbro and dolerite dikes are locally intrusive into the recrystallized carbonates and metapelitic rocks of Pelagonia. Lavas display mid-ocean ridge basalt-within plate basalt affinities and represent Upper Triassic rift units that erupted during the separation of Pelagonia from Apulia. Gabbro, dolerite, and serpentinite breccia are the products of a magmatic rifting episode prior to the onset of seafloor spreading in the Pindos Basin. The Vourinos subophiolitic mélange thus consists of passive margin and rift assemblages that were tectonically overridden by the Vourinos ophiolite in the middle Jurassic. Its internal structure and evolutionary history represent a tectonic mélange character of

  6. Sedimentary environment of a halite-mudrock mélange (Haselgebirge Formation, Eastern Alps)

    NASA Astrophysics Data System (ADS)

    Leitner, Christoph; Köster, Mathias H.; Neubauer, Franz

    2015-04-01

    During Variscan orogeny in Carboniferous times, Gondwana and Europe collided to form Pangea (Stampfli et al., 2013). The succeeding Permian was a time of continental consolidation and erosion of the uplifted Vaiscan mountain belt but also its destruction by rifting processes forming the Tethys Sea (in its initial definition). During late Permian (c. 255-250 Ma), when the later Eastern Alps were located around north of the equator, evaporites of the Haselgebirge Formation (now exposed in Northern Calcareous Alps) were deposited. The location of the deposits was at around 10° north of the equator, which would be at the transition from a tropical climate to a moderate to semi-aride climate nowadays (Blakey, 2008), but on the other side the average temperature can be assumed higher than today (Berner, 1998). In salt mines, the Haselgebirge Fm. consists of a two-component tectonite of c. 50 % halite and 50 % sedimentary clastic and other evaporite rocks (Schauberger, 1986; Spötl 1998). Most of the clastic rocks are mud- to siltstones ("mudrock"). Its present appearance as a tectonic mélange is a result of the superimposed stages of Alpine orogenic events during Jurassic, Cretaceous and Cenocoic times. During the present study, we investigated the sedimentary/ diagenetic development of the evaporite rocks by field work in underground salt mines (Hallstatt, Berchtesgaden, Bad Dürrnberg, Altaussee), thin section analysis, SEM, RDX and EMPA. Mudrock needs a quiet or non-turbulent environment to settle down. Higher water energy leads to non-horizontal structures like ripples, re-sedimentation of clasts and a larger grain size. Therefore, water depth was in general deeper than 5 m, but the question remains unanswered how deep the basin could become in its deepest parts. Massive anhydrite rock precipitated from sea water (layered, black), while nodular/mosaic anhydrite (red) crystallized within the sediment (earlier or coevally). The transition gypsum  anhydrite

  7. Jurassic-Paleogene intra-oceanic magmatic evolution of the Ankara Mélange, North-Central Anatolia, Turkey

    NASA Astrophysics Data System (ADS)

    Sarifakioglu, E.; Dilek, Y.; Sevin, M.

    2013-11-01

    Oceanic rocks in the Ankara Mélange along the Izmir-Ankara-Erzincan suture zone (IAESZ) in North-Central Anatolia include locally coherent ophiolite complexes (~179 Ma and ~80 Ma), seamount or oceanic plateau volcanic units with pelagic and reefal limestones (96.6 ± 1.8 Ma), metamorphic rocks with ages of 187.4 ± 3.7 Ma, 158.4 ± 4.2 Ma, and 83.5 ± 1.2 Ma, and subalkaline to alkaline volcanic and plutonic rocks of an island arc origin (~67-63 Ma). All but the arc rocks occur in a shaly-graywacke and/or serpentinite matrix, and are deformed by south-vergent thrust faults and folds that developed in the Middle to Late Eocene due to continental collisions in the region. Ophiolitic volcanic rocks have mid-ocean ridge (MORB) and island arc tholeiite (IAT) affinities showing moderate to significant LILE enrichment and depletion in Nb, Hf, Ti, Y and Yb, which indicate the influence of subduction-derived fluids in their melt evolution. Seamount/oceanic plateau basalts show ocean island basalt (OIB) affinities. The arc-related volcanic rocks, lamprophyric dikes and syeno-dioritic plutons exhibit high-K shoshonitic to medium-to high-K calc-alkaline compositions with strong enrichment in LILE, REE and Pb, and initial ϵNd values between +1.3 and +1.7. Subalkaline arc volcanic units occur in the northern part of the mélange, whereas the younger alkaline volcanic rocks and intrusions (lamprophyre dikes and syeno-dioritic plutons) in the southern part. The Early to Late Jurassic and Late Cretaceous epidote-actinolite, epidote-chlorite and epidote-glaucophane schists represent the metamorphic units formed in a subduction channel in the Northern Neotethys. The Middle to Upper Triassic neritic limestones spatially associated with the seamount volcanic rocks indicate that the Northern Neotethys was an open ocean with its MORB-type oceanic lithosphere by the Early Triassic. The Latest Cretaceous-Early Paleocene island arc volcanic, dike and plutonic rocks with

  8. Jurassic-Paleogene intraoceanic magmatic evolution of the Ankara Mélange, north-central Anatolia, Turkey

    NASA Astrophysics Data System (ADS)

    Sarifakioglu, E.; Dilek, Y.; Sevin, M.

    2014-02-01

    Oceanic rocks in the Ankara Mélange along the Izmir-Ankara-Erzincan suture zone (IAESZ) in north-central Anatolia include locally coherent ophiolite complexes (∼ 179 Ma and ∼ 80 Ma), seamount or oceanic plateau volcanic units with pelagic and reefal limestones (96.6 ± 1.8 Ma), metamorphic rocks with ages of 256.9 ± 8.0 Ma, 187.4 ± 3.7 Ma, 158.4 ± 4.2 Ma, and 83.5 ± 1.2 Ma indicating northern Tethys during the late Paleozoic through Cretaceous, and subalkaline to alkaline volcanic and plutonic rocks of an island arc origin (∼ 67-63 Ma). All but the arc rocks occur in a shale-graywacke and/or serpentinite matrix, and are deformed by south-vergent thrust faults and folds that developed in the middle to late Eocene due to continental collisions in the region. Ophiolitic volcanic rocks have mid-ocean ridge (MORB) and island arc tholeiite (IAT) affinities showing moderate to significant large ion lithophile elements (LILE) enrichment and depletion in Nb, Hf, Ti, Y and Yb, which indicate the influence of subduction-derived fluids in their melt evolution. Seamount/oceanic plateau basalts show ocean island basalt (OIB) affinities. The arc-related volcanic rocks, lamprophyric dikes and syenodioritic plutons exhibit high-K shoshonitic to medium- to high-K calc-alkaline compositions with strong enrichment in LILE, rare earth elements (REE) and Pb, and initial ɛNd values between +1.3 and +1.7. Subalkaline arc volcanic units occur in the northern part of the mélange, whereas the younger alkaline volcanic rocks and intrusions (lamprophyre dikes and syenodioritic plutons) in the southern part. The late Permian, Early to Late Jurassic, and Late Cretaceous amphibole-epidote schist, epidote-actinolite, epidote-chlorite and epidote-glaucophane schists represent the metamorphic units formed in a subduction channel in the northern Neotethys. The Middle to Upper Triassic neritic limestones spatially associated with the seamount volcanic rocks indicate that the northern

  9. Unraveling the polymetamorphic history of garnet-bearing metabasites: Insights from the North Motagua Mélange (Guatemala Suture Zone)

    NASA Astrophysics Data System (ADS)

    Bonnet, G.; Flores, K. E.; Martin, C.; Harlow, G. E.

    2014-12-01

    The Guatemala Suture Zone is the fault-bound region in central Guatemala that contains the present North American-Caribbean plate boundary. This major composite geotectonic unit contains a variety of ophiolites, serpentinite mélanges, and metavolcano-sedimentary sequences along with high-grade schists, gneisses, low-grade metasediments and metagranites thrusted north and south of the active Motagua fault system (MFS). The North Motagua Mélange (NMM) outcrops north of the MFS and testifies the emplacement of exhumed subduction assemblages along a collisional tectonic setting. The NMM is composed of a serpentinite-matrix mélange that contains blocks of metabasites (subgreenschist facies metabasalt, grt-blueschist, eclogite, grt-amphibolite), vein-related rocks (jadeitite, omphacitite, albitite, mica-rock), and metatrondhjemites. Our new detailed petrographic and thermobarometric study on the garnet-bearing metabasites reveals a complex polymetamorphic history with multiple tectonic events. Eclogites show a classical clockwise PT path composed of (a) prograde blueschist/eclogite facies within garnet cores, (b) eclogite facies metamorphic peak at ~1.7 GPa and 620°C, (c) post-peak blueschist facies, (d) amphibolite facies overprint, and (e) late stage greenschist facies. Two types of garnet amphibolite blocks can be found, the first consist of (a) a relict eclogite facies peak at ~1.3 GPa and 550°C only preserved within anhedral garnet cores, and (b) surrounded by a post-peak amphibolite facies. In contrast, the second type displays a prograde amphibolite facies at 0.6-1.1 GPa and 400-650°C. The eclogites metamorphic peak suggests formation in a normal subduction zone at ~60 km depth, a subsequent exhumation to the middle section of the subduction channel (~35 km), and a later metamorphic reworking at lower P and higher T before its final exhumation. The first type of garnet amphibolite shows a similar trajectory as the eclogites but at warmer conditions. In

  10. The Relationship between American Counseling Association Members' Professional Affiliations and Advocacy Attitudes and Actions as Defined by the Lange Profession Advocacy Scale

    ERIC Educational Resources Information Center

    Lange, Amber

    2009-01-01

    A sample of American Counseling Association (ACA) members and the entire population of the ACA Legislative Institute attendants was investigated to determine if any variables were contributing to strong scores on the Lange Profession Advocacy Scale (LPAS), a Rasch analyzed instrument. A total of 563 cases had a valid measure score and were…

  11. Structural rejuvenation of the eastern Arabian Shield during continental collision: 40Ar/ 39Ar evidence from the Ar Ridayniyah ophiolitic mélange

    NASA Astrophysics Data System (ADS)

    Al-Saleh, A. M.; Boyle, A. P.

    2001-07-01

    The Ar Ridayniyah ophiolitic mélange is one of a number of such complexes found within or at the peripheries of the Neoproterozoic Al-Amar Suture of the eastern Arabian Shield. This suture is sandwiched between the Ar Rayn island-arc terrane on the east and the much larger Afif continental block to the west, and is thought to represent the site of a 695—680 Ma back-arc basin that separated the two terranes. A thick and monotonous unit of metagraywacke (Abt Schist) underlies most of the suture along with scattered outcrops of metavolcanics and ophiolitic mélange. One of these bodies is the Ar Ridayniyah mélange, which occurs as a longitudinal belt of sheared ultramafic schists enclosing abundant blocks of oceanic serpentinites, as well as subordinate gabbros and basalts. The western boundary of this mélange is defined by the Ar Ridayniyah thrust fault. The 610—600 Ma ages obtained from the metagabbros of this complex are considered to record the reactivation of the Ar Ridayniyah Fault during continental collision, 60 Ma after ophiolite emplacement.

  12. The Relationship between American Counseling Association Members' Professional Affiliations and Advocacy Attitudes and Actions as Defined by the Lange Profession Advocacy Scale

    ERIC Educational Resources Information Center

    Lange, Amber

    2009-01-01

    A sample of American Counseling Association (ACA) members and the entire population of the ACA Legislative Institute attendants was investigated to determine if any variables were contributing to strong scores on the Lange Profession Advocacy Scale (LPAS), a Rasch analyzed instrument. A total of 563 cases had a valid measure score and were…

  13. Formation of ophiolite-bearing tectono-sedimentary mélanges in accretionary wedges by gravity driven submarine erosion: Insights from analogue models and case studies

    NASA Astrophysics Data System (ADS)

    Malavieille, Jacques; Molli, Giancarlo; Genti, Manon; Dominguez, Stephane; Beyssac, Olivier; Taboada, Alfredo; Vitale-Brovarone, Alberto; Lu, Chia-Yu; Chen, Chih-Tung

    2016-10-01

    Orogenic wedges locally present chaotic tectonostratigraphic units that contain exotic blocks of various size, origin, age and lithology, embedded in a sedimentary matrix. The occurrence of ophiolitic blocks, sometimes huge, in such "mélanges" raises questions on (i) the mechanisms responsible for the incorporation of oceanic basement rocks into an accretionary wedge and (ii) the mechanisms allowing exhumation and redeposition of these exotic elements in "mélanges" during wedge growth. To address these questions, we present the results of a series of analogue experiments performed to characterize the processes and parameters responsible for accretion, exhumation and tectonosedimentary reworking of oceanic basement lithospheric fragments in an accretionary wedge. The experimental setup is designed to simulate the interaction between tectonics, erosion and sedimentation. Different configurations are applied to study the impact of various parameters, such as irregular oceanic floor due to structural inheritance, or the presence of layers with contrasted rheology that can affect deformation partitioning in the wedge (frontal accretion vs basal accretion) influencing its growth. Image correlation technique allows extracting instantaneous velocity field, and tracking of passive particles. By retrieving the particle paths determined from models, the pressure-temperature path of mélange units or elementary blocks can be discussed. The experimental results are then compared with observations from ophiolite-bearing mélanges in Taiwan (Lichi and Kenting mélanges) and Raman spectroscopy of carbonaceous material (RSCM) Thermometry data on rocks from the northern Apennines (Casanova mélange). A geological scenario is proposed following basic observations. The tectonic evolution of the retroside of doubly vergent accretionary wedges is mainly controlled by backthrusting and backfolding. The retro wedge is characterized by steep slopes that are prone to gravitational

  14. [The province of East Prussia and "euthanasia" during national socialism: the SS-"Aktion Lange" and "Aktion T4"].

    PubMed

    Topp, Sascha; Fuchs, Petra; Hohendorf, Gerrit; Richter, Paul; Rotzoll, Maike

    2008-01-01

    During World War II, psychiatric patients hospitalized in asylums in Eastern Prussia became victims of two separate killing programmes: first, by the SS-special command Lange, second by the centrally (in Berlin) organized "euthanasia"-"Aktion T4". By an analysis of the patient files of the victims, the present paper shows that the historical actors responsible for the killings were communicating with each other. It is now also possible to reconstruct the exact dynamic in time and space of the killings. A comparative analysis of the selection criteria within the total population of the asylums documents that in both programs, the responsible historical actors included physicians and provincial administrative personnel; it further shows that under the conditions of war, only patients who were able to contribute to the asylum work and economy, and were behaviourally adapted could survive.

  15. Metasomatic Evolution in Tectonically Mixed Zones (Mélange) and Significance for Geochemical Evolution of the Slab-Mantle Interface

    NASA Astrophysics Data System (ADS)

    Bebout, G. E.; King, R. L.

    2012-12-01

    Fluid flow focused in highly deformed zones (shear zones), and the physical juxtaposition of chemically disparate rocks (via mechanical mixing) in such zones, can lead to extensive metasomatism, including volume strain, and result in rocks with hybridized compositions little resembling the compositions of the incorporated rock types [1-5]. In the Catalina Schist (California), lawsonite-albite, lawsonite-blueschist, and amphibolite-facies units contain shear zones at scales of meters to kilometers, each containing "blocks" (with more spherical or more tabular dimensions) co-facial in grade with the "matrix" surrounding these blocks [1-3]. Oxygen isotope data for these "mélange" units, and adjacent more "coherent" expanses, indicate enhanced fluid flow in the more strongly deforming mélange zones while fluid flow in coherent domains was dominantly fracture-controlled and episodic. The amphibolite-facies mélange unit shows evidence for km-scale equilibration of varying mineral assemblages with H2O-rich fluids with uniform O and H isotope compositions consistent with a lower-grade metasedimentary source. This unit is believed to have formed largely by mechanical mixing of mafic and ultramafic compositions, partly because of the scarcity of sedimentary blocks. However, the mélange matrix in this unit preserves a number of sedimentary chemical/isotopic characteristics (e.g., Pb isotope compositions [3]) that could reflect the incorporation of sedimentary rocks, with or without fluid-related fractionation, and possibly fluid-mediated additions. Tectonically mixed zones such as these, if volumetrically significant at the slab-mantle interface, could exert disproportionate control on the compositions of hydrous fluids or silicate melts emanating from subducting slabs and entering the forearc to backarc mantle wedge, including those contributing to arc magmatism [1-5]. Geochemical studies of arc lavas should consider the possibility that the "fluids" contributed from

  16. Williams syndrome

    MedlinePlus

    ... with Williams syndrome may show: A flattened nasal bridge with small upturned nose Long ridges in the ... Alternative Names Williams-Beuren syndrome Images Low nasal bridge References Morris CA. Williams syndrome. In: Pagon RA, ...

  17. Marfan Syndrome

    MedlinePlus

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood ... fibrillin. A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

  18. Sjogren's Syndrome

    MedlinePlus

    Sjogren's syndrome Overview By Mayo Clinic Staff Sjogren's (SHOW-grins) syndrome is a disorder of your immune system ... disorders, such as rheumatoid arthritis and lupus. In Sjogren's syndrome, the mucous membranes and moisture-secreting glands of ...

  19. Structural evolution and deformation kinematics of a subduction-related serpentinite-matrix mélange, Santa Elena peninsula, northwest Costa Rica

    NASA Astrophysics Data System (ADS)

    Escuder-Viruete, Javier; Baumgartner, Peter O.

    2014-09-01

    Detailed structural analysis of the Isla Pelada serpentinite-matrix mélange on Santa Elena Peninsula, Pacific coast of northwest Costa Rica, elucidates for the spatial distribution and temporal progression of a décollement-related deformation. This décollement zone constitutes the fault rock of a plate boundary in a subduction to collision setting. The décollement zone is defined by a thick tectonic mélange that includes blocks and belts of polymictic breccia, turbiditic greywacke, argillite, radiolarite, basalt, gabbro and serpentinized peridotite in a variably foliated serpentinite matrix. The chemical-mineral data of the peridotite blocks in the mélange indicate that they are fragments of abyssal mantle, different of the very depleted forearc mantle peridotites of the overlying Santa Elena ultramafic nappe. The structural evolution of the mélange can be divided into four main events. Early D1 deformation took place during underthrusting in the footwall of the décollement and is characterized by subhorizontal layer-parallel extension and subsequent by heterogeneous shearing of trench-fill deposits, oceanic volcanic rocks and variably serpentinized peridotites, resulting asymmetric boudinage, mesoscopic porphyroclasts and pervasive (S1) S-C fabrics. D1 is followed by layer-parallel contraction with early D2 folding and local development of an S2 pressure-solution cleavage, and late-D2 thrusting and large-scale duplexing. Therefore, D2 deformation evolves from pervasive coaxial subhorizontal contraction to a more localized non-coaxial strain (along relatively narrow thrust surfaces, in the mélange). D2 deformation mainly occurred in the hanging-wall of the décollement and was related to the downward migration of the subduction thrust. The result is the incorporation of slices of the subducted sequence by underplating into the overriding plate, typical of accretionary prisms. Kinematic indicators in the mélange are consistent with a general eastward

  20. Cushing's Syndrome

    MedlinePlus

    ... example, polycystic ovary syndrome can cause menstrual disturbances, weight gain beginning in adolescence, excess hair growth, and impaired insulin action and diabetes. Metabolic syndrome-a combination of ...

  1. "High-grade burial metamorphism of sedimentary mélange, Shoo Fly Complex, central Sierra Nevada, California"

    NASA Astrophysics Data System (ADS)

    Mendoza, Y.; Wakabayashi, J.

    2013-12-01

    blocks are present within sub to lower greenschist facies phyllites. This relationship suggests that much of this unit is a sedimentary mélange. Given the similarity of protoliths, such an origin is probable for the higher-grade rocks but the high-grade metamorphism has obscured obvious differences in metamorphic grade between block and matrix there. This study indicates that the Shoo Fly Complex in this region comprises a subduction complex made up of typical oceanic and trench fill lithologies, with a significant proportion consisting of submarine debris flow deposits (sedimentary mélange). Burial metamorphism reaching upper amphibolite/granulite facies has affected these rocks. Whether this metamorphism resulted from collision/slab breakoff, ridge subduction, or other mechanisms is not clear at this time, but these rocks clearly experienced different a different tectonothermal history than their lower grade equivalents in the northern Sierra.

  2. Sandstone provenance and tectonic evolution of the Xiukang Mélange from Neotethyan subduction to India-Asia collision (Yarlung-Zangbo suture, south Tibet)

    NASA Astrophysics Data System (ADS)

    An, Wei; Hu, Xiumian; Garzanti, Eduardo

    2016-04-01

    The Xiukang Mélange of the Yarlung-Zangbo suture zone in south Tibet documents low efficiency of accretion along the southern active margin of Asia during Cretaceous Neotethyan subduction, followed by final development during the early Paleogene stages of the India-Asia collision. Here we investigate four transverses in the Xigaze area (Jiding, Cuola Pass, Riwuqi and Saga), inquiry the composition in each transverse, and present integrated petrologic, U-Pb detrital-zircon geochronology and Hf isotope data on sandstone blocks. In fault contact with the Yarlung-Zangbo Ophiolite to the north and the Tethyan Himalaya to the south, the Xiukang mélange can be divided into three types: serpentinite-matrix mélange composed by broken Yarlung-Zangbo Ophiolite, thrust-sheets consisting mainly chert, quartzose or limestone sheets(>100m) with little intervening marix, and mudstone-matrix mélange displaying typical blocks-in-matrix texture. While serpentinite-matrix mélange is exposed adjacent to the ophiolite, distributions of thrust-sheets and blocks in mudstone-matrix mélange show along-strike diversities. For example, Jiding transverse is dominant by chert sheets and basalt blocks with scarcely sandstone blocks, while Cuola Pass and Saga transverses expose large amounts of limestone/quartzarenite sheets in the north and volcaniclastic blocks in the south. However, turbidite sheets and volcaniclastic blocks are outcropped in the north Riwuqi transverse with quartzarenite blocks preserved in the south. Three groups of sandstone blocks/sheets with different provenance and depositional setting are distinguished by their petrographic, geochronological and isotopic fingerprints. Sheets of turbiditic quartzarenite originally sourced from the Indian continent were deposited in pre-Cretaceous time on the northernmost edge of the Indian passive margin and eventually involved into the mélange at the early stage of the India-Asia collision. Two distinct groups of volcaniclastic

  3. Emplacement of serpentinites in the Chohar Gonbad-Gugher-Baft ophiolitic mélange, southeast Iran: examination of the mineral-chemical, petrologic, and structural features

    NASA Astrophysics Data System (ADS)

    Mohammadi, N.; Ahmadipour, H.; Lentz, D. R.; Shafaii Moghadam, H.

    2016-03-01

    The Chohar Gonbad-Gugher-Baft ophiolite mélange, located along the major Baft and Shahr-e-Babak fault zones, southeast Iran, represents remnants of Neo-Tethyan oceanic lithosphere. This mélange contains blocks of harzburgite, dunite, lherzolite, basalt, and other ophiolite-related lithologies tectonically mixed with and embedded in a serpentinite matrix. Field, petrographic, and geochemical data show that peridotites in this mélange belong to the upper mantle. They seem to have undergone up to ~20 % partial melting in a supra-subduction zone setting, based on their spinel Cr# values (0.21-0.53). Chemical compositions and textures in the serpentinites indicate that they were partially hydrated during emplacement and further mobilized diapirically to the surface. The different deformation stages occurred in an accretionary wedge environment. Petrographic evidence shows that the first serpentinization event produced mesh-textured serpentinites formed under static conditions in an ocean floor environment (Nain-Baft ocean crust), where the initial lizardite, bastite, and chrysotile veins formed. Plastic deformation occurred due to the subduction of Nain-Baft oceanic lithospheric beneath the central Iranian microcontinent, with antigorite-bearing flare-textured serpentinites produced. During progressive exhumation of the Nain-Baft ophiolite mélange, the serpentinites were affected by ductile, ductile-brittle, and brittle deformation, respectively. Accretion and resultant diapirism are the most important processes in the emplacement of serpentinite, which is a consequence of hydration of the ocean crust. In this example, late-stage emplacement via thrusting occurred along the northern extent of the southern Sanandaj-Sirjan zone (S-SZ).

  4. Accessory minerals and subduction zone metasomatism: a geochemical comparison of two mélanges (Washington and California, U.S.A.)

    USGS Publications Warehouse

    Sorensen, Sorena S.; Grossman, Jeffrey N.

    1993-01-01

    Data from the Gee Point and Catalina mélanges suggest that the accessory minerals titanite, rutile, apatite, zircon and REE-rich epidote play a significant role in the enrichment of trace elements in both mafic and ultramafic rocks during subduction-related fluid-rock interaction. Mobilization of incompatible elements, and deposition of such elements in the accessory minerals of mafic and ultramafic rocks may be fairly common in fluid-rich metamorphic environments in subduction zones.

  5. Neotethyan rifting-related ore occurrences: study of an accretionary mélange complex (Darnó Unit, NE Hungary)

    NASA Astrophysics Data System (ADS)

    Kiss, Gabriella B.; Oláh, Erika; Zaccarini, Federica; Szakáll, Sándor

    2016-02-01

    The geology of the NE Hungarian Darnó Unit is rather complicated, as it is composed mostly of a Jurassic accretionary mélange complex, according to the most recent investigations. The magmatic and sedimentary rock blocks of the mélange represent products of different evolutionary stages of the Neotethys; including Permian and Triassic sedimentary rocks of marine rifting related origin, Triassic pillow basalt of advanced rifting related origin and Jurassic pillow basalt originated in back-arc-basin environment. This small unit contains a copper-gold occurrence in the Permian marly-clayey limestone, an iron enrichment in the Triassic sedimentary succession, a copper-silver ore occurrence in Triassic pillow basalts and a copper ore indication, occurring both in the Triassic and Jurassic pillow basalts. The present study deals with the Cu(-Ag) occurrence in the Triassic basalt and the Fe occurrence in the Triassic sedimentary succession. The former shows significant similarities with the Michigan-type mineralizations, while the latter has typical characteristics of the Fe-SEDEX deposits. All the above localities fit well into the new geological model of the investigated area. The mineralizations represent the different evolutionary stages of the Neotethyan rifting and an epigenetic, Alpine metamorphism-related process and their recent, spatially close position is the result of the accretionary mélange formation. Thus, the Darnó Unit represents a perfect natural laboratory for studying and understanding the characteristic features of several different rifting related ore forming processes.

  6. K-Ar age of mica clay minerals in an ultracataclasite of a fossil seismogenic fault in the Mugi Mélange, Shimanto accretionary complex, southwest Japan

    NASA Astrophysics Data System (ADS)

    Tonai, S.; Ito, S.; Hashimoto, Y.; Tamura, H.

    2015-12-01

    We used the K-Ar ages of clay-sized mineral grains to investigate the timing of activity on the fossil seismogenic Minami-Awa Fault, which separates coherent strata of the Shimanto accretionary complex to its north from tectonic mélange to south. The K-Ar ages from the matrix shale of the mélange range from 85 to 48 Ma and decrease with decreasing grain size, indicating that they record a mixture of authigenic illite and detrital mica. In contrast, the K-Ar ages of an ultracataclasite within the fault core are significantly younger, ranging from 29 to 23 Ma, and are unrelated to grain size. This indicates that 40Ar diffused completely from the ultracataclasite between 29 and 23 Ma, which postdates the formation of authigenic illite by about 20 Myr. The diffusion of 40Ar in the ultracataclasite was probably caused by frictional heating or high-temperature fluid migration that occurred when the fault was reactivated. The results indicate that seismogenic faults that separate tectonic mélange from coherent strata in accretionary complexes may slip, not only during accretion, but also long after accretion.

  7. Rock slope stability assessment by using RMRB and SMR methods for future development around Gunung Lang, Ipoh, Perak

    NASA Astrophysics Data System (ADS)

    Kamaruszaman, Norazliza; Jamaluddin, Tajul Anuar

    2016-11-01

    The unfavourably oriented discontinuities with respect to the slope cutting orientation may results in rock slope failure or instabilities. The main factor that influences the rock slope stability is the geological factors. The role of geology on slope problems and assessment is variable, according to the subsoil constituent and structures itself. Generally, rock masses are contains a plane of weaknesses such as fault, joint, bedding plane, foliation, dyke, folds, etc. Therefore, those structures will drive a rock mass on a slope to break down. Geological processes also play the role in the rock slope stability. These are due to weathering (expose with air and water), surface erosion, seepage occurs along open joints and the chemical reaction in the intact rock with water that produce high porosity (e.g. limestone). To determine the instabilities of rock falls, basic rock mass rating (RMRb) and slope mass rating (SMR) assessment were conducted on rocks slope in Gunung Lang. The study area is divided into three slope zone; GL-1, GL-2 and GL-3. The results indicates that the rock slopes have two possible modes of failure consisting of planar failure and wedge failures. Rock slope GL-1 is relatively in stable condition. Rock slope GL-2 has potential mode of wedge failure. The slope is considered as partially stable and its probability of failure is 40%. Rock slope GL-3 have potential modes of wedge and planar failures. Therefore, the slope is considered as unstable and its probability of failure is 60%.

  8. Lang and Goulet Hardiness Scale: development and testing on bereaved parents following the death of their fetus/infant.

    PubMed

    Lang, Ariella; Goulet, Celine; Amsel, Rhonda

    2003-12-01

    The process of development and testing of the Lang and Goulet Hardiness Scale (LGHS), a self-report instrument designed to measure hardiness in bereaved parents following the death of their fetus/infant, is presented. Hardiness is a personal resource, composed of 3 interdependent components that are characterized by a sense of personal control over the outcome of life events and hardships such as the death of a fetus/infant, an active orientation toward meeting the challenges brought on by the loss, and a belief in the ability to make sense of one's own existence following such a tragedy. The concept of hardiness has been studied by various disciplines and in a multitude of settings to understand its ability to lessen potentially negative effects of life stress. However, it has never been studied within the context of parental bereavement. The LGHS was developed systematically, originating from a concept analysis. A panel of 15 experts was used to establish content validity.A pretest was conducted on 73 bereaved individuals to assess convergent and discriminant validity of the LGHS. Subsequently, a validation study on 220 bereaved parents who had experienced the death of their fetus/infant 2 months previously was conducted including a retest 6 months after the loss with 192 of the remaining participants. Analyses reveal that the LGHS is a valid and reliable instrument for measuring hardiness and that it is sensitive enough to detect changes in the construct over time.

  9. Remnants of a hyperextended passive margin in a Caledonian mélange unit below the Jotun nappe, B\\overdalen, Central-south Norway

    NASA Astrophysics Data System (ADS)

    Alsaif, Manar; Jakob, Johannes; Andersen, Torgeir; Corfu, Fernando

    2015-04-01

    The Scandinavian Caledonides have been long studied, yet their ever unfolding complexity renders them far from being fully understood. It has been recognized that the Caledonian Allochthons have neither a linear nor straightforward along-strike relationship (Corfu et al. 2014). A mélange unit has been recently identified as a separate tectonic unit (Andersen et al. 2012). This unit is structurally positioned below crystalline nappes previously assigned to the Middle Allochthon. The mélange comprises meta-sediments and minor meta-basalt/gabbro, but most intriguingly, numerous solitary meta-peridotites. These occur as 'Alpine type' meta-peridotites, serpentinites, soapstones and detrital serpentinites. We present results of a field study of the mélange in the B\\overdalen area, structurally below the Jotun nappe, and suggest that this provides further evidence that the regional mélange unit was formed in a hyperextended passive margin. The meta-peridotites represent exhumed serpentinized mantle and are intimately associated with meta-sediments. The sediments are garnetiferous chlorite-muscovite schists, graphitic schists, phyllites, amphibolites, meta-sandstones as well as quartzite-pebble dominated conglomerates. It is suggested that this highly heterogeneous unit formed during the early stages of rifting and hyperextension along the Baltican passive margin. Characteristics of the detrital peridotites suggests that serpentinite-talc protrusions may have formed islands. The processes involved are observed on modern margins where the best-studied example is the Iberia-Newfoundland passive margin. Work in present-day margins (mostly seismic reflection data) elucidate the large-scale structure of hyperextended margins, while studies of ancient exposed examples in mountain belts provide insight into the lithology, geochemistry and details of these margins. The widespread distribution of hyperextended margins in modern margins and the increasing number of recognizable

  10. Magmatic origin of low-T mafic blueschist and greenstone blocks from the Franciscan mélange, San Simeon, California

    NASA Astrophysics Data System (ADS)

    Ukar, Estibalitz; Cloos, Mark

    2015-08-01

    The Franciscan mélange exposure near San Simeon contains abundant greenstone and minor blueschist blocks that were tectonically boudinaged while encased in the shale-matrix. Tectonic deformation of the blueschists is evident from variable amounts of cataclastic flow along their margins and in pinched tails. Major, trace, and rare earth elemental analyses indicate that blueschist and greenstone blocks in this area of the mélange were derived from sources with MORB-like composition along with some having trace element and REE patterns similar to OIB compositions. Most blocks are low LREE basalts that probably formed in an open ocean ridge setting, but some blocks have high LREE contents similar to off-axis seamounts. Linear trends of incompatible elements for both blueschist and greenstone blocks indicate that both lithologies were probably derived from a similar, variably fractionated, tholeiitic magma. Blueschist blocks with sodic amphibole + lawsonite ± epidote were pervasively recrystallized at 300-350 °C and foliated during ductile deformation that included folding. Their protolith can only be identified as mafic. A few blocks contain very small amounts of metasedimentary materials indicating some were probably seafloor basalts, but some may have been diabase or even gabbro. Where interlayered sediment was present, the mafic protolith was enriched in K, Rb, and Na. Greenstones, on the other hand, contain abundant pseudomorphic evidence of magmatic textures. Alteration to albite, chlorite and pumpellyite at temperatures of 100-200 °C is intense, especially in cataclastic margins and pinched tails. Some of the basaltic greenstones have attached radiolarian chert, and a few have relict diabasic textures. The mafic blueschists and greenstones in the mélange near San Simeon are probably fragments from the uppermost part of the Farallon plate. The blueschists may be mostly mafic slabs uprooted from the subducting crust, underplated to the base of the North

  11. Structural and metamorphic evolution of an ocean-continent transition (OCT) zone mélange deformed under HP conditions during Alpine subduction (Western Italian Alps)

    NASA Astrophysics Data System (ADS)

    Gosso, G.; Benciolini, L.; Dilek, Y.; Festa, A.; Spalla, M.; Tartarotti, P.

    2011-12-01

    We report on the structural architecture and metamorphic evolution of a mélange, developed originally in an ocean-continent transition (OCT) zone along the boundary between the continental crust of the Sesia-Lanzo (SLZ) and the oceanic Piemonte Zones (PZ) in the axial part of the Western Alps. All these units were deformed together under high-pressure conditions. The mélange consists of thin layers of calcschist, fine-grained gneiss, quartzite, minor metabasic rocks and serpentinite, and occurs all along the western margin of southern SLZ, extending from Santanel klippe to Lanzo Massif, over a distance of 50 km (Spalla et al., 1983; Battiston et al., 1984). Calcschist rocks range from phyllites to carbonatic schists and marbles; fine-grained gneisses of continental origin (very similar to those of SLZ) include phengitic white mica, chlorite, ± garnet ± albite and relict allanite. Thinly layered quartzites are white mica- and garnet-bearing. Metabasic rocks consist of metagabbros and metabasalts with minor mylonitic serpentinites. All these lithologies of the mélange unit and the rocks of SLZ and PZ together underwent four episodes of deformation, giving rise to a complex regional tectonostratigraphy. The earliest deformational structures are represented by up to ten meter-scale isoclinal rootless folds. The metamorphic mineral assemblages marking successive foliations indicate that all rock units in the mélange, SLZ and PZ (Spalla et al., 1983; Benciolini et al., 1984) experienced an early eclogite facies imprint, followed by re-equilibration under blueschist facies conditions, and that they were finally widely retrogressed under greenschist facies conditions during the last two deformational episodes (D3 and D4 structures). The strong synmetamorphic deformation of this mélange prevents an unequivocal interpretation of its origin; hence, we envisage two possible scenarios: i) the present day configuration of these thin, intermingled layers, including

  12. Two Cases of LQT Syndrome with Malignant Syncope after Switch from Propranolol to Bisoprolol.

    PubMed

    Kesek, Milos; Rydberg, Annika; Jensen, Steen M

    2016-03-01

    Propranolol in slow-release form has been the first-line treatment in long QT (LQT) until it was withdrawn from the market. We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5 mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange-Nielsen syndrome, previous gangliectomy, and ICD implantation, switched to bisoprolol 5 mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months.

  13. Metabolic syndrome

    MedlinePlus

    Insulin resistance syndrome; Syndrome X ... middle and upper parts of the body (central obesity ). This body type may be described as "apple-shaped." Insulin resistance. Insulin is a hormone produced in the pancreas. ...

  14. Marfan Syndrome

    MedlinePlus

    ... Like for Kids With Marfan Syndrome? en español Síndrome de Marfan Evan couldn't wait for school ... for Marfan syndrome runs in families, getting passed down to children from parents who have the disease. ...

  15. Dumping Syndrome

    MedlinePlus

    ... Syndrome Related Topics Section Navigation Digestive Diseases Abdominal Adhesions Acid Reflux (GER & GERD) in Adults Definition & Facts ... Eating, Diet, & Nutrition Clinical Trials Cyclic Vomiting Syndrome Dental Enamel Defects and Celiac Disease Dermatitis Herpetiformis Dermatitis ...

  16. Aicardi Syndrome

    MedlinePlus

    ... Girls with Aicardi syndrome have varying degrees of intellectual disability and developmental delay. Many girls also have developmental ... Girls with Aicardi syndrome have varying degrees of intellectual disability and developmental delay. Many girls also have developmental ...

  17. Malabsorption Syndromes

    MedlinePlus

    ... the foods you eat. If you have a malabsorption syndrome, your small intestine cannot absorb nutrients from foods. Causes of malabsorption syndromes include Celiac disease Lactose intolerance Short bowel ...

  18. Rett Syndrome

    MedlinePlus

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  19. Horner syndrome

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000708.htm Horner syndrome To use the sharing features on this page, please enable JavaScript. Horner syndrome is a rare condition that affects the nerves ...

  20. Marfan Syndrome

    MedlinePlus

    ... Like for Kids With Marfan Syndrome? en español Síndrome de Marfan Evan couldn't wait for school ... for Marfan syndrome runs in families, getting passed down to children from parents who have the disease. ...

  1. Down Syndrome

    MedlinePlus

    ... cells is caused by abnormal cell division after fertilization. Translocation Down syndrome. Down syndrome can also occur ... one option available for couples undergoing in vitro fertilization who are at increased risk of passing along ...

  2. LEOPARD syndrome

    MedlinePlus

    LEOPARD syndrome is a very rare inherited disorder in which there are problems with the skin, face, ... LEOPARD syndrome is inherited as an autosomal dominant trait. This means the person only needs the abnormal ...

  3. Myelodysplastic Syndromes

    MedlinePlus

    ... help with blood clotting. If you have a myelodysplastic syndrome, the stem cells do not mature into healthy ... can lead to infection, anemia, or easy bleeding. Myelodysplastic syndromes often do not cause early symptoms and are ...

  4. Klinefelter Syndrome

    MedlinePlus

    ... testicles, which can lead to lower production of testosterone. The syndrome may also cause reduced muscle mass, ... caused by Klinefelter syndrome are related to low testosterone (hypogonadism). Testosterone replacement therapy reduces the risk of ...

  5. 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 ...

  6. Turner Syndrome

    MedlinePlus

    ... at increased risk of developing weak, brittle bones (osteoporosis). Pregnancy complications. Most women with Turner syndrome are infertile. ... loss, eye problems, high blood pressure, diabetes and osteoporosis. Periodic ... Pregnancy and fertility treatment Few women with Turner syndrome ...

  7. Marfan syndrome

    MedlinePlus

    Marfan syndrome is a disorder of connective tissue. This is the tissue that strengthens the body's structures. Disorders ... Marfan syndrome is caused by defects in a gene called fibrillin-1. Fibrillin-1 plays an important role ...

  8. Apert Syndrome.

    PubMed

    Datta, Saikat; Saha, Sandip; Kar, Arnab; Mondal, Souvonik; Basu, Syamantak

    2014-09-01

    Apert syndrome is one of the craniosynostosis syndromes which, due to its association with other skeletal anomalies, is also known as acrocephalosyndactyly. It is a rare congenital anomaly which stands out from other craniosynostosis due to its characteristic skeletal presentations.

  9. Turcot Syndrome

    MedlinePlus

    ... types of brain tumors in Turcot syndrome are: Glioblastoma . This type of brain tumor is a very ... to generation in a family. In families with glioblastoma and other features of Lynch syndrome, mutations (alterations) ...

  10. Proteus Syndrome

    MedlinePlus

    ... Donate Cash Donation Life Insurance Gift Matching Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome ... approved by the Proteus Syndrome Foundation Assessment and management of the orthopedic and other complications of Proteus ...

  11. Edwards' syndrome.

    PubMed

    Crawford, Doreen; Dearmun, Annette

    2016-12-08

    Edwards' syndrome is a serious genetic condition that affects fetal cellular functions, tissue development and organogenesis. Most infants with the syndrome are female, but there is no race predominance.

  12. Turner Syndrome

    MedlinePlus

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or incomplete ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of skin ...

  13. Craniofacial Syndrome Descriptions

    MedlinePlus

    ... Dysplasia Goldenhar/Hemifacial Moebius syndrome Pfeiffer syndrome Pierre Robin Sequence Treacher Collins syndrome Other syndromes Wonder News & ... absence of the radial limb. Pfeiffer syndrome Pierre Robin Sequence Saethre-Chotzen Saethre-Chotzen syndrome is a ...

  14. Velocardiofacial Syndrome

    ERIC Educational Resources Information Center

    Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

    2009-01-01

    Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the…

  15. Velocardiofacial Syndrome

    ERIC Educational Resources Information Center

    Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

    2009-01-01

    Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the…

  16. Fraser syndrome.

    PubMed

    Kalpana Kumari, M K; Kamath, Sulata; Mysorekar, Vijaya V; Nandini, G

    2008-01-01

    Fraser syndrome or cryptophthalmos is a rare autosomal recessive disorder characterized by major features such as cryptophthalmos, syndactyly and abnormal genitalia. The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy. We present the autopsy findings of a rare case of Fraser syndrome in a male infant.

  17. Complexities of Eruptive Processes at Mariana Forearc Serpentinite Mud Volcanoes and Implications for Serpentinite Mélange Development

    NASA Astrophysics Data System (ADS)

    Fryer, P.; Becker, N. C.; Wheat, C. G.; Hulme, S.; Fryer, G. J.; Gharib, J.; Mottl, M. J.

    2003-12-01

    Detailed DSL120 side-scan sonar surveys and Jason2/Medea ROV observations of the summit areas of several serpentinite mud volcanoes on the eastern half of the Mariana forearc reveal vent dimensions and information about the size and dynamics of mud protrusions emanating from the vents. Some vents appear to be small (a few km in diameter), which suggests narrow conduits beneath the mud volcanoes. Other sites of mud flow emanation appear to be along fissures a few tens to hundreds of m long. New high-resolution bathymetry of the seamounts shows details of the seamount flanks that confirm multiple lobes of mud protrusions and show evidence of catastrophic collapse events, possibly associated with pulses of larger-volume fluid egress. The collapse events scour channels in the sides of the edifices and in some instances distribute large volumes of material about the base of the seamounts. The debris shed from the edifices can extend for tens of kilometers outward from the flanks of the edifices. The seamounts are clearly subject to large-scale episodic disruption. Some bear fault traces throughout the edifices. Shallow earthquake activity in the Mariana forearc is largely confined to the outer 100-km zone of faulting and serpentinite seamount formation. Fault zones in the outer forearc control canyons that probably channel debris from the seamounts toward the trench axis. The wide-spread distribution and reworking of debris shed from the mud volcano edifices and from fault-exposed serpentinite provides a model for the formation of complex serpentinite mélange deposits in exotic terranes, such as the Franciscan of California.

  18. Syndromic deafness-prevalence, distribution and hearing management protocol in Indian scenario

    PubMed Central

    Arumugam, Senthil Vadivu; Paramasivan, Vijaya Krishnan; Murali, Sathiya; Natarajan, Kiran; Sudhamaheswari; Kameswaran, Mohan

    2015-01-01

    Background The estimated prevalence of Sensory Neural Hearing Loss (SNHL) in patients less than 18 years of age is 6 per 1000. Roughly 50% of cases of congenital SNHL can be linked to a genetic cause, with approximately 30% being syndromic and the remaining 70% being non-syndromic. The term “syndromic” implies the presence of other distinctive clinical features in addition to hearing loss. The aim of our study was to find the distribution of various Syndromic associations in patients with profound deafness, presented at Madras ENT Research foundation, Chennai and to formulate a management protocol for these patients and to discuss in detail about the clinical features of commonly encountered syndromic deafness. Materials and methods Our retrospective study was aimed at describing the various Syndromic associations seen in patients with congenital profound deafness. Information was collected from the medical records. At our centre all patients undergo a comprehensive evaluation. The distribution, etiological factors and management protocol for various syndromes are here presented. Results Out of 700 patients with congenital profound deafness all patients with Syndromic associations (n = 35) were studied. 5% of profoundly deaf candidates were found to be syndromic. Most common syndrome in our series was found to be congenital rubella syndrome followed by Jervell and Lange-Nielsen syndrome. Conclusion Congenital deafness is an associated feature of many syndromes. Detailed history taking with comprehensive evaluation is mandatory to rule out the associated syndromes. Diagnosis must be confirm by a genetic study. Multidisciplinary approach is essential for appropriate diagnosis and management. PMID:26005567

  19. [Autoinflammatory syndrome].

    PubMed

    Ida, Hiroaki; Eguchi, Katsumi

    2009-03-01

    The autoinflammatory syndromes include a group of inherited diseases that are characterized by 1) seemingly unprovoked episodes of systemic inflammations, 2) absence of high titer of autoantibody or auto-reactive T cell, and 3) inborn error of innate immunity. In this article, we will focus on the clinical features, the pathogenesis related the genetic defects, and the therapeutic strategies in the representative disorders including familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), hyper-IgD with periodic fever syndrome (HIDS), syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA), and Blau syndrome. Recent advances in genetics and molecular biology have proceeded our understanding of the pathogenesis of autoinflammatory syndromes.

  20. P-T-t Paths and Tectonic History of Low-T Blueschists from the Franciscan Mélange, San Simeon, California

    NASA Astrophysics Data System (ADS)

    Ukar, E.; Cloos, M.

    2011-12-01

    The Franciscan mélange is perhaps the most famous blueschist-bearing, pelitic-matrix mélange in the world. Most previous studies of Franciscan blueschists have focused on high-T, garnet-bearing blocks from the Central Belt north of San Francisco. Low-T blueschist blocks are ubiquitous and more abundant, but they have remained largely unstudied. The low-T (only) blueschist-bearing mélange exposure along 6 + km of nearly continuous seacliffs and wavecut benches near San Simeon offers the perfect location for a detailed study of low-T blueschist blocks. Petrographic analyses aided by backscattered electron imaging, microprobe mineral and bulk chemistry analyses, and thermodynamic calculations reveal these blueschists experienced a counterclockwise P-T path. Peak T and P conditions for epidote-bearing blueschists are estimated to be 325-350°C at pressures of 5-9 kbar. Many blocks have textural evidence of lawsonite replacing epidote and Na-amphibole with Fe+3-rich rims, which occurred as the rocks cooled below ~250°C at ~5 kbar. Nine of the 34 blocks studied have an associated actinolitic rind along the margins, which, previous to this study, were thought to be unique to high-T, garnet-bearing, mafic blueschist and eclogite blocks. 40Ar-39Ar geochronological data were obtained from phengite separates from four low-T blueschist blocks and from an actinolitic rind associated with one of the blocks. Three of the blocks yield ages between 154 ± 2 to 152 ± 1.8 Ma, while the actinolitic rind yields an age of 150.9 ± 1 Ma. These new ages are from the part of the Franciscan west of the San Andreas fault that moved northwards at least 300 km with respect to the larger exposures of the Franciscan that are east of the fault. These ages are similar to those reported for high-T blocks in northern mélange exposures, which indicates both high- and low-T mafic Franciscan blueschists must have formed contemporaneously along 1000+ km of the North American plate margin starting

  1. Andesitic crustal growth via mélange partial melting: Evidence from Early Cretaceous arc dioritic/andesitic rocks in southern Qiangtang, central Tibet

    NASA Astrophysics Data System (ADS)

    Hao, Lu-Lu; Wang, Qiang; Wyman, Derek A.; Ou, Quan; Dan, Wei; Jiang, Zi-Qi; Yang, Jin-Hui; Li, Jie; Long, Xiao-Ping

    2016-05-01

    Deciphering the petrogenesis of andesitic/dioritic rocks is fundamental to understanding the formation of the continental crust. Here we present detailed petrology, geochronology, major and trace element, Sr-Nd-Hf-O isotope data for the Early Cretaceous (˜122 Ma) dioritic rocks in the Bizha area in southern Qiangtang, Tibet. The dioritic rocks are characterized by large ion lithophile elements, Pb, and light rare earth elements but depletion of high field strength elements with slightly enriched and variable ɛNd(t) values of -0.01 to -3.31 and initial 87Sr/86Sr isotopic ratios of 0.7053-0.7062. They also have variable magmatic zircon Hf-O isotope compositions (ɛHf(t) = -5.3 to +3.6 and δ18O = +7.3 to +9.5 ‰). Combined with contemporary andesitic lavas in southern Qiangtang, we suggest that the intermediate magmatic rocks in this area were most probably derived by partial melting of a subduction mélange, which is a mixture of mid-oceanic ridge basalts (MORBs), sediments, and mantle wedge peridotites, formed along the interface between the subducted slab and the overlying mantle wedge in a subduction channel before ˜124 Ma. The mélange diapir melting was triggered by the asthenospheric upwelling and hot corner flow caused by roll-back of the northward subducted Bangong-Nujiang oceanic slab during the Early Cretaceous. The Early Cretaceous intermediate magmatic rocks in southern Qiangtang have an overall continental crust-like andesitic composition. Therefore, partial melting of mélange provides an important support for the generation of andesitic magmas in continental arcs and the "andesite model" for crustal growth.

  2. lange versus forearc contributions to sedimentation and uplift, during rapid denudation of a young Banda forearc-continent collisional belt

    NASA Astrophysics Data System (ADS)

    Duffy, Brendan; Kalansky, Julie; Bassett, Kari; Harris, Ron; Quigley, Mark; van Hinsbergen, Douwe J. J.; Strachan, Lorna J.; Rosenthal, Yair

    2017-05-01

    New sedimentary geochemistry and petrographic analyses provide the most extensive sedimentary documentation yet of the rapid denudation of the young Timor orogen. The data from three basins including two widely-separated, well-dated sections of the Synorogenic Megasequence of Timor-Leste, and a re-dated DSDP 262, constrain the source and timing of detrital sediment flux during forearc-continent collision along the Timor sector of the Banda Arc. The exhumed synorogenic piggy-back basins formed above a mélange unit that developed at the expense of a weak stratigraphic horizon in the Mesozoic stratigraphy, and was exhumed to the sea floor in latest Messinian time. Following an interval of deep marine chalky marl sedimentation, an increasingly muddy sediment flux indicates that the island of Timor became emergent and shed sediment by 4.5 Ma. Comparison of exhumed sections with similar patterns in the DSDP262 chemistry suggests that the sediment source was probably located some 50-60 km distant from the basin, which is consistent with the Aileu region of Timor-Leste that shows an appropriate exhumation history. All sedimentation between 4.5 and 3.2 Ma was probably derived from a low-relief, rapidly eroding, and mudstone-dominated landscape with geochemical affinities to the Triassic-mudstone-derived synorogenic mélange. The mélange unit overlies and surrounds the Banda Terrane, and was presumably structurally emplaced by propagation of a decollement through the Triassic rocks during the collision. After 3.2 Ma, sedimentation was dominated by hard rock lithologies of the Banda Terrane, consisting of forearc cover and basement, the latter including elements of metamafic rocks and metapelites. This phase of sedimentation was accompanied by rapid uplift, which may have been partly driven by a transient imbalance between rock uplift and denudation as resistant lithologies emerged from below mélange-like mudstone. Previous work has suggested that the timing of collision

  3. [Autoinflammatory syndromes].

    PubMed

    Lamprecht, P; Gross, W L

    2009-06-01

    In its strict sense, the term "autoinflammatory syndromes" comprises the hereditary periodic fever syndromes (HPF), which are caused by mutations of pattern-recognition receptors (PRR) and perturbations of the cytokine balance. These include the crypyrinopathies, familial Mediterranean fever, TNF-receptor associated periodic fever syndrome (TRAPS), hyper-IgD and periodic syndrome (HIDS), pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, NALP12-HPF, and the Blau syndrome. The diseases are characterized by spontaneous activation of cells of the innate immunity in the absence of ligands. Autoantibodies are usually not found. HPF clinically present with recurrent fever episodes and inflammation, especially of serosal and synovial interfaces and the skin. Intriguingly, PRR-mediated autoinflammtory mechanisms also play a role in a number of chronic inflammatory and autoimmune diseases.

  4. Overgrowth Syndromes

    PubMed Central

    Edmondson, Andrew C.; Kalish, Jennifer M.

    2015-01-01

    Numerous multiple malformation syndromes associated with pathologic overgrowth have been described and, for many, their molecular bases elucidated. This review describes the characteristic features of these overgrowth syndromes, as well as the current understanding of their molecular bases, intellectual outcomes, and cancer predispositions. We review syndromes such as Sotos, Malan, Marshall–Smith, Weaver, Simpson–Golabi–Behmel, Perlman, Bannayan–Riley–Ruvalcaba, PI3K-related, Proteus, Beckwith–Wiedemann, fibrous dysplasia, Klippel–Trenaunay–Weber, and Maffucci. PMID:27617124

  5. Gorlin syndrome.

    PubMed

    Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

    2013-05-01

    Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

  6. Proteus Syndrome Foundation

    MedlinePlus

    ... Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome Foundation The Proteus Syndrome Foundation , a 501c3 ... 1 Trial with ARQ 092 in Proteus Syndrome Proteus Syndrome Patient Registry The Proteus Syndrome Foundation Contact ...

  7. Plutonic rocks in the Mineoka-Setogawa ophiolitic mélange, central Japan: Fragments of middle to lower crust of the Izu-Bonin-Mariana Arc?

    NASA Astrophysics Data System (ADS)

    Ichiyama, Yuji; Ito, Hisatoshi; Hokanishi, Natsumi; Tamura, Akihiro; Arai, Shoji

    2017-06-01

    A Paleogene accretionary complex, the Mineoka-Setogawa Belt, is distributed around the Izu Collision Zone, central Japan. Plutonic rocks of gabbro, diorite and tonalite compositions are included as fragments and dykes in an ophiolitic mélange in this belt. Zircon U-Pb dating of the plutonic rocks indicates that they were formed at ca. 35 Ma simultaneously. These ages are consistent with Eocene-Oligocene tholeiite and calc-alkaline arc magmatism in the Izu-Bonin-Mariana (IBM) Arc and exclude several previous models for the origin of the Mineoka-Setogawa ophiolitic rocks. The geochemical characteristics of these plutonic rocks are similar to those of the Eocene-Oligocene IBM tholeiite and calc-alkaline volcanic rocks as well as to the accreted middle crust of the IBM Arc, the Tanzawa Plutonic Complex. Moreover, their lithology is consistent with those of the middle and lower crust of the IBM Arc estimated from the seismic velocity structure. These lines of evidence strongly indicate that the plutonic rocks in the Mineoka-Setogawa ophiolitic mélange are fragments of the middle to lower crust of the IBM Arc. Additionally, the presence of the Mineoka-Setogawa intermediate to felsic plutonic rocks supports the hypothesis that intermediate magma can form continental crust in intra-oceanic arcs.

  8. Stratal disruption and development of mélange, Western Newfoundland: effect of high fluid pressure in an accretionary terrain during ophiolite emplacement

    NASA Astrophysics Data System (ADS)

    Waldron, J. W. F.; Turner, D.; Stevens, K. M.

    The Bay of Islands Ophiolite was emplaced onto the continental margin of North America during the mid-Ordovician Taconic orogeny, when tectonic slices of continental margin sediments were accreted to the moving allochthon. Tectonic slices grade into and are surrounded by mélange. Early fracture in sandstones formed without grain breakage and allowed penetration of liquid petroleum along fracture planes. Other fractures involved cataclastic flow and were sometimes re-activated during formation of later pressure solution cleavage. Shear-fracture and extension-fracture boudinage affect competent strata; extensional veins cut cement in limestone beds and are filled by shale, quartz, calcite and bitumen. Folds also formed, at a time when siltstone and sandstone were at least partially lithified. Mélange matrix shows abundant shear and extension fractures in a variety of orientations. Coaxial extension responsible for disruption of bedding can be explained by a brittle accretionary wedge model in which high fluid pressures resulted from tectonic dewatering of shales. Surface slope decreased as fluid pressure rose beneath the ophiolite, causing horizontal extension of the wedge. After escape of excess water the surface slope steepened again as renewed stacking occurred.

  9. Peak metamorphic temperatures from Raman Spectroscopy on Carbonaceous Matter (RSCM) and δ18O and δ13C (carb) isotope composition of a major mélange zone in the South Norwegian Caledonides

    NASA Astrophysics Data System (ADS)

    Jakob, Johannes; Beyssac, Olivier; Boulvais, Philippe; Andersen, Torgeir B.

    2016-04-01

    A mélange in southern Norway comprises a matrix of garnet, mica- and black carbonaceous schists and phyllites of abyssal origin, interlayered with originally coarser grained siliciclastic metasediments, serpentinite conglomerates and sandstones, solitary metaperidotites and thin slivers of gneisses. Several models for the formation of the mélange have been suggested, including formation as a) an ophiolitic mélange formed during ophiolite obduction, b) an unconformable post-obduction transgressive sequence or c) a mélange formed during hyperextension along the pre-Caledonian margin of Baltica. In the past, the mélange has therefore not been treated as one single tectonic unit, but has been assigned to various tectonic positions with both outboard Iapetus and inboard Baltican origins. In this study we argue that the mélange occupies a tectonostratigraphic position below major Baltican basement nappe-complexes previously assigned to the Middle Allochthon. Furthermore, we present new consistent results on the peak metamorphic temperatures (T ˜ 500° C), based on RSCM, and a characteristic δ18Ocarb isotope composition (11-15.5 ‰ SMOW), both consistent for more than 250 km along strike of the mélange. δ13Ccarb values fall within three clusters around 1, - 2 , and - 7 ‰ (PDB), respectively. The stable isotope investigation presented here was carried out in order to explore if pre-Caledonian isotope signatures in various generations of carbonate veins and the early Ordovician fossils at Otta, could have been preserved through a later Caledonian metamorphic overprint. The results presented here however, suggest that re-equilibration of the carbonates took place in the Silurian, most likely coeval with peak metamorphism of ˜ 500° C at ˜ 420 Ma, and the main fabric development close to the base of the nappe-stack. Re-equilibration of the carbonates was assisted by the presence a pervasive static fluid, allowing for oxygen isotope exchange with the surrounding

  10. Cardiorenal syndrome

    PubMed Central

    2009-01-01

    Kidney dysfunction in patients with heart failure and cardiovascular disorders in patients with chronic kidney disease are common. A recently proposed consensus definition of cardiorenal syndrome stresses the bidirectional nature of these heart-kidney interactions. The treatment of cardiorenal syndrome is challenging, however, promising new therapeutic options are currently being investigated in recent and ongoing clinical trials. PMID:20948701

  11. Poland syndrome.

    PubMed

    Sharma, Chandra Madhur; Kumar, Shrawan; Meghwani, Manoj K; Agrawal, Ravi P

    2014-01-01

    Poland's syndrome is a rare congenital condition, characterized by the absence of the sternal or breastbone portion of the pectoralis major muscle, which may be associated with the absence of nearby musculoskeletal structures. We hereby report an 8-year-old boy with typical features of Poland syndrome, the first documented case from Uttar Pradesh, India.

  12. Marfan Syndrome

    MedlinePlus

    ... Connective tissue helps support all parts of your body. It also helps control how your body grows and develops. Marfan syndrome most often affects ... A mutation, or change, in the gene that controls how the body makes fibrillin causes Marfan syndrome. Fibrillin is a ...

  13. Tourette Syndrome.

    ERIC Educational Resources Information Center

    Look, Kathy

    Tourette Syndrome has a history of being misdiagnosed or undiagnosed due to its unusual and complex symptoms. This paper describes: the symptoms of Tourette Syndrome; its etiology; age of onset; therapeutic methods, such as drug therapy, psychotherapy, diet control, and hypnosis; educational implications; and employment prospects. Several…

  14. [Gorlin's syndrome].

    PubMed

    do Amaral, B; Costa e Sousa, R; Moreira, C G

    1997-05-01

    The major features of the nevoid basal-cell carcinoma syndrome are epidermal multiple cell carcinomas, cysts of the jaws and skeletal abnormalities, mainly in the ribs. The authors have reviewed the literature concerning multiple anomalies which are associated to this syndrome, and report a clinical case, emphasizing the advantages of early diagnosis, mainly for dermal and maxillary lesions.

  15. Tourette Syndrome.

    ERIC Educational Resources Information Center

    Look, Kathy

    Tourette Syndrome has a history of being misdiagnosed or undiagnosed due to its unusual and complex symptoms. This paper describes: the symptoms of Tourette Syndrome; its etiology; age of onset; therapeutic methods, such as drug therapy, psychotherapy, diet control, and hypnosis; educational implications; and employment prospects. Several…

  16. Nephrotic Syndrome

    MedlinePlus

    ... of removing extra fluids and waste from your blood — typically with an artificial kidney machine (dialyzer). Chronic kidney disease. Nephrotic syndrome may cause your kidneys to gradually lose their function over time. If kidney ... in your urine. Blood tests. If you have nephrotic syndrome, a blood ...

  17. Linburg syndrome

    PubMed Central

    Rennie, William R.J.; Muller, Hellmuth

    1998-01-01

    Objective To review the causes and demographics of Linburg syndrome. Design An illustrative case report and a demographic study. Setting Adult and pediatric orthopedic clinics at the Health Sciences Centre in Winnipeg. Patients One patient with Linburg syndrome and 200 patients and relatives presenting to adult and pediatric orthopedic clinics with conditions not involving their hands, wrists or forearms. Outcome measures The presence of the intertendinous anomaly and of carpal tunnel syndrome. Results Tendinous connection(s) between flexor pollicis longus and flexor digitorum profundus muscles were found in 20% of the study population. The anomaly was found in all age groups. No association was found between Linburg syndrome and the presence of carpal tunnel syndrome or previous injury to the hand or forearm. Conclusion Tendinous connection between flexor pollicis longus and flexor digitorum profundus muscles is a common anomaly that rarely causes clinical symptoms. PMID:9711164

  18. Syndromic craniosynostosis.

    PubMed

    Derderian, Christopher; Seaward, James

    2012-05-01

    Although most cases of craniosynostosis are nonsyndromic, craniosynostosis is known to occur in conjunction with other anomalies in well-defined patterns that make up clinically recognized syndromes. Patients with syndromic craniosynostoses are much more complicated to care for, requiring a multidisciplinary approach to address all of their needs effectively. This review describes the most common craniosynostosis syndromes, their characteristic features and syndrome-specific functional issues, and new modalities utilized in their management. General principles including skull development, the risk of developing increased intracranial pressure in craniosynostosis syndromes, and techniques to measure intracranial pressure are discussed. Evolving techniques of the established operative management of craniosynostosis are discussed together with more recent techniques including spring cranioplasty and posterior cranial vault distraction osteogenesis.

  19. Escobar syndrome mimicing congenital patellar syndrome.

    PubMed

    Ezirmik, Naci; Yildiz, Kadri; Can, Cahit Emre

    2012-08-01

    Multiple pterygium syndrome (MPS) is a syndrome that is characterized abnormal face, short length and skin pterygiums on some body legions (servical, antecubital, popliteal, interdigital and on neck). It is also called as Pterygium Colli syndrome, Escobar syndrome or Pterygium syndrome. Escobar (multyple pterygium) syndrome is a rare syndrome. Intrauterin growth reterdation, abnormal face, wide-spead pterygiums that resulted in joint contractures, ptosis, chryptoorchidism, patellar dysplasia and foot deformities are seen on this syndrome. Primarly autosomal resesive crossing are observed; also autosomal dominant and X-linked crossing. This case were presented as it has components of Escobar syndrome and Isolated Patellar Aplasia syndrome in same time.

  20. DRESS syndrome.

    PubMed

    Descamps, Vincent; Ranger-Rogez, Sylvie

    2014-01-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, initially recognized as a serious form of cutaneous drug adverse reaction, is now viewed as a drug-related syndrome that can cause life-threatening organ dysfunctions. Characteristic features include a long time interval from first drug exposure to symptom onset and a prolonged course, often with flares, even after discontinuation of the causal drug. The pathophysiology of DRESS syndrome remains incompletely understood but involves reactivation of herpes viruses (HHV-6, HHV-7, EBV, and CMV), against which the body mounts a strong immune response. The culprit drugs may not only affect epigenetic control mechanisms, thereby promoting viral reactivation, but also induce an antiviral T-cell response by interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a potentially life-threatening form of cutaneous drug adverse reaction. The severity of this syndrome is related to the systemic manifestations, which can result in multiorgan failure. DRESS syndrome is characterized by highly specific features, most notably regarding the timing of the manifestations. New insights into the underlying pathophysiological mechanisms indicate a role for immunogenetic susceptibility factors and for reactivation of human herpes viruses (HHVs), chiefly HHV-6. We report a typical case of DRESS syndrome and discuss recent data about this condition. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  1. [HELLP syndrome].

    PubMed

    Vigil-De Gracia, Paulino

    2015-01-01

    Hypertensive disorders of pregnancy are one of the most common complications of pregnancy, but one of the most serious expressions of this pathology is HELLP syndrome. The HELLP syndrome is characterized by the presence of hypertension disorder more a triad: microangiopathic hemolysis, elevated liver enzymes and low platelet count. Patient with HELLP syndrome is associated with increased maternal risk complications such as: cerebral hemorrhage, retinal detachment, hematoma/ hepatic rupture, acute renal failure, disseminated intravascular coagulation, placental abruption and therefore a maternal death. For all these reasons it is recommended to search for findings of HELLP syndrome in patients with hypertensive disorder of pregnancy. The main clinical confusion of HELLP syndrome is acute fatty liver of pregnancy, however there are parameters that help correct identification. The presence of HELLP syndrome involves a rapid termination of pregnancy and the administration of corticosteroids does not improve maternal morbidity and mortality but may help raise the platelet count, thus decreasing the need for transfusion and shorten hospital stay. Much of the decline in maternal morbidity and mortality associated with hypertensive disorders of pregnancy is in proper diagnosis and effective management of HELLP syndrome.

  2. Mass-transport deposit and mélange formation in the Ligurian accretionary complex (NW-Italy) via mutual interactions of tectonic, sedimentary and diapiric processes

    NASA Astrophysics Data System (ADS)

    Festa, A.; Codegone, G.; Dilek, Y.; Ogata, K.; Pini, G.

    2011-12-01

    Slope instability and material removal from the overriding plate are common in frontal wedges of subduction-accretionary complexes, form mass-transport deposits (MTDs), and play an important role in controlling the internal dynamics of a critical taper Coulomb wedge and its slope instability. We present different examples of ancient MTDs emplaced during the late Cretaceous-Miocene evolution of the External Ligurian accretionary wedge and the related wedge-top basins (Epiligurian Units Auct.) in the NW-Apennines, Italy. These MTDs consist of sedimentary mélanges or olistostromes and display heterogeneous deformation controlled by the degree of sediment consolidation and the velocity of gravitational processes (Festa et al., 2010 IGR; Pini et al., 2011 Springer Book). Decimeter- to meter-thick shear zones associated with localized visco-plastic deformation and highly disturbed rounded and/or subangular blocks randomly distributed in a brecciated matrix form the two end-members of structures. Crosscutting relationships between MTDs and coherent successions, tectonic mélanges - broken formation and injection bodies (shaly-dykes and/or diapirs) allow us to document their time-progressive development, the correlation with tectonic and diapiric processes, and the material redistribution forming polygenic mélanges in the frontal part of the External Ligurian accretionary wedge. Out-of-sequence "megathrust" and strike-slip faulting, fluid overpressure, presence of low-permeable layers and methane-rich fluid circulation in the sedimentary column were the main factors that controlled the emplacement of various MTDs. In all the examples described, mass-transport was closely associated and had mutual interactions with tectonic and diapiric processes (Festa, 2011 GSA Sp Publ). Tectonics played the most prominent role (directly and indirectly), whereas fluid flow and overpressure strongly controlled the mechanical behavior of sediments and facilitated the emplacement of

  3. The role of subduction channel mélanges and convergent subduction systems in the petrogenesis of post-collisional K-rich mafic magmatism in NW Tibet

    NASA Astrophysics Data System (ADS)

    Guo, Zhengfu; Wilson, Marjorie; Zhang, Lihong; Zhang, Maoliang; Cheng, Zhihui; Liu, Jiaqi

    2014-06-01

    Post-collisional potassium-rich mafic magmatism occurred in the northwestern part of the Tibetan Plateau, close to the western syntaxis of the Himalayan orogen, from 8.3 Ma to the present. This magmatism is associated with a tectonic setting influenced by opposing N and S dipping subduction systems formed during the collision of India and Asia. It postdates continent-continent collision and has been linked to the onset of near vertical subduction of Indian continental lithosphere at ~ 8 Ma. The magmatic rocks have relatively high MgO (4.02-9.04 wt.%), SiO2 (46.15-57.49 wt.%), K2O (3.26-7.23 wt.%), Ba (1071-3210 ppm), Th (8.2-85.2 ppm), and Pb (18.6-54.8 ppm) contents, and relatively low Al2O3 (12.74-15.78 wt.%). Sr-Nd-Pb isotopic compositions range from: (87Sr/86Sr)i (0.7072-0.7131), (143Nd/144Nd)i (0.511953-0.512528) and (206Pb/204Pb)i (18.67-19.08). Chondrite-normalized rare earth element (REE) patterns are characterized by light REE (LREE) enrichment, flat heavy REE (HREE) patterns and slightly negative Eu anomalies in some of the magmatic rocks. Primitive mantle-normalized incompatible element patterns display strong enrichments in large ion lithophile elements (LILE) relative to high field strength elements (HFSE) and distinct negative Ta-Nb-Ti anomalies. The major and trace element and Sr-Nd-Pb isotope characteristics of the most primitive mafic igneous rocks are interpreted in terms of a mantle source region dominated by subduction channel-derived mélange material derived from both the Indian and Asian subduction systems. This mélange material was underplated below the lithosphere of the Songpan-Ganzi terrane of NW Tibet, probably within the past 25 Ma. Partial melting of the underplated mélange was induced by adiabatic decompression linked to the onset of near vertical subduction of the Indian slab at ~ 8 Ma.

  4. Exotic ingredients in the mélange at Port Macquarie, southern New England Orogen, reveal a spicy history of crustal kneading along eastern Gondwana

    NASA Astrophysics Data System (ADS)

    Buckman, S.; Nutman, A.

    2013-12-01

    An exotic assemblage of Paleozoic subduction complex rocks occurs within the serpentinite mélange at Port Macquarie in the southern New England Orogen, eastern Australia. New U-Pb zircon dating of key components within the mélange reveals surprising results that require a complete re-evaluation of the tectonic evolution of the New England Orogen. The Rocky Beach eclogite contains detrital igneous zircon populations of Carboniferous and Permo-Triassic age which contradict previous Ordovician K-Ar ages. The Tacking Point gabbro was thought to represent a Permian intrusive equivalent to the Clarence River suite but is Devonian (390×7 Ma). Volcaniclastic sandstones of the Watonga Formation yielded 452×10 Ma igneous zircons confirming previous Ordovician conodont ages. However, volaniclastic sandstones structurally below the serpentinite melange contain volcanic/detrital zircons as young as 335 Ma that were derived from a Carboniferous arc. Post-serpentinite mafic-felsic dykes were emplaced into the mélange at ~250 Ma. We suggest that the eastern margin of Gondwana underwent episodic, thin-skinned island-arc collisions paired with widespread deformation events (e.g. Macquarie Arc - Benambran Orogeny; Gamilaroi terrane - Kanimblan Orogeny; and Gympie terrane - Hunter Bowen Orogeny). These arc collisions are followed by subduction flips that lead to periods of continental margin 'Andean-type' magmatism and accretion marked by the voluminous intrusion of S- and I-type granites. Oroclinal bending has been proposed by some to explain the overall northward displacement of the Port Macquarie serpentinite relative to the Peel Fault to the west. We introduce a new hypothesis to explain apparent oroclines within the New England Orogen involving vertical rather than lateral displacements. We propose that the Hunter-Bowen compressional event is responsible for exhuming portions of the Gamilaroi + Djungati terranes from under their Carboniferous carapace. Thus, the northward

  5. A Comparison of Documentary Approaches: Margaret Bourke-White and Erskine Caldwell, Authors of "You Have Seen Their Faces," and Dorothea Lange and Paul S. Taylor, Authors of "An American Exodus."

    ERIC Educational Resources Information Center

    Hanson, Art

    Two books that use documentary photography to examine social problems--"You Have Seen Their Faces," a 1937 study of Southern sharecroppers by Margaret Bourke-White and Erskine Caldwell, and "An American Exodus," a 1939 examination of the migration of farm families by Dorothea Lange and Paul S. Taylor--are compared in this…

  6. A Comparison of Documentary Approaches: Margaret Bourke-White and Erskine Caldwell, Authors of "You Have Seen Their Faces," and Dorothea Lange and Paul S. Taylor, Authors of "An American Exodus."

    ERIC Educational Resources Information Center

    Hanson, Art

    Two books that use documentary photography to examine social problems--"You Have Seen Their Faces," a 1937 study of Southern sharecroppers by Margaret Bourke-White and Erskine Caldwell, and "An American Exodus," a 1939 examination of the migration of farm families by Dorothea Lange and Paul S. Taylor--are compared in this…

  7. The Travails of Criticality: Understanding Peter McLaren's Revolutionary Vocation. An Article Review of Peter McLaren, "Pedagogy of Insurrection" (New York: Peter Lang, 2015)

    ERIC Educational Resources Information Center

    Baldacchino, John

    2017-01-01

    This is an article review of Peter McLaren's "Pedagogy of Insurrection" (New York: Peter Lang, 2015). While it seeks to position McLaren's work within the context of critical pedagogy, this paper also assesses McLaren from the wider discussion of Marxist--Hegelian discourse as it evolved within the Left. Engaging with McLaren critically,…

  8. Hubris syndrome.

    PubMed

    Owen, David

    2008-08-01

    Hubris syndrome is associated with power, more likely to manifest itself the longer the person exercises power and the greater the power they exercise. A syndrome not to be applied to anyone with existing mental illness or brain damage. Usually symptoms abate when the person no longer exercises power. It is less likely to develop in people who retain a personal modesty, remain open to criticism, have a degree of cynicism or well developed sense of humour. Four heads of government in the last 100 years are singled out as having developed hubris syndrome: David Lloyd George, Margaret Thatcher, George W Bush and Tony Blair.

  9. [DRESS syndrome].

    PubMed

    Adamcová, Monika; Šturdík, Igor; Koller, Tomáš; Payer, Juraj

    2016-04-01

    DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is severe drug-induced allergic-type reaction which occurs few days to weeks after taking a drug in a predisposed patient. Organ damage, eosinophilia and skin rash are typical at presentation. Corticotherapy is often necessary in severe cases. In this report we describe a case of 56-year old female with fever, elevated liver tests and skin rash. DRESS syndrome was diagnosed and allopurinol was indentified as a causative drug. Due to possible fatal outcome, DRESS syndrome should be considered in a differential diagnosis of all patients presenting with similar signs and symptoms.

  10. Jerusalem syndrome.

    PubMed

    Bar-el, Y; Durst, R; Katz, G; Zislin, J; Strauss, Z; Knobler, H Y

    2000-01-01

    Jerusalem's psychiatrists expect to encounter, as the millennium approaches, an ever-increasing number of tourists who, upon arriving in Jerusalem, may suffer psychotic decompensation. To describe the Jerusalem syndrome as a unique acute psychotic state. This analysis is based on accumulated clinical experience and phenomenological data consisting of cultural and religious perspectives. Three main categories of the syndrome are identified and described, with special focus on the category pertaining to spontaneous manifestations, unconfounded by previous psychotic history or psychopathology. The discrete form of the Jerusalem syndrome is related to religious excitement induced by proximity to the holy places of Jerusalem, and is indicated by seven characteristic sequential stages.

  11. Rapunzel syndrome

    PubMed Central

    Altonbary, Ahmed Youssef; Bahgat, Monir Hussein

    2015-01-01

    Bezoars are concretions of human or vegetable fibers that accumulate in the gastrointestinal tract. Trichobezoars are common in patients with underlying psychiatric disorders who chew and swallow their own hair. Rapunzel syndrome is a rare form of gastric trichobezoar with a long tail extending into the small bowel. This syndrome was first described in 1968 by Vaughan et al. and since then till date just 64 cases have been described in the literature. We present the only documented case with Rapunzel syndrome in Egypt. PMID:27847892

  12. Neuroacanthocytosis syndromes.

    PubMed

    Jung, Hans H; Danek, Adrian; Walker, Ruth H

    2011-10-25

    Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome which have a Huntington's disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's disease-like 2, autosomal recessive pantothenate kinase-associated neurodegeneration and several inherited disorders of lipoprotein metabolism, namely abetalipoproteinemia (Bassen-Kornzweig syndrome) and hypobetalipoproteinemia leading to vitamin E malabsorption. The latter disorders are characterized by a peripheral neuropathy and sensory ataxia due to dorsal column degeneration, but movement disorders and cognitive impairment are not present. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway. Laboratory tests include blood smears to detect acanthocytosis and determination of serum creatine kinase. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent in McLeod syndrome. Western blot for chorein demonstrates absence of this protein in red blood cells of chorea-acanthocytosis patients. Specific genetic testing is possible in all NA syndromes. Differential diagnoses

  13. Gerstmann's syndrome.

    PubMed

    Benton, A L

    1992-05-01

    Recent case reports describe the occurrence of a more or less pure Gerstmann syndrome in association with a focal lesion in the posterior perisylvian territory of the brain's left hemisphere. In addition, an electrocortical stimulation study reported the Gerstmann symptom combination and a number of other symptom combinations on stimulation of small areas in the left posterior parietotemporal cortex. The neuropsychological implications of these and other recent findings are considered in light of the variety of "syndromes" produced by lesions in this region, the rare occurrence of Gerstmann's syndrome, and its appearance as a consequence of lesions in diverse cerebral areas.

  14. [Autoinflammatory syndromes/fever syndromes].

    PubMed

    Schedel, J; Bach, B; Kümmerle-Deschner, J B; Kötter, I

    2011-05-01

    Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), "pyogenic arthritis, acne, pyoderma gangrenosum" (PAPA), and "pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1β. In "early-onset of enterocolitis (IBD)", a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn's disease also are mentioned.

  15. First Preliminary Report on Isolation and Characterization of Novel Acinetobacter spp. in Casing Soil Used for Cultivation of Button Mushroom, Agaricus bisporus (Lange) Imbach.

    PubMed

    Choudhary, D K

    2011-01-01

    Despite evaluation of large number of agroindustrial wastes for their use as casing material for Agaricus bisporus (Lange) Imbach cultivation, scant attention has been given to the importance of biological properties of casing materials. In the present study, an attempt was made to characterize the bacterial flora in casing layer, namely, Farm Yard Manure (FYM) and Spent Mushroom Substrate/spent compost (SMS/SC) (FYM+SC, 3 : 1) and FYM and Vermi Compost (VC) (FYM+VC, 3 : 1), employing partial 16S rDNA sequencing. Available data showed a significant variety of organisms that included Acinetobacter and Pseudomonas of the γ-proteobacteria, that were the most frequently encountered genera. This is the first preliminary report on the microbial diversity of casing soils and demonstrates the presence of Acinetobacter spp. that has not been previously described in casing material.

  16. First Preliminary Report on Isolation and Characterization of Novel Acinetobacter spp. in Casing Soil Used for Cultivation of Button Mushroom, Agaricus bisporus (Lange) Imbach

    PubMed Central

    Choudhary, D. K.

    2011-01-01

    Despite evaluation of large number of agroindustrial wastes for their use as casing material for Agaricus bisporus (Lange) Imbach cultivation, scant attention has been given to the importance of biological properties of casing materials. In the present study, an attempt was made to characterize the bacterial flora in casing layer, namely, Farm Yard Manure (FYM) and Spent Mushroom Substrate/spent compost (SMS/SC) (FYM+SC, 3 : 1) and FYM and Vermi Compost (VC) (FYM+VC, 3 : 1), employing partial 16S rDNA sequencing. Available data showed a significant variety of organisms that included Acinetobacter and Pseudomonas of the γ-proteobacteria, that were the most frequently encountered genera. This is the first preliminary report on the microbial diversity of casing soils and demonstrates the presence of Acinetobacter spp. that has not been previously described in casing material. PMID:22007222

  17. Ultra-oxidized rocks in subduction mélanges? Decoupling between oxygen fugacity and oxygen availability in a Mn-rich metasomatic environment

    NASA Astrophysics Data System (ADS)

    Tumiati, Simone; Godard, Gaston; Martin, Silvana; Malaspina, Nadia; Poli, Stefano

    2015-06-01

    The manganese ore of Praborna (Italian Western Alps) is embedded within a metasedimentary sequence belonging to a subduction mélange equilibrated at high-pressure (HP) conditions (ca. 2 GPa) during the Alpine orogenesis. The pervasive veining of the ore and the growth of "pegmatoid" HP minerals suggest that these Mn-rich rocks strongly interacted with slab-derived fluids during HP metamorphism. These rocks are in textural and chemical equilibrium with the veins and in contact with sulphide- and magnetite-bearing metabasites at the bottom of the sequence. They contain braunite (Mn2+Mn3+6SiO12), quartz, pyroxmangite (Mn2+SiO3), and minor hematite, omphacite, piemontite and spessartine-rich garnet. Sulphides are absent in the Mn-rich rocks, whereas sulphates (barite, celestine) occur together with As- and Sb-oxides and silicates. This rock association provides an excellent natural laboratory to constrain the redox conditions in subducting oceanic slab mélanges at HP and fluid-present conditions. Similarly to Fe-bearing minerals, Mn oxides and silicates can be regarded as natural redox-sensors. A thermodynamic dataset for these Mn-bearing minerals is built, using literature data as well as new thermal expansion parameters for braunite aud pyrolusite, derived from experiments. Based on this dataset and the observed assemblages at Praborna, thermodynamic calculations show that these mélange rocks are characterised by ultra-oxidized conditions (∆FMQ up to + 12.7) if the chemical potential of oxygen (or the oxygen fugacity fO2) is accounted for. On the other hand, if the molar quantity of oxygen is used as the independent state variable to quantify the bulk oxidation state, the ore appears only moderately oxidized and comparable to typical subduction-slab mafic eclogites. Such an apparent contradiction may happen in rock systems whenever oxygen is improperly considered as a perfectly mobile component. In the Earth's mantle, redox reactions take place mainly between

  18. Joubert Syndrome

    MedlinePlus

    ... Synapses, & Circuits Health Administrator Division of Intramural Research, Scientific Director ... This research is critical for increasing our understanding of Joubert syndrome, and for developing methods of treatment and prevention. NINDS, in conjunction with ...

  19. Rett Syndrome

    MedlinePlus

    ... for slowed growth and development, but your daily observations are very important. Any medications that your child ... your child's symptoms? Diagnosing Rett syndrome involves careful observation of your child's growth and development and answering ...

  20. Horner Syndrome

    MedlinePlus

    ... birth Tumor of the hormonal and nervous systems (neuroblastoma) Unknown causes In some cases the cause of ... a tumor of the hormonal and nervous systems (neuroblastoma). There's no specific treatment for Horner syndrome. Often, ...

  1. Behcet's Syndrome

    MedlinePlus

    Behcet's syndrome is a disease that involves vasculitis, which is inflammation of the blood vessels. It causes problems in many parts of the body. The ... National Institute of Arthritis and Musculoskeletal and Skin Diseases

  2. Metabolic Syndrome

    MedlinePlus

    ... cause of metabolic syndrome. The cause might be insulin resistance. Insulin is a hormone your body produces to help ... into energy for your body. If you are insulin resistant, too much sugar builds up in your ...

  3. Menkes syndrome

    MedlinePlus

    ... Menkes syndrome, cells in the body can absorb copper, but they are unable to release it. It ... makes it hard for the body to distribute copper in food from the intestines into the bloodstream ...

  4. Klinefelter syndrome

    MedlinePlus

    Testosterone therapy may be prescribed. This can help: Grow body hair Improve appearance of muscles Improve concentration Improve mood and self esteem Increase energy and sex drive Increase strength Most men with this syndrome are not able to get ...

  5. Gerstmann's Syndrome

    MedlinePlus

    ... It is characterized by four primary symptoms: a writing disability (agraphia or dysgraphia), a lack of understanding ... speaking, in understanding speech, or in reading and writing). There are few reports of the syndrome, sometimes ...

  6. Marfan syndrome

    PubMed Central

    Jain, Eesha; Pandey, Ramesh Kumar

    2013-01-01

    Marfan syndrome is a rare autosomal dominant disorder of the connective tissue, with skeletal, ligamentous, orooculofacial, pulmonary, abdominal, neurological and the most fatal, cardiovascular manifestations. It has no cure but early diagnosis, regular monitoring and preventive lifestyle regimen ensure a good prognosis. However, the diagnosis can be difficult as it is essentially a clinical one, relying on family history, meticulous physical examination and investigation of involved organ systems. Patients of Marfan syndrome portray very typical physical and orofacial characteristics, suggesting obvious recognition, but due to variable phenotypic expression, cases often go unnoticed unless a full range of attributing features is apparent. Dental practitioners are very likely to encounter patients of Marfan syndrome at an early age as they frequently present for dental treatment. The present case report illustrates the preliminary screening of Marfan syndrome in a dental office followed by timely diagnosis and appropriate referrals. PMID:24336584

  7. Scheie syndrome

    MedlinePlus

    ... to have children and who have a family history of Scheie syndrome. Counseling is also recommended for families who ... L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap ...

  8. Sanfilippo syndrome

    MedlinePlus

    ... to have children and who have a family history of Sanfilippo syndrome. Counseling is also recommended for ... L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap ...

  9. Beals Syndrome

    MedlinePlus

    ... have many of the skeletal (bone) and aortic enlargement problems as people with Marfan syndrome, and treatments ... appearance to the top of the ear Aortic enlargement and/or mitral valve regurgitation (occasionally) People with ...

  10. Reye Syndrome

    MedlinePlus

    ... Browse Related Terms Pediatric Liver Disease , Reye Syndrome , Aspirin , Progression of Liver Disease , Liver Transplant Help Fight ... a mystery. However studies have shown that using aspirin to treat viral illnesses increases the risk of ...

  11. Caplan syndrome

    MedlinePlus

    ... people with rheumatoid arthritis who have breathed in mining dust that contains coal. This lung disease is ... Caplan syndrome is caused by breathing in coal mining dust. This causes inflammation and can lead to ...

  12. HELLP syndrome

    MedlinePlus

    ... It is considered to be a variant of preeclampsia. Sometimes the presence of HELLP syndrome is due ... out of 1,000 pregnancies. In women with preeclampsia or eclampsia , the condition develops in 10% to ...

  13. Cushing's Syndrome

    MedlinePlus

    ... cause is long-term exposure to too much cortisol, a hormone that your adrenal gland makes. Sometimes, ... can cause your body to make too much cortisol. Cushing's syndrome is rare. Some symptoms are Upper ...

  14. Eisenmenger syndrome

    MedlinePlus

    ... in some people who were born with structural problems of the heart. Causes Eisenmenger syndrome is a condition that results from abnormal blood circulation caused by a defect in the heart. Most ...

  15. Brugada Syndrome

    MedlinePlus

    ... you suspect it may be because of a heart condition, seek emergency medical attention. If your parent, sibling or child ... especially in children. Complications of Brugada syndrome require emergency ... loss of heart function, breathing and consciousness, which often occurs while ...

  16. Morquio syndrome

    MedlinePlus

    ... chap 40. Read More Autosomal recessive Enzyme Heart failure - overview Sanfilippo syndrome Short stature Review Date 4/20/2015 Updated by: Chad Haldeman-Englert, MD, FACMG, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical ...

  17. Piriformis syndrome

    MedlinePlus

    ... the sciatic nerve. The syndrome, which affects more women than men, is uncommon. But when it occurs, it can cause sciatica . Causes The piriformis muscle is involved in nearly every movement you make with your lower body, from walking ...

  18. Tourette syndrome

    MedlinePlus

    ... medicines are available to treat Tourette syndrome. The exact medicine that is used depends on the symptoms ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

  19. Reifenstein syndrome

    MedlinePlus

    ... syndrome Images Male reproductive system References Achermann JC, Hughes IA. Pediatric disorders of sex development. In: Melmed S, ... Birmingham, Birminghum, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla ...

  20. Hunter Syndrome

    MedlinePlus

    ... normal or near-normal height. Hernias (inguinal and umbilical) are common in Hunter syndrome. A hernia occurs ... in which the membranes that surround the spinal cord may become thick and scarred (hypertrophic cervical pachymeningitis). ...

  1. [Heptopulmonary syndrome].

    PubMed

    Cuadrado, Antonio; Díaz, Ainhoa; Iruzubieta, Paula; Salcines, José Ramón; Crespo, Javier

    2015-01-01

    Hepatopulmonary syndrome is characterized by the presence of liver disease, pulmonary vascular dilatations, and arterial hypoxemia. It is usually associated with cirrhosis of any origin, but has been described in other liver diseases, both acute and chronic, and not always associated with portal hypertension. The gold standard method to detect pulmonary vascular dilations is contrast enhancement echocardiography with saline and is essential for the diagnosis of hepatopulmonary syndrome. These dilatations reflect changes in the pulmonary microvasculature (vasodilatation, intravascular monocyte accumulation, and angiogenesis) and induce a ventilation/perfusion mismatch, or even true intrapulmonary shunts, which eventually trigger hypoxemia. This syndrome worsens patients' prognosis and impairs their quality of life and may lead to the need for liver transplantation, which is the only effective and definitive treatment. In this article, we review the etiological, pathophysiological, clinical and therapeutic features of this syndrome. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  2. Gilbert's Syndrome

    MedlinePlus

    ... causes Gilbert's syndrome. The gene normally controls an enzyme that helps break down bilirubin in your liver. ... your bloodstream to the liver, where normally an enzyme breaks down the bilirubin and removes it from ...

  3. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? In the more severely affected cases of Brown ... acquired and congenital cases. In congenital cases, the eye movement problem is usually constant and unlikely to resolve ...

  4. Fahr's Syndrome

    MedlinePlus

    ... Understanding Sleep The Life and Death of a Neuron Order Publications Support Resources Patient Organizations Professional Societies ... Myopathy Information Page Moebius Syndrome Information Page Motor Neuron Diseases Information Page Moyamoya Disease Information Page Mucolipidoses ...

  5. Dravet Syndrome

    MedlinePlus

    ... Research Research at NINDS Focus on Research Bioengineering Epilepsy Health Disparities Neural Interfaces Parkinson's Disease Spinal Cord ... basic and clinical research on all types of epilepsy, including Dravet syndrome. Study of the genetic defects ...

  6. Dressler's Syndrome

    MedlinePlus

    ... syndrome can cause more-serious complications, including: Cardiac tamponade. Inflammation of the pericardium can cause fluids to ... including: Draining excess fluids. If you develop cardiac tamponade, your doctor will likely recommend a procedure (pericardiocentesis) ...

  7. Hunter syndrome

    MedlinePlus

    Hunter syndrome is a disease in which long chains of sugar molecules (glycosaminoglycans, formerly called mucopolysaccharides ) are ... of the enzyme iduronate sulfatase. Without this enzyme, chains of sugar molecules build up in various body ...

  8. 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 — ...

  9. Cushing syndrome

    MedlinePlus

    ... with Cushing syndrome have: Round, red, full face ( moon face ) Slow growth rate (in children) Weight gain ... constitute endorsements of those other sites. Copyright 1997-2017, A.D.A.M., Inc. Duplication for commercial ...

  10. [Mobius syndrome].

    PubMed

    Vladuţiu, Cristina; Duma, Ionela

    2012-01-01

    Mobius syndrom, an anomaly in cranial nerve developement, presents with a remarkable clinical polymorphism. The rare occurence of this pathology and the questions raised by the diagnosis and treatment determined us to make this presentation.

  11. Autoinflammatory syndromes.

    PubMed

    Galeazzi, M; Gasbarrini, G; Ghirardello, A; Grandemange, S; Hoffman, H M; Manna, R; Podswiadek, M; Punzi, L; Sebastiani, G D; Touitou, I; Doria, A

    2006-01-01

    The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

  12. Aase syndrome

    MedlinePlus

    Aase-Smith syndrome; Hypoplastic anemia - triphalangeal thumbs, Aase-Smith type ... Jones KL, Jones MC, Del Campo M, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, ...

  13. Down Syndrome

    MedlinePlus

    ... can help improve skills. They may include speech, physical, occupational, and/or educational therapy. With support and treatment, many people with Down syndrome live happy, productive lives. NIH: National Institute of Child Health and Human Development

  14. Turner Syndrome

    MedlinePlus

    ... turnersyndrome. html • Eunice Kennedy Shriver National Institutes of Child Health & Human Development (NIH): www. nichd. nih. gov/ health/ topics/ Turner_ Syndrome. cfm • Mayo Clinic: www. mayoclinic. com/ health/ turner- ...

  15. Reye syndrome

    MedlinePlus

    ... e1-1104.e1. Hurwitz ES. Reye's syndrome. In: Cherry JD, Demmler-Harrison G, Kaplan SL, Steinblach W, Hotez P, eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases . 7th ed. Philadelphia, ...

  16. Duane Syndrome

    MedlinePlus

    ... due to abnormal development of the 6 th cranial nerve. It is characterized by difficulty rotating one or ... eye muscles. In Duane syndrome, the 6 th cranial nerve that controls the lateral rectus muscle (the muscle ...

  17. Noonan syndrome.

    PubMed

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2013-01-26

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS-MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype-phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

  18. Noonan syndrome

    PubMed Central

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2014-01-01

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

  19. [HELLP syndrome].

    PubMed

    Filipowicz, Ewa; Staszków, Monika

    2015-01-01

    HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) is a relatively rare complication of pregnancy. It usually develops in the IIId trimester or after delivery. HELLP syndrome is associated with increased maternal (placental abruption, disseminated intravascular coagulation, hepatic hematomas and rupture, and acute kidney injury) and neonatal (prematurity, low birth weight) risk complications. In this article the diagnosis, clinical picture and treatment of this disease have been shortly reviewed.

  20. SAPHO syndrome.

    PubMed

    Carneiro, Sueli; Sampaio-Barros, Percival D

    2013-05-01

    SAPHO syndrome is a disorder characterized by Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis. As the osteoarticular and skin manifestations often do not occur simultaneously and there are no validated diagnostic criteria, the diagnosis can be difficult. Clinical and imaging investigation is necessary to establish the many differential diagnoses of SAPHO syndrome. The etiopathogenesis involves infectious (probably Propionibacterium acnes), immunologic, and genetic factors. Treatment is based on information gathered from case reports and small series, and is related to specific skin or articular symptoms.

  1. Mass transport-related stratal disruption within sedimentary mélanges: Examples from the northern Apennines (Italy) and south-central Pyrenees (Spain)

    NASA Astrophysics Data System (ADS)

    Ogata, Kei; Mutti, Emiliano; Pini, Gian Andrea; Tinterri, Roberto

    2012-09-01

    We report here mass transport-related disruption processes and their artifacts within sedimentary mélanges. The case studies include the early Oligocene wedge-top mass transport deposits in the northern Apennines (Italy) and the Eocene foredeep carbonate megabreccias from the south-central Pyrenees (Spain). These "chaotic" units commonly share a block-in-matrix fabric expressed by variously deformed slide blocks of different size, lithology, age and shape, embedded in a fine-grained matrix. Geophysical studies of modern continental margins have characterized many of these deposits, which, however, remain still relatively poorly described in term of meso-scale characteristics. The prominent feature of the analyzed mass transport deposits is the occurrence of an unsorted, strongly mixed, relatively fine-grained clastic matrix, infilling space between large clasts and blocks. This matrix shows either fluidal structures related to simple shear, or a structureless, homogeneous fabric, both probably related to liquefaction/fluidization processes and thus, to the internal strength of the mixed lithologies. We interpreted this phase as a liquefied mixture of water and sediment, characterized by high mobility due to overpressured conditions, as evidenced by both lateral and vertical injections. On a much larger scale this kind of matrix could represent the acoustically "transparent" facies separating slide blocks of many seismic examples. The inferred generating mechanism is that of a progressive soft sediment deformation, linked to different phases of submarine landslide evolution (i.e. failure, translation, accumulation and post-depositional stages), leading to an almost complete stratal disruption of involved bedded sequences, either within the slide mass and in the underlying substrate. In this framework the down-slope movement is favored by the development of ductile, overpressured shear zones, both internally and along the basal sliding horizon. Therefore, this

  2. Timing of subduction and exhumation in a subduction channel: Evidence from slab melts from La Corea Mélange (eastern Cuba)

    NASA Astrophysics Data System (ADS)

    Blanco-Quintero, I. F.; Rojas-Agramonte, Y.; García-Casco, A.; Kröner, A.; Mertz, D. F.; Lázaro, C.; Blanco-Moreno, J.; Renne, P. R.

    2011-11-01

    High pressure igneous rocks (tonalites), generated by partial melting of subducted basaltic rocks accreted to the mantle wedge, are present in the La Corea serpentinite-matrix mélange (eastern Cuba) as centimeter- to meter-sized blocks and as concordant to crosscutting veins within high-pressure parent amphibolite blocks. The slab melts have adakitic signatures, in agreement with formation after partial melting of metabasite. Thermobarometric calculations indicate 620-680 °C and 13-15 kbar during crystallization of tonalites and down to 250-300 °C, 6 kbar during retrogression, indicating counter-clockwise P-T paths (hot subduction-cool exhumation). Free water required for melting of amphibolite at moderate temperature (700-750 °C) and moderate pressure (13-16 kbar) close to the wet basaltic solidus is inferred to have been provided after dehydration of sediments, altered basaltic crust and serpentinite of the subducting Proto-Caribbean lithosphere. Single zircon (SHRIMP) and phengite 40Ar/39Ar age data constrain the P-T-t evolution of the mélange from the timing of crystallization of melts at ~ 110-105 Ma to cooling at ~ 87-84 Ma, ca. 350 °C, ca. 9 kbar. These figures are consistent with subduction of an oblique ridge, shortly before 115 Ma. Furthermore, our data indicate very slow exhumation (ca. 1 mm/yr) in the subduction channel during the oceanic convergence stage (120-70 Ma) until final fast exhumation to the surface occurred at 70-65 Ma during a regional arc-platform collision event.

  3. New insights on a metamorphosed middle-late Miocene mélange of the Yuli Belt in eastern Taiwan: Evidence from Zircon U-Pb dating

    NASA Astrophysics Data System (ADS)

    Chen, W. S.; Chung, S. L.; Chou, H. Y.; Lee, Y. H.

    2016-12-01

    The Yuli Metamorphic Belt has been the topic of petrological and radiochronological studies for over 40 years, and was interpreted as a Mesozoic mélange, because the protolith ages of metamorphic rock have difficult to determine due to a lack of age information from higher closure temperature minerals by radiometric dating. This study focuses on zircon U-Pb dating for schist and exotic blueschist blocks in order to constrain the depositional age of the Yuli Belt. Several essential distinctions in detrital zircon U-Pb age distributions are recognized for 14 siliceous schists of mélange-hosted rocks that are similar in age population to the Cretaceous, Eocene-Oligocene, and Miocene strata in Taiwan. It appears to be associated with sedimentary fragments of various ages which seem to represent a chaotic mixture of sediments. Three blueschists of a volcanic-arc protolith enclosed within the host rocks obtain crystallization ages of 15.4±0.4, 15.5±0.3, and 16.0±0.2 Ma by zircon U-Pb dating. In consideration of the available data regarding the Cretaceous-Miocene host rocks and middle Miocene exotic blocks, it strongly supports that the Yuli Belt represents an accretionary complex to occur at least after middle Miocene, and not of the Cretaceous age as is currently presented in the extant literature. Therefore, the Yuli Belt formed at deep-levels of the accretionary wedge during the South China Sea oceanic crust subduction at the middle-late Miocene. Then, the rapid uplifting of the metamorphic belt was probably caused by doubly vergent wedge extrusion due to the Pliocene arc-continent collision.

  4. [DRESS syndrome].

    PubMed

    Rabenkogo, A; Vigue, M G; Jeziorski, E

    2015-01-01

    DRESS syndrome (drug reaction eosinophilia and systemic symptoms) is a rare and serious drug toxidermia with potentially multiple organ dysfunctions. This report relates the case of a 9-year-old girl who presented a right cervical and mediastinal adenopathy with a mediastinal lump, fever, and deterioration of the general condition. The hospital assessment concluded in an abscess due to Staphylococcus aureus secreting a Panton-Valentine toxin with nonsevere pleuritis and pericarditis. The outcome was favorable with antibiotic treatment consisting of amoxicillin-acid clavulanic, amikacin, and clindamycin followed by oxacillin, rifampicin, and colchicine. On the 25th day of treatment, she presented recurrence of fever with a generalized rash, moderate hepatic cytolysis, hypereosinophilia, with the presence of activated lymphocytes that were further suggestive of visceral DRESS syndrome. A skin biopsy was performed that confirmed the diagnosis. The outcome was favorable after stopping all ongoing treatments even though none of the administered treatments were classically responsible for the syndrome. Symptomatic treatments (antihistaminic and topical steroids) were also administered. Patch tests, performed secondarily, were positive to penicillins; amoxicillin-clavulanic acid or oxacillin were then suspected of being responsible for the DRESS syndrome. Potentially serious, the DRESS syndrome should be considered together with atoxic epidermal necrolysis or Stevens-Johnson syndromes in the case of any rash appearing after drug administration, especially in the presence of face and eyelid edema. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Learning about WAGR Syndrome

    MedlinePlus

    ... children who have WAGR syndrome may have normal intelligence. Other symptoms of WAGR syndrome may also include: ... mild. Some individuals with WAGR syndrome have normal intelligence. Children with WAGR syndrome should be referred for ...

  6. What is Metabolic Syndrome?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Metabolic Syndrome? Metabolic syndrome is the name for a group of ... that may play a role in causing metabolic syndrome. Outlook Metabolic syndrome is becoming more common due to a ...

  7. Russell-Silver syndrome

    MedlinePlus

    Silver-Russell syndrome; Silver syndrome; RSS; Russell-Silver syndrome ... Organization for Rare Disorders -- rarediseases.org/rare-diseases/russell-silver-syndrome NIH/NLM Genetics Home Reference -- ghr. ...

  8. Irritable Bowel Syndrome

    MedlinePlus

    ... Want to Know About Puberty Train Your Temper Irritable Bowel Syndrome KidsHealth > For Kids > Irritable Bowel Syndrome Print A ... to minimize or prevent these symptoms. What Is Irritable Bowel Syndrome? Irritable bowel syndrome (IBS) is a fairly common ...

  9. Down Syndrome (For Kids)

    MedlinePlus

    ... CPR: A Real Lifesaver Kids Talk About: Coaches Down Syndrome KidsHealth > For Kids > Down Syndrome Print A A ... skills. continue Do a Lot of People Have Down Syndrome? Down syndrome is not contagious , so you can' ...

  10. What Is Down Syndrome?

    MedlinePlus

    ... Down Syndrome » What Is Down Syndrome? What Is Down Syndrome? In every cell in the human body there ... degrees, or not at all. How Common is Down Syndrome? According to the Centers for Disease Control and ...

  11. Preexcitation Syndromes.

    PubMed

    Bhatia, Atul; Sra, Jasbir; Akhtar, Masood

    2016-03-01

    The classic electrocardiogram in Wolff-Parkinson-White (WPW) syndrome is characterized by a short PR interval and prolonged QRS duration in the presence of sinus rhythm with initial slurring. The clinical syndrome associated with above electrocardiogram finding and the history of paroxysmal supraventricular tachycardia is referred to as Wolff-Parkinson-White syndrome. Various eponyms describing accessory or anomalous conduction pathways in addition to the normal pathway are collectively referred to as preexcitation syndromes. The latter form and associated eponyms are frequently used in literature despite controversy and disagreements over their actual anatomical existence and electrophysiological significance. This communication highlights inherent deficiencies in the knowledge that has existed since the use of such eponyms began. With the advent of curative ablation, initially surgical, and then catheter based, the knowledge gaps have been mostly filled with better delineation of the anatomic and electrophysiological properties of anomalous atrioventricular pathways. It seems reasonable, therefore, to revisit the clinical and electrophysiologic role of preexcitation syndromes in current practice.

  12. Pfeiffer syndrome.

    PubMed

    Vogels, Annick; Fryns, Jean-Pierre

    2006-06-01

    Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

  13. Sheehan's syndrome.

    PubMed

    Keleştimur, Fahrettin

    2003-01-01

    Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. It may be rarely seen without massive bleeding or after normal delivery. Improvement in obstetric care and availability of rapid blood transfusion coincided with a remarkable reduction in the frequency of Sheehan's syndrome particularly in western society. But it has recently been reported more often from well-developed countries. It is one of the most common causes of hypopituitarism in underdeveloped or developing countries. Enlargement of pituitary gland, small sella size, disseminated intravascular coagulation and autoimmunity have been suggested to play a role in the pathogenesis of Sheehan's syndrome in women who suffer from severe postpartum hemorrhage. The patients may seek medical advice because of various presentations ranging from non-specific symptoms to coma and the clinical manifestation may change from one patient to another. Failure of postpartum lactation and failure to resume menses after delivery are the most common presenting symptoms. Although a small percentage of patients with Sheehan's syndrome may cause abrupt onset severe hypopituitarism immediately after delivery, most patients have a mild disease and go undiagnosed and untreated for a long time. It may result in partial or panhypopituitarism and GH is one of the hormones lost earliest. The great majority of the patients has empty sella on CT or MRI. Lymphocytic hypophysitis should be kept in mind in differential diagnosis. In this review, the old and recent data regarding Sheehan's syndrome are presented.

  14. Video Game Vision Syndrome: A New Clinical Picture in Children?

    PubMed

    Rechichi, Caterina; De Mojà, Gilda; Aragona, Pasquale

    2017-08-29

    To examine a possible relationship between exposure to video games/electronic screens and visual issues in children between 3 and 10 years of age. An observational, cross-sectional study of a population of children using video games was employed. All patients between 3 and 10 years of age were recruited at an outpatient unit accredited by the Italian Regional Health Service. Three hundred twenty children (159 boys and 161 girls; mean age = 6.9 ± 2 years) were observed. Ophthalmological examination included assessment of stereoscopic vision on Lang-Stereotests I and II (LANG-STEREOTEST AG, Küsnacht, Switzerland) and identification of the dominant eye using the Dolman method. Furthermore, a questionnaire was used to record asthenopic symptoms and daily exposure to video games and electronic screens. Two groups of children were examined according to the average amount of time spent playing video games daily: children who played video games for less than 30 minutes per day and not every day (control group) and children who played video games for 30 minutes or more every day (video game group). Both groups were then divided into two subgroups: children using other types of electronic screens (eg, televisions, computers, tablets, and smartphones) for less than 3 hours daily (low electronic use subgroup) and children using other types of electronic screens for 3 hours or more per day (high electronic use subgroup). Asthenopia (especially headache, eyelid tic, transient diplopia, and dizziness), absence of fine stereopsis, and refractive errors were statistically more frequent (mainly in the dominant eye) of children in the video game group. These symptoms were frequent and peculiar in the video game group and might be part of a video game vision syndrome that has not been defined yet. It is important to recognize these signs as possible functional disorders to avoid erroneous diagnostic and therapeutic interventions. [J Pediatr Ophthalmol Strabismus. 201X

  15. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  16. Can Myelodysplastic Syndromes Be Prevented?

    MedlinePlus

    ... Myelodysplastic Syndromes Causes, Risk Factors, and Prevention Can Myelodysplastic Syndromes Be Prevented? Since smoking is linked to the ... Syndromes? Can Myelodysplastic Syndromes Be Prevented? More In Myelodysplastic Syndromes About Myelodysplastic Syndromes Causes, Risk Factors, and Prevention ...

  17. Apert's Syndrome

    PubMed Central

    Jyothsna, Mandapati; Ahmed, Syed Basheer; Sree Lakshmi, Ketham Reddy

    2014-01-01

    ABSTRACT Apert's syndrome (acrocephalosyndactyly) is a rare congenital disorder characterized by craniosynostosis, midfacial malforma­tion and symmetrical syndactyly of hands and feet. Craniofacial deformities include cone-shaped calvarium, fat forehead, prop-tosis, hypertelorism and short nose with a bulbous tip. Intraoral findings include high arched palate with pseudocleft, maxillary transverse and sagittal hypoplasia with concomitant dental crowding, skeletal and dental anterior open bite and several retained primary teeth. We report one such case of 14-year-old boy having all the classical features of Apert's syndrome with particular emphasis on brief review of genetic features. How to cite this article: Kumar GR, Jyothsna M, Ahmed SB, Lakshmi KRS. Apert's Syndrome. Int J Clin Pediatr Dent 2014;7(1):69-72. PMID:25206244

  18. Compartment syndromes

    NASA Technical Reports Server (NTRS)

    Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

    1989-01-01

    The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

  19. Compartment syndromes

    NASA Technical Reports Server (NTRS)

    Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

    1989-01-01

    The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

  20. Cushing syndrome.

    PubMed

    Bista, Bibek; Beck, Nancy

    2014-02-01

    Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. The most common cause of Cushing syndrome in children and adolescents is exogenous administration of glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension. Almost invariably, linear growth is severely diminished, a factor which may be useful in differentiating between childhood obesity and Cushing syndrome. Diagnostic approaches are based on distinguishing between adrenocorticotropic hormone (ACTH)-dependent and ACTH-independent etiologies, and consideration of the most likely diagnosis by age. Treatment modality is dependent upon etiology. After cure, important components of care include attention to linear growth, pubertal progression and body composition.

  1. [Autoinflammatory syndromes].

    PubMed

    Gomes, José Melo; Gomes, Sónia Melo; Conde, Marta

    2010-01-01

    Autoinflammatory syndromes (AIS) are a heterogeneous group of congenital diseases characterized by the presence of recurrent episodes of fever and local or generalized inflammation, in the absence of infectious agents, detectable auto-antibodies or antigen-specific autoreactive T-cells. These diseases have been much better understood during the past 15 years, mainly due to the marked advances of the Human Genoma Project and its implications in the identification and characterization of genetic mutations. In this paper we make a revision of the classification of AIS and focus our attention specially on the cryopyrin-associated periodic syndromes (CAPS), in particular the CINCA syndrome that shares many clinical characteristics with juvenile idiopathic arthritis.

  2. The Arkot Dağ Mélange in Araç area, central Turkey: Evidence of its origin within the geodynamic evolution of the Intra-Pontide suture zone

    NASA Astrophysics Data System (ADS)

    Göncüoglu, M. Cemal; Marroni, Michele; Pandolfi, Luca; Ellero, Alessandro; Ottria, Giuseppe; Catanzariti, Rita; Tekin, U. Kagan; Sayit, Kaan

    2014-05-01

    In northern Turkey, the Intra-Pontide suture zone is represented by an east-west trending belt of deformed and/or metamorphic units located at the boundary between the Istanbul-Zonguldak terrane to the north and the Sakarya terrane to the south. These units can be regarded as issued from the Intra-Pontide domain, whose geodynamic history is still a matter of debate. Along the Akpinar-Araç-Bayramoren geotraverse, located in central Turkey, an ophiolite-bearing mélange known as the Arkot Dağ Mélange, is well-exposed along the Intra-Pontide suture zone. The Arkot Dağ Mélange plays a key role in the interpretation of the geodynamic history of the Intra-Pontide domain and can be described as a Late Santonian chaotic sedimentary deposit consisting of an up to 1000-m-thick succession of slide-blocks of different sizes and lithologies enclosed in a sedimentary matrix consisting of shales, coarse-grained arenites, pebbly mudstones and pebbly sandstones. The slide-blocks, from a few meters to hectometers in size, are represented by metamorphic rocks (mainly micaschists and gneisses), by ophiolites (peridotites, gabbros, IAT and BABB basalts and cherts) and by sedimentary rocks (cherts, neritic and pelagic limestone, marly limestone and ophiolite-bearing turbidites). The youngest age among the slide-blocks has been provided by the ophiolite-bearing turbidites where a late Coniacian nannofossil assemblage has been found. The cherts have provided a wide range of ages from the Middle Triassic to Late Cretaceous, whereas the fossils found in the limestone indicate Late Jurassic to Early Cretaceous ages. The matrix of the Arkot Dağ Mélange, even if unaffected by metamorphism, shows deformations represented by multiple meters-thick cataclastic shear zones at the boundaries of the mélange slices or inside of them. According to its features, the source area of the Arkot Dağ Mélange was most likely a continental and oceanic thrust sheet emplaced in the Late Cretaceous onto

  3. Flammer syndrome

    PubMed Central

    2014-01-01

    The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment. PMID:25075228

  4. Morbihan syndrome

    PubMed Central

    Veraldi, Stefano; Persico, Maria Chiara; Francia, Claudia

    2013-01-01

    We report a case of severe Morbihan syndrome (chronic erythematous edema of the upper portion of the face) in a 60-year-old man. The syndrome was characterized clinically by erythematous edema involving the forehead, glabella, and both eyelids, because of which the patient was not able to open completely his eyes. Furthermore, erythema and telangiectasiae were visible on the nose and cheeks. Laboratory and instrumental examinations were within normal ranges or negative. Histopathological examination showed dermal edema, perivascular and periadnexal lympho-histiocytic infiltrate, and sebaceous gland hyperplasia. Oral isotretinoin was ineffective despite the relatively long duration of the therapy (26 weeks). PMID:23741671

  5. [PFAPA syndrome].

    PubMed

    André, Suzete Costa Anjos; Vales, Fernando; Cardoso, Eduardo; Santos, Margarida

    2009-01-01

    PFAPA syndrome is characterized by periodic fever, pharyngitis, cervical adenitis and aphthous stomatitis. The bouts of fever can last for days or even weeks. Between crises, patients remain asymptomatic for variable periods. It appears before the age of five and has limited duration (4-8 years). Its aetiopathogeny is unknown. Corticoids are the treatment of choice. Tonsillectomy has been proposed as a solution but remains controversial. We present the case of a 4-year-old girl with PFAPA syndrome who underwent tonsillectomy in January, 2008, and we review the literature.

  6. [Wilkie's syndrome].

    PubMed

    Bognár, Gábor; Ledniczky, György; Palik, Eva; Zubek, László; Sugár, István; Ondrejka, Pál

    2008-10-01

    Loss of retroperitoneal fatty tissue as a result of a variety of debilitating conditions and noxa is believed to be the etiologic factor of superior mesenteric artery syndrome. A case of a 35 years old female patient with severe malnutrition and weight loss is presented, who developed superior mesenteric artery syndrome. Various theories of etiology, clinical course and treatment options of this uncommon disease are discussed. In our case, conservative management was inefficient, while surgical treatment aiming to bypass the obstruction by an anastomosis between the jejunum and the proximal duodenum (duodenojejunostomy) was successful. An interdisciplinary teamwork provides the most beneficial diagnostic and therapeutic result in this often underestimated disease.

  7. Reye's Syndrome

    PubMed Central

    Malcolmson, C.H.

    1987-01-01

    The author defines and discusses Reye's syndrome and the hypotheses relating to its causes and associating its incidence with that of chickenpox and influenza A and B. The recent decline in the incidence of Reye's syndrome appears to be related to the reduced use of Aspirin in children and adolescents. Although evidence so far is circumstantial, North American P(a)ediatric Associations have indicated that Aspirin should not be used to control fever in children who have viral infections but especially in children suspected of having chickenpox or influenza A or B. PMID:21264006

  8. Ultra-oxidized redox conditions in subduction mélanges? Decoupling between oxygen fugacity and oxygen availability in a metasomatic environment

    NASA Astrophysics Data System (ADS)

    Tumiati, Simone; Poli, Stefano; Godard, Gaston; Martin, Silvana; Malaspina, Nadia

    2014-05-01

    The manganese ore of Praborna (Italian Western Alps) is embedded within a metasedimentary sequence belonging to a subduction mélange equilibrated at high-pressure conditions (~2 GPa) during the Alpine orogenesis and record environmental conditions typical for a subducting slab setting. The pervasive veining of the ore and the growth of "pegmatoid" HP minerals suggest an open system with large fluid/rock ratio and a strong interaction with slab-derived fluids. This natural case provides an excellent natural laboratory for the study of the oxygen mobility in subducting oceanic slab mélanges at high-P, fluid-present conditions. The Mn-rich rocks in contact with the underlying sulphide- and magnetite-bearing metabasites, in textural and chemical equilibrium with the veins, contain braunite (Mn2+Mn3+6SiO12) + quartz + pyroxmangite (Mn2+SiO3), and minor hematite, omphacite, the epidote piemontite and spessartine-rich garnet. Similarly to Fe-bearing systems, Mn oxides and silicates can be regarded as natural redox-sensors, capable to monitor a process of fluid infiltration that could fix externally the intensive variable fO2 (or μO2). Sulphides are absent in these Mn-rich rocks, sulphates (barite, celestine) occurring instead together with As- and Sb oxides and silicates. On the basis of the observed assemblages, new thermodynamic calculations show that these mélange rocks are characterized by unrealistic ultra-oxidized states (ΔFMQ up to +12) if the chemical potential of oxygen (or the oxygen fugacity) is accounted for. However, if the molar quantity of oxygen in excess with reference to with reference to a system where all iron and manganese are considered to be ferrous, the ore appears only moderately oxidized, and comparable to typical subduction-slab mafic eclogites. Therefore, oxygen can be hardly considered a perfectly mobile component, even in the most favourable conditions. In the Earth's interior redox reactions take place mainly among solid oxides and

  9. Nephrotic Syndrome

    MedlinePlus

    ... child will have a relapse — where the nephrotic syndrome comes back after going away. In that case, treatment would begin again until the child outgrows the condition or it improves on its own./p> Reviewed by: Robert S. Mathias, MD Date reviewed: March 2014 previous 1 • ...

  10. Waardenburg's syndrome.

    PubMed

    Yesudian, D P; Jayaraman, M; Janaki, V R; Yesudian, P

    1995-01-01

    Three children in a family of five presented with heterochromia iridis, lateral displacement of inner canthi and varying degrees of sensorineural deafness. All the 3 showed iris atrophy. The father of the children had only heterochromia iridis. A diagnosis of Waardenburg's syndrome Type I was made in the children with the father probably representing a forme fruste of the condition.

  11. [Waardenburg's syndrome].

    PubMed

    Gimñenez, F; Carbonell, R; Pérez, F; Lozano, I

    1994-01-01

    Reporting one case of this condition type-2 with heterochromia iridis and cochlear deafness. The AA. review the syndrome's components and it nomenclature as well. They discuss about the convenience of including this deviation in the chapter of "diseases of the embryonic neural crest". The specific place of the gene responsibly in the chromosome-2 and the possibilities of genetic counselling are considered.

  12. Overtraining syndrome.

    PubMed Central

    Budgett, R

    1990-01-01

    This review discusses the overtraining syndrome which is characterized by fatigue and underperformance precipitated by stress of training. Other stresses, depression and an increased susceptibility to infections may be important. Treatment requires rest and a stress management program over 3 months. PMID:2097018

  13. Overtraining syndrome.

    PubMed

    Budgett, R

    1990-12-01

    This review discusses the overtraining syndrome which is characterized by fatigue and underperformance precipitated by stress of training. Other stresses, depression and an increased susceptibility to infections may be important. Treatment requires rest and a stress management program over 3 months.

  14. Aicardi syndrome

    MedlinePlus

    ... 20th ed. Philadelphia, PA: Elsevier; 2016:chap 591. US National Library of Medicine. Aicardi syndrome. Updated September 20, 2016. ghr.nlm. ... Support Get email updates Subscribe to RSS Follow us ... Developers U.S. National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894 U.S. Department ...

  15. Cushing's Syndrome

    MedlinePlus

    ... treatment of Cushing's syndrome. Current Drug Targets-Immune, Endocrine & Metabolic Disorders . 2004;4:335–342. Lin D, Loughlin K. Diagnosis and management of surgical adrenal diseases. Urology . 2005;66:476–483. Newell-Price J, ... & Nutrition Blood Diseases Diagnostic Tests La ...

  16. HELLP Syndrome.

    PubMed

    Sandvoß, Mareike; Potthast, Arne Björn; von Versen-Höynck, Frauke; Das, Anibh Martin

    2017-04-01

    The hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is frequently observed in mothers whose offspring have long-chain fatty acid oxidation defects. We previously found that fatty acid oxidation is compromised not only in these inborn errors of metabolism but also in human umbilical vein endothelial cells (HUVECs) from all pregnancies complicated by the HELLP syndrome. Sirtuins are oxidized nicotinamide adenine dinucleotide (NAD(+))dependent deacetylases linked to the metabolic status of the cell. SIRT 4 is known to have regulatory functions in fatty acid oxidation. The HELLP syndrome is often associated with short-term hypoxia. We studied sirtuins (SIRT 1, SIRT 3, and SIRT 4) in HUVECs from pregnancies complicated by the HELLP syndrome and uncomplicated pregnancies exposed to hypoxia (n = 7 controls, 7 HELLP; 0, 10, 60, or 120 minutes of 2% O2). Protein levels of SIRT 4 were significantly higher in HUVECs from HELLP compared to control after 60 and 120 minutes of hypoxia. The NAD(+) levels increased in a time-dependent manner.

  17. Rett Syndrome.

    ERIC Educational Resources Information Center

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  18. Rett Syndrome.

    ERIC Educational Resources Information Center

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  19. [SAPHO syndrome].

    PubMed

    Heldmann, F; Kiltz, U; Baraliakos, X; Braun, J

    2014-10-01

    The SAPHO syndrome, an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, is a rare disease which affects bones, joints and the skin. The main osteoarticular features are hyperostosis and osteitis. Osteoarticular symptoms predominantly occur on the anterior chest wall but the spine and the peripheral skeleton can also be involved. The most important skin affections are palmoplantar pustulosis and severe acne. The etiology of this syndrome remains unclear but infectious, immunological and genetic factors are involved. The diagnostic features of SAPHO syndrome are clinical and radiological. The most important diagnostic procedure is Tc-99 m bone scintigraphy but conventional x-rays as well as computed tomography (CT) and magnetic resonance imaging (MRI) can also contribute to the final diagnosis. Bone histology and positron emission tomography CT (PET-CT) may help to differentiate SAPHO syndrome from malignancies and infectious osteomyelitis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of treatment. The results obtained using antibiotics and disease-modifying antirheumatic drugs (DMARDs), such as sulfasalazine and methotrexate are inconsistent. Bisphosphonates and anti-tumor necrosis factor (anti-TNF) drugs have shown promising results in small studies but further research is still necessary.

  20. Waardenburg syndrome.

    PubMed Central

    Read, A P; Newton, V E

    1997-01-01

    Auditory-pigmentary syndromes are caused by physical absence of melanocytes from the skin, hair, eyes, or the stria vascularis of the cochlea. Dominantly inherited examples with patchy depigmentation are usually labelled Waardenburg syndrome (WS). Type I WS, characterised by dystopia canthorum, is caused by loss of function mutations in the PAX3 gene. Type III WS (Klein-Waardenburg syndrome, with abnormalities of the arms) is an extreme presentation of type I; some but not all patients are homozygotes. Type IV WS (Shah-Waardenburg syndrome with Hirschsprung disease) can be caused by mutations in the genes for endothelin-3 or one of its receptors, EDNRB. Type II WS is a heterogeneous group, about 15% of whom are heterozygous for mutations in the MITF (microphthalmia associated transcription factor) gene. All these forms show marked variability even within families, and at present it is not possible to predict the severity, even when a mutation is detected. Characterising the genes is helping to unravel important developmental pathways in the neural crest and its derivatives. Images PMID:9279758