The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals

Cornelia de Lange Syndrome (CdLS) is a multisystem congenital anomaly disorder. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), encoding components of the sister chromatid cohesion apparatus, are responsible for ∼ 50-60% of CdLS cases. Recent studies have revealed a high degree of genomic rearrangements (e.g. deletions and duplications) in the human genome, which result in gene copy number variations (CNV). CNVs have been associated with a wide range of both Mendelian and complex traits including disease phenotypes such as Charcot-Marie-Tooth type 1A, Pelizaeus-Merzbacher, Parkinson, Alzheimer, autism and schizophrenia. Increased versus decreased copy number of the same gene can potentially cause either similar or different clinical features. We identified duplications on chromosomes 5 or X using genome wide array Comparative Genomic Hybridization (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. Junction sequences analyses revealed the involvement of three genomic rearrangement mechanisms. The patients share some common features including mental retardation, developmental delay, sleep abnormalities, and crainofacial and limb defects. The systems affected are the same as in CdLS, but clinical manifestations are distinct from CdLS; particularly the absence of the CdLS facial gestalt. Our results confirm the notion that duplication CNV of genes can be a common mechanism for human genetic diseases. Defining the clinical consequences for a specific gene dosage alteration represents a new “reverse genomics” trend in medical genetics that is reciprocal to the traditional approach of delineation of the common clinical phenotype preceding the discovery of the genetic etiology.

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“…F, female; M, male; NA, information not available*Common features for Cornelia de Lange syndrome (CdLS) 20 21 23 54…”

Section: Resultsmentioning

confidence: 99%

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange

Yan

Zhang

Brundage

et al. 2008

Journal of Medical Genetics

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“…A small number of previous studies have evaluated sleep in adults and children with CdLS and there are conflicting findings regarding the incidence of sleep disturbance as well as its relation to behavioral problems. Approximately 12-72% of individuals with CdLS experience problems with sleep including settling and waking at night although most studies are limited in their characterization of the disturbances [3,4]. There has not yet been a study evaluating sleep disordered breathing or obstructive sleep apnea in this population.…”

Section: Introductionmentioning

confidence: 94%

Characterization of sleep disturbance in Cornelia de Lange Syndrome

Stavinoha

Kline

Levy³

et al. 2011

International Journal of Pediatric Otorhinolaryngology

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“…However, the association between CdLS and ASD has recently received more attention. Prevalence rates of autism in CdLS range from 50 -67% Basile, Villa, Selicorni & Molteni, 2007;Berney, et al, 1999;Bhyuian et al, 2006, Moss et al, 2008. Using the Childhood Autism Rating Scale (CARS; , Oliver et al (2008) reported that 32.1% of 54 individuals with CdLS scored within the 'severe autism' category of the CARS compared to only 7.1% of a matched control group of individuals with intellectual disability, suggesting that the relationship between CdLS and ASD is not solely accounted for by associated degree of disability.…”

Section: Autism Spectrum Disorder In Cornelia De Lange Syndromementioning

confidence: 99%

The Assessment and Presentation of Autism Spectrum Disorder and Associated Characteristics in Individuals with Severe Intellectual Disability and Genetic Syndromes

Moss

Howlin

Oliver

2012

The Oxford Handbook of Intellectual Disability and Development

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This chapter considers the prevalence and nature of Autism Spectrum Disorders (ASD) and associated symptomatology in the intellectual disability population, with particular focus on three genetically determined syndromes—Fragile X syndrome, Tuberous Sclerosis Complex, and Rett syndrome—that have received particular attention with respect to their association with ASD. It then considers the importance of accurate assessment and diagnosis of ASD in individuals with genetically determined syndromes. It describes the methods and tools available for assessing ASD in individuals with intellectual disability, and explores the appropriateness of these assessments for identifying ASD in individuals with genetically determined syndromes associated with intellectual disability.

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The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals

Cited by 90 publications

References 30 publications

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange

Characterization of sleep disturbance in Cornelia de Lange Syndrome

The Assessment and Presentation of Autism Spectrum Disorder and Associated Characteristics in Individuals with Severe Intellectual Disability and Genetic Syndromes

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