The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder.
ABSTRACT The chromosome region 15q11q13 is known for its instability, and many rearrangements may occur in this imprinted segment: deletions associated either with Angelman syndrome (AS) or with Prader-Willi syndrome (PWS), according to parental origin; translocations; inversions; and supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) constitute the most common of the heterogeneous group of the extra structurally abnormal chromosomes, and their presence results in tetrasomy 15p and partial tetrasomy 15q. Inv dup(15), containing the Prader-Willi/Angelman syndrome region, are associated with altered behaviour, developmental delay/mental retardation, and seizures/epilepsy. Clinicians should suspect this syndrome in any infant/child with early central hypotonia, minor dysmorphic features, developmental delay, autism or autistic-like behaviour, and who subsequently develops hard to control seizures/epilepsy. Diagnosis is confirmed by standard cytogenetic techniques and FISH analysis. Although, about 100 cases have been reported to date, limited data are available on the natural history. To obtain better information on diagnosis and outcome in a clinical setting, we reviewed the available literature on clinical and behavioural phenotype of inv dup(15) syndrome.
- SourceAvailable from: Conny van Ravenswaaij-Arts
Dataset: Kleefstra sSMC 15 AJMG 2010
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ABSTRACT: Prader-Willi syndrome (PWS), a neurodevelopmental disorder primarily characterized by hyperphagia and food preoccupations, is caused by the absence of expression of the paternally active genes in the proximal arm of chromosome 15. Although maladaptive behavior and the cognitive profile in PWS have been well characterized, social functioning has only more recently been systematically examined. Findings to date indicate the social impairment exhibited may reflect specific difficulty interpreting and using social information effectively. In addition, evidence suggests that there is an increased risk of social deficits in people with the maternally-derived uniparental disomy (mUPD) subtype of PWS in comparison to those with 15q11-13 paternal deletion (DEL). Using the Social Responsiveness Scale (SRS) and the Social Competence Inventory, our goal was to compare social functioning in PWS to individuals with autism spectrum disorder (ASD). Participants with mUPD scored similarly to the ASD group across most SRS domains. All groups had difficulty with social competence, although the DEL group scored highest on prosocial behavior. Findings suggest further characterization of social behavior in PWS is necessary to aid in advancing the understanding of the contributions of genes in the 15q11-13 critical region to ASD susceptibility, particularly with respect to the overexpression of maternally expressed genes in this region, as well as aiding in awareness and development/implementation of interventions.Journal of Autism and Developmental Disorders 05/2012; DOI:10.1007/s10803-012-1547-3
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ABSTRACT: Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu- and heterochromatic 15q material. On the basis of size, the clinically relevant SMC(15)s can be subdivided into type A, “large” asymmetric and type B, “small” symmetric SMC(15)s. Type B SMC(15)s contain the triplicated 15pter to BP3 (located at 26.5 Mb) region, while type A SMC(15)s consist of 15pter → BP4(28.5 Mb)::BP5(30.5 Mb) → 15pter. In this study, the clinical and molecular features of 18 patients with A and B SMC(15)s and two patients with a partial trisomy 15q were reviewed. Questionnaires (including Child Behavior Check Lists) were used to assess behavior and developmental features in more detail. The marker size and parental origin were determined by multiplex ligation-dependent probe amplification (MLPA). Based on the MLPA results, the majority of patients (14/18) had type A SMC(15)s. The phenotype observed did not show significant differences between types A and B SMC(15)s. A high prevalence of autistic-like behavior, attention problems, aggressive behavior, anxiety, and sleeping problems was reported. Motor and speech development varied extensively among the patients. An association was found between positive seizure history and degree of intellectual disability. © 2010 Wiley-Liss, Inc.American Journal of Medical Genetics Part A 09/2010; 152A(9):2221 - 2229. DOI:10.1002/ajmg.a.33529