Battaglia A. The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev. 27, 365-369

Stella Maris Clinical Research Institute for Child and Adolescent Neurology and Psychiatry, via dei Giaicnti 2, Calambrone, Pisa 56018, Italy.
Brain and Development (Impact Factor: 1.88). 09/2005; 27(5):365-9. DOI: 10.1016/j.braindev.2004.08.006
Source: PubMed


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.

30 Reads
  • Source
    • "A history of mild to moderate developmental delay was observed in 13 of our int dup(15) subjects. Hypotonia is found in almost all individuals with idic 15q duplications [Battaglia, 2005], while we observed hypotonia in more than half (60%) of our study population. In our study, only subject 801-018 had seizures (6%), which was most likely due to a periventricular leukomalacia that was not found in any other subjects and would not produce, on its own, the increased beta activity we described in other subjects (Table 2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 08/2013; 6(4). DOI:10.1002/aur.1284 · 4.33 Impact Factor
  • Source
    • "Low birth weight might contribute to development delays. Clinical presentations observed in the patient with tetrasomy 15q11q13 overlap those described in Western patients with similar 15q aneusomy [2]. Although both tetrasomy and pentasomy patients shared similar clinical profiles, pentasomy patient appeared to be more severely affected than tetrasomy patient with regard to development delays and speech problems. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The proximal chromosome 15q is prone to unequal crossover, leading to rearrangements. Although 15q11q13 duplications are common in patients with developmental delays and mental impairment, 15q aneusomies resulting in greater or equal to 4 copies of 15q11q13 are rare and no pentasomy 15q11q13 has been reported in the literature. Thus far, all reported high copy number 15q11q13 cases are from the West populations and no such study in Chinese patients have been documented. Dosage-response pattern of high copy number 15q11q13 on clinical presentations is still a subject for further study. Case Presentation In this study, we characterized two Han Chinese patients with high copy number 15q11q13. Using chromosome banding, high resolution SNP-based cytogenomic array, Fluorescence in situ hybridization, and PCR-based microsatellite analysis, we identified two patients with tetrasomy 15q11q13 and pentasomy 15q11q13. Both 15q11q13 aneusomies resulted from a maternally inherited supernumerary marker chromosome 15, and each was composed of two different sized 15q11q13 segments covering the Prader-Willi/Angelman critical region: one being about 10 Mb with breakpoints at BP1 and BP5 regions on 15q11 and 15q13, respectively, and another about 8 Mb in size with breakpoints at BP1 and BP4 regions on 15q. Both patients presented with similar clinical features that included neurodevelopmental delays, mental impairment, speech and autistic behavior, and mild dysmorphism. The patient with pentasomy 15q11q13 was more severely affected than the patient with tetrasomy 15q11q13. Low birth weight was noted in patient with pentasomy 15q1q13. Conclusions To the best of our knowledge, this is the first case of pentasomy 15q11q13 and the first study of high copy number 15q11q13 in Han Chinese patients. Our findings demonstrate that patients with tetrasomy and pentasomy of chromosome 15q11q13 share similar spectrum of phenotypes reported in other high copy number 15q11q13 patients in the West, and positive correlation between 15q11q13 copy number and degree of severity of clinical phenotypes. Low birth weight observed in the pentasomy 15q11q13 patient was not reported in other patients with high copy number 15q11q13. Additional studies would be necessary to further characterize high copy number 15q11q13 aneusomies.
    BMC Medical Genetics 01/2013; 14(1):9. DOI:10.1186/1471-2350-14-9 · 2.08 Impact Factor
  • Source
    • "A questionnaire concerning psychomotor and speech development was developed and a Child Behavior Check List (CBCL) was applied [Achenbach, 1991, 1992; Verhulst, 1996] to collect global information on behavioral characteristics. All clinical findings of groups A and B together were compared with those reported on previously published (limited) series with large SMC(15)s [Robinson et al., 1993; Mignon et al., 1996; Hou and Wang, 1998; Wandstrat et al., 1998; Webb et al., 1998; Borgatti et al., 2001; Chifari et al., 2002; Battaglia, 2005, 2008; Crolla et al., 2005; Dennis et al., 2006; Valente et al., 2006]. In addition, the separate findings of groups A and B SMC(15)s were compared with the "
Show more