Hexasomy of the 15q11q13 region: a detailed report and review of the literature

Abstract

Hexasomy of the Prader-Willi/Angelman Syndrome Critical Region (PWASCR; chromosome 15q11-q13) is very rare with only 13 patients being described to date. The region is known for its high susceptibility to genomic rearrangements, and extra copies within the region have been shown to be associated with distinct but variable clinical features of intellectual disability, epilepsy, global developmental delay amongst others. We present a 10-year-old girl with moderate to severe intellectual disability, cerebral palsy, seizures, autistic features and challenging behaviours. Her karyotype is 47,XX,+mar[25]/46,XX[5]. On chromosome analysis using G-banding, we identified a very large dicentric supernumerary marker chromosome 15q11-q13. Microarray analysis and metaphase fluorescence in-situ hybridisation using the SNRPN gene specific to 15q11.2-q13.3 region showed 87 % of cells containing 6 signals and 13 % of cells containing 2 signals. This represents mosaicism for a partial hexasomy of the long arm of chromosome 15q. We also reviewed and consolidated the literature of all reported patients with hexasomy of PWASCR, and found that amongst all 14 patients (including ours), despite some variation in phenotype, all patients had seizures, and the majority had intellectual disability and challenging behaviours.