Authors: Fakir Zineb , Tazzite Amal , Berrada Sarah , Dehbi Hind

Abstract

Background: The 15q11.2–q13 duplication syndrome (OMIM: 608636) is a rare autosomal dominant neurodevelopmental disorder caused by genomic rearrangements within a highly unstable chromosomal region prone to low-copy repeat–mediated duplications. This region contains imprinted genes involved in Angelman and Prader–Willi syndromes, making the parental origin relevant to its pathogenicity. Clinically, affected individuals present with autism spectrum disorder, intellectual disability, developmental and speech delays, seizures, and hypotonia. To date, no case has been reported in Morocco.

Case Presentation: We report an eight-year-old girl referred to our genetics department for global developmental delay, absence of speech, intellectual disability, autism spectrum disorder, and facial dysmorphia. Neurological examination revealed motor delay, including tiptoe walking and incontinence, while EEG, thyroid function, and auditory evoked potentials were normal. Whole exome sequencing revealed a heterozygous 9.0 Mb duplication at 15q11.2–q13.3 encompassing imprinted genes such as UBE3A, SNRPN, and GABRB3, consistent with 15q11–q13 duplication syndrome (OMIM: 608636).

Conclusion: Most cases of 15q11.2-q13 duplication syndrome are maternally inherited. Maternally expressed imprinted genes, particularly UBE3A, play a central role in the pathogenesis of autism spectrum disorder and other developmental abnormalities associated with this condition. The genotype-phenotype correlation in this syndrome is highly complex, due to incomplete penetrance. We present the first reported instance of 15q11.2-q13 duplication syndrome in Morocco. Our findings contribute to the growing body of evidence implicating genes within the 15q11-q13 region in autism spectrum disorder.

Keywords: 15q11.2-q13 duplication syndrome , neurodevelopmental disorder, autism spectrum disorder, case report, Morocco.