Clinical and Genetic Insights into Angelman Syndrome: A Retrospective Study of 26 Cases in Morocco

Abstract

Angelman syndrome (OMIM #105830) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A gene within the imprinted 15q11.2–q13 region. Although its clinical and molecular characteristics have been well described in European and Asian populations, data from low- and middle-income countries remain scarce. This retrospective study aimed to characterize the clinical and molecular features of Angelman syndrome in a Moroccan cohort and investigate genotype–phenotype correlations. Twenty-six patients with molecularly confirmed Angelman syndrome diagnosed between 2018 and 2022 at the Department of Medical Genetics, Hassan II University Hospital, Fez, were included. Molecular diagnosis was established using methylation-specific PCR, fluorescence in situ hybridization, and UBE3A sequencing. The cohort showed a female predominance (61.5%) and a median age at diagnosis of 5.7 years, indicating delayed diagnosis. Core clinical features included intellectual disability (100%), absent speech (96%), seizures (87%), Angelman syndrome-specific EEG abnormalities (87%), ataxia (87%), and hypersalivation (92%). Molecular analyses identified 15q11.2–q13 deletions in 77% of patients, imprinting defects or uniparental disomy in 11.5%, and UBE3A variants in 11.5%. Patients with maternal deletions exhibited a more severe neurological phenotype. This study, the largest Moroccan cohort of Angelman syndrome, highlights delayed diagnosis and limited access to molecular testing. Although hypersalivation was frequently observed, this finding should be interpreted cautiously, as it may reflect severe oromotor dysfunction and impaired swallowing rather than increased salivary secretion. These findings support earlier recognition, comprehensive molecular diagnosis, and improved access to genetic services in resource-limited settings.

Clinical trial number: Not applicable.