Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?

TLDR

Angelman syndrome is a neurological disorder marked by severe intellectual disability, absent speech, seizures, gait disturbances, and characteristic facial features, most commonly caused by maternal chromosome 15 deletions, with rare cases arising from paternal uniparental disomy. The study aims to determine whether paternal uniparental disomy of chromosome 15 is associated with a milder Angelman phenotype. In a Swiss cohort of 14 sporadic Angelman patients, two unrelated females with paternal chromosome 15 isodisomy exhibited a milder phenotype, lacking typical facial features, having only late‑onset mild seizures, and maintaining largely intact gross motor function, and both were born to older fathers. © 1994 Wiley‑Liss, Inc.

Abstract

Abstract The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age‐dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11–q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late‐onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients. © 1994 Wiley‐Liss, Inc.