Clinical, Molecular, and Neurophysiological Features in Angelman Syndrome

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder associated with a unique type of epilepsy. AS is caused by loss of function of the ubiquitin protein ligase E3A (UBE3A) gene. Most cases of AS (70%) are caused by an approximate 5 Mb deletion in chromosome 15q11-q13 of the maternally derived allele; other causes include paternal uniparental disomy of chromosome 15 (5%), imprinting defects (5%), and UBE3A mutations (10%), with the genetic cause yet to be determined in the remaining 10% of cases. Many seizure types are present in AS, with myoclonic, absence, and tonic-clonic seizures being common. Characteristic findings of electroencephalography in AS include persistent rhythmic theta activity, anterior dominant rhythmic high-amplitude delta (2-3 Hz) activity or spikes and slow waves, and posterior dominant spikes and sharp waves mixed with 3 to 4 Hz high-amplitude slow waves. UBE3A has been shown to regulate both the glutamatergic and gamma-aminobutyric acidergic systems; further dissection of the molecular mechanisms of UBE3A action in mouse models and individuals with AS would facilitate a greater understanding of the pathophysiology of epilepsy.