How I treat Angelman syndrome: an expert opinion

Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss of maternal UBE3A function, characterized by intellectual disability, absent speech, ataxic gait, and epilepsy in 80-90% of patients.

Seizure management remains symptomatic, guided by retrospective cohort data, caregiver surveys, and expert opinion in the absence of randomized controlled trials. This review systematically addresses the complete neurology-centered clinical management pathway for AS - from diagnostic recognition, neurodevelopmental and seizure characterization, delineation of characteristic EEG changes, differentiation from genetic mimickers, and identification of nonepileptic events that commonly mimic seizures, through pharmacotherapy selection, status epilepticus recognition and treatment, trigger prevention, and transition of care, to lifelong multisystem follow-up - while situating these principles within the rapidly shifting landscape of disease-modifying therapies now entering Phase 2 and 3 evaluation.

Levetiracetam and clobazam are currently the favored first-line agents; valproate and clonazepam are efficacious but carry a more complex adverse-effect profile. Emerging reports describe cannabidiol oil use. The ketogenic and low hypoglycemic index diets offer adjunctive options for refractory cases. Three antisense oligonucleotide programs and the first gene replacement therapy have entered Phase 2/3 trials, marking a fundamental shift toward disease modification. Multidisciplinary, multisystem, lifelong care is essential, with careful attention to caregiver burden.