How I treat Angelman syndrome: an expert opinion

Area of Science:

• Neuroscience
• Genetics
• Clinical Neurology

Background:

• Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by loss of maternal UBE3A gene function.
• Key features include intellectual disability, absent speech, motor difficulties, and frequent epilepsy (80-90% of patients).

Purpose of the Study:

• To provide a comprehensive review of the neurology-centered clinical management pathway for Angelman syndrome.
• To discuss current symptomatic treatments and emerging disease-modifying therapies.

Main Methods:

• Systematic review of diagnostic recognition, seizure characterization, and EEG findings in AS.
• Analysis of pharmacotherapy selection, status epilepticus management, and trigger prevention.
• Evaluation of current and emerging disease-modifying treatments.

Main Results:

• Current seizure management is symptomatic, with levetiracetam and clobazam as first-line options; ketogenic diets can be adjunctive.
• Several disease-modifying therapies, including antisense oligonucleotides and gene replacement, are in Phase 2/3 trials.
• Lifelong, multidisciplinary care is essential for managing multisystem involvement and caregiver burden.

Conclusions:

• Neurologic management of AS requires early diagnosis, symptomatic seizure control, and consideration of emerging disease-modifying agents.
• A shift towards disease modification is anticipated with ongoing clinical trials.
• Comprehensive, lifelong care is critical for patients with Angelman syndrome.