Treatment responses to antiseizure medication in children with Angelman syndrome.

BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder with epilepsy affecting up to 90% of the children. Although several studies have examined antiseizure medications (ASMs) in children with AS, preferred ASMs vary between countries and while new ASMs have become available in clinical practice in recent years, their impact on epilepsy treatment in children with AS remains unclear. We report on the frequency of most prescribed ASMs, responder rates and rate of severe side effects of ASM in a natural history cohort. Epilepsy and epilepsy-related parameters were analyzed including differences between genetic subgroups. METHODS: A total of 101 children with AS who visited the Angelman center Munich between 2019 and first quarter of 2025 were included in this retrospective analysis. Epilepsy characteristics, frequency of prescribed ASMs, responder rate and severe side effect rate were recorded. RESULTS: Epilepsy was present in 75%, with a higher incidence in the deletion genotype. Most patients experienced seizures rather rarely, but one in five had daily or weekly seizures. Seizure frequency was higher in early childhood. Therapy-refractory epilepsy was observed in 34% of AS children with epilepsy. Rate of therapy-refractory epilepsy and seizure burden was higher in the deletion group. Among the most prescribed ASMs (ethosuximide, levetiracetam and valproate), ethosuximide and valproate demonstrated the highest responder rate (>50% reduction of seizures) in 78% and 75% of patients, respectively, closely followed by levetiracetam (64%). The reported side effect rate of ASM did not differ between the most prescribed medications. CONCLUSIONS: The three most prescribed ASMs (valproate, ethosuximide and levetiracetam) in our cohort showed high responder rates in children with Angelman Syndrome. Overall seizure burden and rates of therapy-refractory epilepsy were lower than previously reported, suggesting that combining new and established ASMs may improve seizure outcomes in this population.