Abstracts

Rationale: Angelman Syndrome (AS) is a neurodevelopmental genetic disorder consisting of multiple genetic subtypes characterized by global developmental delays, severe speech impairment, ataxia, and frequent laughter. Over 80% of affected individuals have epilepsy, often consisting of multiple seizure types and refractory to multiple medications. Although several studies have examined epilepsy in AS, all have been limited to a cohort of less than 100 people.Methods: An electronic survey was conducted through the Angelman Syndrome Foundation containing detailed questions relating to both the natural history of epilepsy in AS as well as various treatments of epilepsy in AS. Respondents were asked to describe their AS family member’s seizures as free text as well as choose answers from a list of choicesResults: There were 461 respondents of patients with AS, with an average patient age of 13.9 years (5.3 years at diagnosis), 56% of whom were male. Of the 461 patients, 396 (86%) had epilepsy, with 60% of those with epilepsy having multiple seizure types (average of 1.9 seizure types per respondent), and an average age of epilepsy onset of 3.8 years. Of those with epilepsy, 48% had generalized tonic-clonic seizures, 41% had atypical absence seizures, 40% had atonic seizures, 32% had apparent complex partial seizures, 12% had myoclonic seizures, 9% had tonic seizures, 6% had apparent partial or focal motor seizures, 2% had infantile spasms, and 1% had other seizure types or syndromes including Lennox-Gastaut Syndrome and gelastic seizures. A total of 59% of those with epilepsy had only generalized seizures, while only 11% had only apparent partial onset seizures (complex partial or focal motor), and 30% had mixed (both generalized and partial onset) seizures. While 31% of those with epilepsy were seizure free at the time of this survey, at least 28% of subjects over the age of 15 actually had a worsening of their epilepsy after puberty. Conclusions: Similar to previous studies, epilepsy was present in over 80% of individuals with AS, with a large percentage having multiple seizure types, most commonly generalized tonic-clonic seizures, atypical absence seizures, and atonic seizures. Epilepsy in AS is considered to be a generalized epilepsy, but 11% of those with seizures had only apparent partial onset seizures, while another 30% had both partial and generalized seizures. Those with deletions had a higher incidence of epilepsy as compared to those with UPD, imprinting defects, and UBE3A mutations, and likely also had more frequent seizures and more seizure types. Those with unknown mutations had epilepsy rates and seizure types similar to those with deletions. While epilepsy in AS is thought to improve with age, a significant percentage of those patients over age 15 actually had worsening of their epilepsy after puberty.