Abstract
We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning disability, in which 60%-90% have NSD1 pathogenic variants. Patients were recruited from clinics and referral from support groups. Those with seizures and a clinical diagnosis of Sotos syndrome were included. Phenotyping data were collected via structured clinical interview and chart review. Forty-nine patients were included. Twenty had NSD1 testing results available; of these, 15 (75%) had NSD1 pathogenic variants. Seizure onset age ranged from 3 months to 12 years. Staring spells (absence or focal impaired awareness seizure) were the most frequently reported semiology (33/49; 67%), followed by febrile seizures (25/49; 51%) and afebrile bilateral tonic-clonic seizures (25/49; 51%). Most patients (33/49; 67%) had multiple seizure types. The majority (33/49; 67%) had seizures controlled on a single antiseizure medication or no medication. Nine (18%) had drug-resistant epilepsy. Epilepsy syndromes included febrile seizures plus, Lennox-Gastaut syndrome, childhood absence epilepsy, and generalized tonic-clonic seizures alone. The seizure phenotype in Sotos syndrome most commonly involves staring spells, afebrile tonic-clonic seizures or febrile convulsions; however, other seizure types may occur. Seizures are typically well-controlled with medication, but drug-resistant epilepsy occurs in a minority.