Zaburzenia neurorozwojowe związane z genem UNC13A u dzieci: postacie epilepsji i odpowiedź na leki przeciwpadaczkowe

PURPOSE: Pathogenic UNC13A variants are increasingly recognized in pediatric neurodevelopmental disorders, but epilepsy phenotypes and antiseizure medication (ASM) responses remain poorly characterized. This study aimed to define the epileptic spectrum of UNC13A-related disorders in children and identify effective ASM strategies. METHODS: We retrospectively analyzed 10 children with pathogenic/likely pathogenic UNC13A variants. Clinical data, seizure phenotypes, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and ASM outcomes were systematically evaluated. RESULTS: We identified 10 patients, including eight with de novo heterozygous variants and two with biallelic variants. Most missense variants were localized within the critical hinge regions of Munc13-1, with p.Pro814Leu identified as a recurrent variant in three individuals. Six patients (60%) presented with developmental and epileptic encephalopathy, with a median seizure onset of 19 months (range: 5 months-7 years). Focal seizures were the predominant seizure type, and all affected patients experienced status epilepticus. Febrile seizures occurred in half of these patients. While seizures were largely refractory, levetiracetam (LEV) was observed effective in three out of four treated patients. Genotype-phenotype analysis revealed distinct clinical trajectories: biallelic variants resulted in catastrophic early-onset symptoms and early mortality, whereas heterozygous variants were characterized by drug-resistant epilepsy, tremor and ataxia. CONCLUSIONS: UNC13A variants represent an underrecognized cause of developmental and epileptic encephalopathy in children, characterized by refractory seizures, a high incidence of status epilepticus, and increased susceptibility to febrile seizures. Preliminary observations noted favorable clinical outcomes in a small subset of patients treated with LEV.