Clinical and genetic analyses of 11 children with epilepsy associated with SCN2A gene variations / 中华神经医学杂志

ABSTRACT

Objective:To summarize the clinical and genetic characteristics of children with epilepsy associated with SCN2A gene variations. Methods:A retrospective study was performed. Eleven children with epilepsy admitted to Department of Pediatric Neurology, Linyi People's Hospital from January 2017 to December 2022 were included; all of them had pathogenic SCN2A gene mutation. Genetic results and clinical data as epileptic seizure type/frequency, intelligence and motor development of these 11 children were collected. Epilepsy-related variations and pathogenesis of SCN2A gene were analyzed, and their correlations with clinical phenotypes in these children were analyzed. Results:Among the 11 patients, 6 had self-limited epilepsy (4 with variation in the intracellular domain and 2 in the transmembrane domain), 1 had febrile convulsion accompanied by childhood absent epilepsy (with variation in the intracellular domain), and 4 had developmental epileptic encephalopathy (2 with variation in the extracellular domain and 2 with variation in the transmembrane domain). SCN2A gene was missense mutation in these 11 children, and the mutation site in 6 children was not reported before. Various forms of video EEG discharge were noted, and 1 child with self-limited epilepsy showed transient multifocal epileptic discharge during frequent seizures. Oxcarbazepine and topiramate were effective for self-limiting epilepsy, and lamotrigine was effective in 1 child with late-onset epileptic encephalopathy. Eleven patients were followed up for (66±32) months; the age ranged from 8 months to 11 years and 6 months at the last follow-up; 10 patients had seizure remission and 1 had uncontrolled seizure. Conclusions:Besides self-limited epilepsy and developmental epileptic encephalopathy, SCN2A gene mutations are also associated with febrile convulsion and childhood absent epilepsy. Phenotypic differences are highly correlated with mutation locations; developmental epileptic encephalopathy associated variants are mostly located in extracellular domains, while self-limited epileptic variants are mostly located in intracellular domains.