Diagnostic Genetic Findings From Exome Sequencing in a Cohort of 1,109 Children With Epilepsy

Genetic testing has emerged as a transformative tool for the diagnosis and treatment of epilepsy. The aim of this study was to characterize the genetic basis of pediatric epilepsy.

We analyzed a cohort of 1,109 children with epilepsy who underwent whole-exome sequencing. Genetic findings were interpreted based on medical records and genetic testing results.

Genetic diagnostic results were found in 405 of 1,109 patients, with a diagnostic yield of 36.5%. The SCN1A (40/1,109, 3.6%) was the most frequently affected gene, followed by the PRRT2 (26/1,109, 2.3%) and SCN2A (10/1,109, 0.9%). In total, 138 genes were identified with 337 total detections. Gene ontology analysis revealed enrichment in ion channel-related genes (30.0%, 101/337), catalytic activity-related genes (19.6%, 66/337), and pathway-related genes (14.5%, 49/337). Multivariate logistic regression showed that younger age at onset (OR = 0.87, 95% CI 0.81-0.94, p < 0.001), developmental delay or intellectual disability (OR = 2.25, 95% CI 1.62-3.12, p < 0.001), and facial dysmorphisms (OR = 2.30, 95% CI 1.06-5.00, p = 0.036) were associated with a higher likelihood of achieving a genetic diagnosis. Negative results were obtained in 51.4% (570/1,109) of patients.

This single-center study provides a comprehensive overview of the genetic landscape of pediatric epilepsy, enhancing our understanding of the genetic basis and offering insights for clinical diagnosis and genetic counseling. These findings underscore the clinical utility of genetic testing in pediatric epilepsy.