Objectives: We aimed to investigate the genetic etiology of epilepsy in children, and to analyze the nature of genetic variation, the function of related genes, and the genotype-phenotype relationship. Moreover, the impact of the genetic diagnosis on prognosis and prenatal diagnosis will be discussed.
Methods: We recruited 218 pediatric epilepsy patients with onset ages ranging from postnatal 5 days to 3 years during a three-year collection period. WES was conducted only for the probands to screen for possible candidate genes.
Results: A total of 55 patients (25.2%) had positive genetic diagnoses. Autosomal dominant gene variants were the most common (34/55; 61.8%) and de novo variants (31/34; 91.2%) consistent with an autosomal dominant mode of inheritance. Among 64 variants identified in 35 genes, 33 (51.6%) were novel, previously unreported. Ion channel genes play critical roles in the pathogenesis of epilepsy, accounting for 58.8% (20/34) of the variants. A total of 31 (56.4%) families chose to have a prenatal diagnosis in subsequent pregnancies based on the genetic diagnosis.
Conclusion: Our data suggest that applying WES in patients with epilepsy of unknown etiology can improve counseling and management. Early establishment of genetic diagnosis was necessary for counseling on recurrence risk and prenatal diagnosis. A large number of unreported variants were detected, widening the known spectrum of genetic variation related to epilepsy risk.
Keywords: De novo; Genetic analysis; Novel variants; Pediatric epilepsy; Whole-exome sequencing.
© 2022. Fondazione Società Italiana di Neurologia.