Multigene Panel Testing in Pediatric Epilepsy: Diagnostic Yield and Clinical Implications

Purpose: Genetic testing is increasingly being incorporated into the evaluation of pediatric epilepsy. This study aimed to describe the clinical characteristics of patients with epilepsy who received positive genetic diagnoses through gene panel testing and additional genetic analyses; identify clinical factors associated with a genetic diagnosis; and evaluate the clinical implications of genetic diagnoses.Methods: We retrospectively reviewed pediatric patients with epilepsy evaluated at a tertiary referral center between January 2020 and December 2024 who underwent testing with a multigene panel curated to include 29 early-onset epilepsy genes. Selected patients with negative results underwent chromosomal microarray analysis and trio-based whole-exome sequencing. Clinical variables, including age at seizure onset, developmental status, neuroimaging findings, and family history, were analyzed. The impact of a positive genetic diagnosis was evaluated with respect to changes in antiseizure medication and family counseling.Results: A total of 79 patients were included. Pathogenic or likely pathogenic variants were identified in 26.6% (21/79) of patients through gene panel testing. Among panel-negative cases, five additional patients received a genetic diagnosis, yielding an overall diagnostic rate of 32.9% (26/79). Among the clinical variables analyzed, earlier seizure onset (age <12 months) was the only factor significantly associated with gene panel positivity (P=0.002). Genetic diagnoses led to clinically meaningful management changes in 46.2% (12/26) of patients.Conclusion: In this real-world pediatric epilepsy cohort, multigene panel testing provided substantial diagnostic yield and influenced clinical management. Seizure onset before 12 months was the strongest predictor of gene panel positivity, supporting routine genetic evaluation in early-onset epilepsy.