小児てんかんにおける標的遺伝子パネル検査：診断結果と遺伝的知見の拡大

Epilepsy is a genetically heterogeneous disorder with a high burden in the pediatric population. Advances in next-generation sequencing (NGS) have enhanced molecular diagnosis, enabling more accurate subclassification and targeted interventions.

This study aimed to evaluate the diagnostic utility of epilepsy gene panel testing in a large pediatric cohort and to characterize the clinical and genetic features of molecularly diagnosed cases.

A retrospective analysis was conducted on 516 pediatric epilepsy patients who underwent targeted gene panel testing between 2021 and 2025 at a tertiary medical center. Only pathogenic and likely pathogenic variants were considered diagnostic.

A molecular diagnosis was established in 81 patients (15.7 %). The most frequently implicated genes were KCNQ2, SCN1A, CACNA1A, SLC2A1, and SCN2A, collectively accounting for 43.2 % of all diagnoses. Despite this concentration, pathogenic variants were distributed across 37 different genes, emphasizing the high genetic heterogeneity. Most diagnosed patients had seizure onset in infancy, particularly within the first year of life. Notably, two-thirds of neonates with seizures had pathogenic KCNQ2 variants. Additionally, 23 of the diagnostic variants (29.9 %) were novel, underscoring the evolving spectrum of epilepsy-associated mutations.

Epilepsy gene panel testing is a valuable diagnostic tool in pediatric clinical practice. The identification of pathogenic variants across a wide range of genes - including a high proportion of novel mutations - supports the integration of genetic testing into the routine evaluation of pediatric epilepsy for improved etiological clarification and long-term management.