Genetic Diagnosis of Dravet Syndrome Using Next Generation Sequencing-Based Epilepsy Gene Panel Testing

Dravet syndrome, one of the epileptic encephalopathies of childhood, is a genetic epilepsy caused by SCN1A mutation in 70-80% of the cases. Other genetic variants have been revealed in SCN1A-negative patients with Dravet syndrome. We investigated the utility of targeted gene panel testing in patients with Dravet syndrome and delineated the genotype-phenotype correlation. Targeted epilepsy gene panel testing including 40 genes was performed in 24 patients clinically diagnosed with Dravet syndrome. Detected variants were classified according to the guidelines of American College of Medical Genetics and Genomics 2015 and validated by Sanger sequencing. We investigated the relationship between clinical characteristics and genetic mutations. Causative variants including 16 SCN1A and two PCDH19 mutations were detected in 18 patients (75.0%). There were 27 variants with uncertain significance related to diverse genes other than SCN1A Analysis of clinical phenotypes of the detected variants did not reveal significant differences in patients with those variants. Dravet syndrome can be caused by various disease-causing variants whose clinical manifestations may differ according to the causative genes. Therefore, targeted epilepsy gene panel testing is efficient for genetic diagnosis of Dravet syndrome and may help in establishing therapeutic plans and forecasting disease course and prognosis.