Genetic testing in the diagnosis and management of idiopathic epilepsy: Current practice, future prospects and challenges

Abstract

Epilepsy is a common chronic neurological disorder with a complex pathogenesis. Genetic factors play a pivotal role in epilepsy, particularly in idiopathic and earlyonset forms. Advances in next-generation sequencing technologies, including gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS), have substantially transformed molecular diagnostic strategies for epilepsy. The diagnostic yield of genetic testing ranges from 20 to 50%, depending on the testing approach and clinical subgroup, with the highest yield observed in patients with early-onset or drug-resistant epilepsy. Epilepsy-associated genes predominantly encode ion channels and proteins involved in synaptic transmission, neurodevelopment, and metabolism. Identification of pathogenic variants strengthens the diagnosis, facilitates personalised treatment selection, and optimises patient management. However, the interpretation of genetic variants and the limited availability of reference data remain major clinical challenges. Therefore, standardising analytical workflows and establishing population-specific genetic databases are essential for improving the diagnostic performance of genetic testing. This review summarises current trends in genetic testing for idiopathic epilepsy, evaluates the diagnostic performance of molecular testing, and discusses its potential applications in precision medicine.