Genetic Testing in Pediatric Epilepsy

This article summarizes the emerging landscape of pediatric epilepsy, highlighting genetic contributions, and reviews approaches to genetic evaluation for pediatric epilepsy in this context.

Advances in understanding the genetic basis for epilepsy over the last several years have been due in large part to the identification of de novo genetic variation underlying sporadic severe epilepsy in children; the genetic underpinnings of the more common epilepsies remain largely unknown. Next-generation sequencing approaches have been added to the repertoire of clinical tests for the evaluation of pediatric epilepsy, improving our ability to make positive diagnoses. Yields of over 50% are now being reported in selected groups of patients. Genetic variation contributing to the risk for pediatric epilepsy spans continua of scale and influence. The highest yield of genetic testing is currently in children with sporadic severe epilepsy caused by de novo variation. The approach to genetic evaluation and interpretation of results requires an understanding of (1) the epilepsy phenotype and (2) the particular advantages and limitations of the different genetic tests available. Our understanding of genetic variation will continue to improve over time and "negative" results are best conceptualized as "unresolved" or "negative for now."