Genetic Epilepsy

As an increasingly high percentage of epilepsies are identified as genetic, epileptologists are moving from pure excitement about precision diagnosis to targeted management and therapies. Although we are not yet in an era of gene therapy for all, there are aspects of epilepsy care which should be tailored to the increasingly specific information a genetic diagnosis offers. This issue of Practical Neurology examines the evaluation, management, and treatment of epilepsies with a genetic etiology.

Ms. Ivanisevic begins this issue with an update on genetic testing technologies and their applicability to early-onset epilepsy. Ms. Ivanisevic describes testing yield, turnaround time, cost, and the psychological weight of incomplete or uncertain information for a family as crucial factors influencing which genetic test to order.

Next, Drs. Fonkeu and Ellis remind us that genetic testing is not limited to the pediatric setting. Increasingly specific diagnoses in the adult population may offer additional treatment recommendations and prognostic information for adults with new or well-established yet undiagnosed epileptic syndromes.

Whereas identifying epilepsy as genetic in etiology was a relative contraindication to epilepsy surgery in the past, Drs. Mann, Gaillard, and Armour describe how genetic testing is an essential component of a surgical work-up to be done previously or concurrently with other components like high-resolution MRI and functional imaging. They highlight the fact that germline and somatic variants underlie a subset of benign tissue overgrowth and focal cortical dysplasias which can serve as epileptogenic foci.

It is crucial to emphasize the benefit of dietary therapies, which can be just as effective if not more effective than commonly used antiseizure medications in achieving seizure remission. Dr. Bonno focuses on therapeutic benefits of the ketogenic diet for certain genetic syndromes, such as glucose transporter type 1 deficiency syndrome (GLUT1-DS). Drs. Johnson, Armstrong, and Fong describe the diagnosis and pathophysiology of GLUT1-DS and reinforce the role of dietary therapy as a precision medicine approach to GLUT1-DS.

Finally, Drs. Squires, Garrity and Broomall provide practical guidance for genetic epilepsy patient management in the pediatric intensive care unit. When a ‘one-liner’ carries a gene name, we may need to pause before proceeding with standard medication additions or restricting oral intake for an extended period. Standardizing care for more common diagnoses also may reduce errors or the need for a prolonged hospital stay.

The rise of precision medicine and the rapid expansion of genetic testing have produced exciting new innovations in the management and treatment of epilepsy and offer hope to physicians, patients, and caregivers impacted by genetic epilepsies.