Targeting the Future: Genetics and Epilepsy

Prior to genetic testing in the lab, epidemiologic studies and analysis of individual families shared the earliest evidence for genetic contributions to chronic conditions. In 1951, neurologist William G. Lennox studied more than 4,000 epilepsy cases, focusing on individuals living with epilepsy who did not have any evidence of structural brain damage.

Is Epilepsy Inherited?

He examined the incidence of epilepsy in family members and differences in the concordance rates of epilepsy in identical versus fraternal twins. His seminal report concluded that although having a relative with epilepsy increases one’s own risk of having epilepsy, it is not a straightforward relationship. He pioneered the idea that genetic influences on epilepsy were often multi-factorial and not always a direct one-to-one relationship.

“[People with epilepsy] are carriers of not one, but a great many, qualities,” said William G. Lennox in 1951. “[All of] these transmitted traits determine, or help to determine, not only physical structure and physiological function of the body, but also the even more important characteristics of intelligences, personality and social consciousness.”

In the rare epilepsy syndromes, most often affecting children and representing the more severe forms of epilepsy, the genetic culprit can be clearer than in the general epilepsy population.

Dr. Lennox and his team during a review session. Photo credit: Boston Children's Hospital

Genetic Testing Advances

Advances in genetic testing over the past two decades have led to a rapid increase in our understanding of the spectrum of epilepsies. The development of genomic technologies including chromosomal microarrays (which examine microscopic deletions or duplications of DNA) and next generation gene panels, whole exome, and whole genome sequencing (which can do rapid sequencing of large amounts of DNA) have helped to grow understanding of the genetic underpinnings of epilepsies and allowed for acceleration of genetic discovery.

Next generation sequencing has aided the identification of gene variants causing epilepsies, allowing for a higher diagnostic yield in people tested. Over the past two decades, we have identified hundreds of different genes linked with causing epilepsy.

Role of Genetic Registries

Harnessing the knowledge that erupts from advances in science is key to shared progress. Genetic registries play an important role in enhancing the power of genetic discovery to benefit people impacted by epilepsy.

A registry gathers and keeps information about people with a certain condition to support and encourage research into that condition. To expedite research into the rare epilepsies, over 30 rare epilepsy organizations have joined forces with the Epilepsy Foundation, Research Triangle Institute, and Columbia University to create the first ever Rare Epilepsy Network (REN).

Rare Epilepsy Network

With seed funding from the Patient-Centered Outcomes Research Institute (PCORI), the REN patient registry collects information about people living with rare epilepsies to better understand these conditions, improve treatments, and improve the lives and quality of care of people living with them. Over 1,450 individuals have contributed to the registry, sharing their or their loved ones’ medical history and experiences on a wide range of issues. We are actively working on ways that these natural history reports could be linked with genetic testing results.

In 2019, the PCORI funding ended and the Epilepsy Foundation committed to housing the registry in-house. We do not want this important data to be lost. Along with our REN partners, we created a public dashboard for the community to begin to learn from the information collected.

Please visit here to learn more. These insights and dashboards will continue to grow over time. The REN is a production of the over 30 partners working together, and we are extremely proud to be facilitating the network to spur new insights into this area. We cannot do this alone.