Despite being well known that many forms of epilepsy are strongly influenced by genetics, scientists have long grappled with clearly defining this link. In a new study published in the journal Nature, however, researchers outline several key discoveries regarding the connection between the two most severe forms of epilepsy and the mutations associated with them.
"For generations we have been treating most forms of generalized epilepsies with no idea what causes the disease," said study co-author Dr. Ruben Kuzniecky, a professor of neurology at New York University's Langone Medical Center where he serves as co-director of the NYU Comprehensive Epilepsy Center and director of epilepsy research.
"Now, for the first time, we have identified clear genetic risk factors in patients with severe epilepsy."
Along with others, Kuzniecky sequenced DNA extracted from the blood samples of 149 children with infantile spasms and 115 with Lennox-Gastaut Syndrome, as well as analyzing the DNA of parents without the disease. In doing so, they uncovered de novo, or random, mutations on nine specific genes. Four of these mutations were completely new and had never before been associated with epilepsy.
"We found that each mutation carries substantial risk for these forms of epilepsy," Kuzniecky said, adding that it's "clear that rare individual mutations in different genes converge on specific biological pathways, suggesting a clear direction for personalized therapy and drug development."
These discoveries are the first to arise from a much larger undertaking known as the "Epilepsy Phenome/Genome Project" of which Kuzniecky is the chair. In all, the project includes a consortium of 27 medical centers from around the world and represents the largest investigation regarding the genetics of epilepsy to date.
"This project is one of the most ambitious undertakings in our field," Kuzniecky said. "It won't be long before it leads to genetic tools that will help us diagnose patients more accurately and tailor treatments specific to their form of epilepsy."
Currently, epilepsy affects between 1 and 2 percent of the world's total population, according to the researchers, and is believed to arise from a combination of inherited mutations as well as random mutations. By determining the cause and why some people with a family risk develop the disease and others do not, scientists hope to improve in both diagnosing and treating the condition.