Scientists Uncover Genes Responsible for Severe Childhood Epilepsies

Scientists may have taken a step forward when it comes to better understand severe, difficult-to-treat forms of childhood epilepsy. They've discovered the gene mutations responsible, which disrupt functioning in the synapse, the highly dynamic junction at which nerve cells communicate with one another.

Epilepsies are some of the most common disorders of the central nervous system. They affect up to 3 million patients in the U.S. and up to one third of these epilepsies are resistant to treatment with medication. Severe epilepsies, though, are particularly devastating in children, which makes understanding the underlying causes that much more important.

The current study actually adds to a list of gene mutations associated with these severe epilepsy syndromes, called epileptic encephalopathies. The scientists discovered these mutations in the first place by sequencing the exomes of 356 patients with severe childhood epilepsies, as well as their parents. They looked for "de novo" mutations-ones that appeared in affected children, but not in their parents. In all, they found 429 de novo mutations.

Actually identifying mutations wasn't enough, though. The scientists then analyzed the children. In 12 percent of the children, the mutations were considered to unequivocally cause the child's epilepsy.

"Everybody has one or two de novo mutations and it is our task to find those changes that can cause disease," said Ingo Helbig, co-author of the new study, in a news release. "We pulled out those genes that have more mutations in patients with epilepsy than you would expect by chance. These genes will hopefully tell us a bit more about the underlying disease mechanisms and how we can address them with new treatments."

What was particularly interesting was the finding that there is a gene called DNM1, which was mutated in five patients. This particular gene carries the code for dynamin-1, a structural protein that plays a role in shuttling small vesicles between the body of the neuron and the synapse. These vesicles are structures that contain neurotransmitters. On a network level, many of the genes that were mutated in patients had a clear connection with the function of the synapse.

The new findings could help researchers better understand these severe epilepsies, which could improve treatments in the future. By finding new genes, the scientists can discover what underlying causes affect epilepsies and begin to develop new therapies.

The findings are published in the American Journal of Human Genetics.