Tracking Down the Roots of Childhood–Onset Epilepsy

People with epilepsy have disrupted patterns of neuronal activity that can cause strange sensations, emotions and behavior. Sometimes, these disruptions in neuronal activity can lead to convulsions, muscle spasms and loss of consciousness. In adults, epilepsy most often is caused by traumatic brain injury, infection, tumors or other neurological conditions. On the other hand, epilepsy in children more often directly is related to genetics.

Michael Hammer, PhD, research scientist with the Arizona Research Labs, director of the University of Arizona Genetics Core, and director of the Technology and Innovation Division of the Center for Applied Genetics and Genomic Medicine, built his career studying human population genetics. For years, his laboratory analyzed the ways evolution affects the patterns of genetic variation that we see throughout the human genome.

More recently, however, the direction of Dr. Hammer’s research group made a dramatic turn after his daughter was diagnosed with a rare form of epilepsy when she was 6 months old. Her diagnosis eventually led Dr. Hammer down a different path, examining how a handful of genetic mutations can cause epilepsy and related disorders in children.

In 2012, Dr. Hammer’s laboratory found the mutation that caused his daughter’s epilepsy: a single change in the DNA sequence in a gene called SCN8A. This was the first reported case of epilepsy caused by a mutation in the SCN8A gene.

The SCN8A gene codes for one part of a large protein complex known as the sodium channel. These channels control how sodium atoms in the human body flow in and out of cells. Sodium channels are in all cells of the body, including cells of the brain. In neurons, sodium channels regulate how cells communicate with each other, and specifically control the generation and transmission of electrical signals in the nervous system.

Changes in the sequence of the SCN8A gene can change the function of the sodium channel. People with SCN8A-related epilepsy have mutations that increase the flow of sodium ions into nerve cells, leading to an over-excited state in the brain and uncontrolled electrical signals. This hyperactive state of neurons leads to abnormal brain function and epilepsy.

After initially discovering the SCN8A mutation in his daughter, Dr. Hammer started reaching out to other families of children with epilepsy to identify the underlying genetic causes of childhood-onset epilepsy on a more global scale. “This information can be really helpful for families,” he says. “Family members finally get answers about the cause of their child’s illness. Even more relevant, knowing what is causing the disease can help clinicians to better identify which treatments can help improve symptoms and which ones should be avoided. This is extremely valuable information because some standard treatments for epilepsy do not work optimally in people with SCN8A mutations.”

Dr. Hammer joined with other families who learned that their child had a variant in SCN8A to initiate a support group, and he also manages a community website for people facing similar struggles. This website also hosts a registry, which gathers data from people with SCN8A mutations from around the world (http://scn8a.net). Today, his website and registry have collected data from more than 200 families of children with SCN8A-related epilepsy, yielding important information for families, clinicians and researchers.

Dr. Hammer’s work now focuses on finding treatments to improve the symptoms and quality of life for people with epilepsy.

“Everyone is somewhat susceptible to seizures, but different people have different thresholds to overcome. Some people have a high threshold that makes it more difficult for them to get to the point of having a seizure. Others have a lower threshold where seizures happen more easily,” says Dr. Hammer. “People with epilepsy have an extremely low threshold, and therefore, they have seizures more frequently.”

Dr. Hammer is currently working to find treatments that increase the seizure threshold of patients with childhood-onset epilepsy. The research team hopes that increasing the seizure threshold in patients with epilepsy can help decrease the frequency of seizures, giving these patients a better prognosis and a better quality of life.

For more information about events supporting epilepsy, please go to http://www.purpleday.org/events. To learn more about SCN8A-related epilepsy, please visit http://scn8a.net.