U. research links gene to epilepsy

University of Utah medical researchers have identified a gene with mutations that causes febrile seizures and contributes to a severe form of epilepsy known as Dravet syndrome in some of the most vulnerable patients — infants 6 months and younger.

For infants and children who suffer febrile seizures or have Dravet syndrome, the study offers hope where there often is little to be found, according to Kris Hansen, president of the Epilepsy Association of Utah and mother to a child with Dravet syndrome.

"Dravet is such a hard syndrome to control, and any research that gives us reasons for what is happening with our children and hope for the future is absolutely amazing," Hansen said. "This medical breakthrough will bring prospects of relief to families dealing with the ongoing challenges of Dravet syndrome and febrile seizures."

Epilepsy is a disorder of many types of seizures that affects nearly 3 million people in the United States, with approximately 200,000 new cases reported each year.

Patients with Dravet syndrome can have febrile and other seizures severe enough to stunt mental and social development.

This breakthrough could identify whether they have a mutation in the SCN9A gene, which the researchers found causes seizures by affecting sodium channels in the brain.

Infants who have the mutation might well be better off not receiving sodium channel blockers, some of the most common anticonvulsant drugs, because they could make a sodium channel-induced seizure worse, the researchers report in the Sept. 11 edition of PLoS Genetics.

First author Nanda A. Singh, Ph.D., a researcher in the University's Eccles Institute of Human Genetics, said the SCN9A mutation is the fifth gene discovered to cause febrile seizures and, before now, was not suspected in seizures or epilepsy.

"This new gene gives us a much needed novel target for developing more effective drugs to treat those children with debilitating seizures," Singh said.

Groundwork for the study was laid by two U. of U. School of Medicine physicians, Joel Thompson, M.D., and Francis M. Filloux, M.D., professor of pediatrics and neurology.

The two doctors met a patient in the 1990s whose family had a history of febrile seizures. After studying the DNA of 46 members of the extended family, researchers at the U. identified an area on chromosome 2 as a likely place to find the gene mutation associated with the family's seizures. Using that data, they pinpointed the SCN9A mutation as the seizure-causing gene in the family.

Febrile seizures are the most common form of early childhood seizures and strike up to one in 20 children in North America. Most infants outgrow them, but in some cases the seizures continue into adulthood.

This study was a collaboration of researchers from the University of Utah School of Medicine's Department of Human Genetics, divisions of Pediatric Neurology and Medical Genetics, and the College of Pharmacy's Anticonvulsant Drug Development Program.

Researchers from the University of Washington and University of Antwerp, Belgium, collaborated on the study.

Mark F. Leppert, Ph.D., professor of human genetics in the University of Utah School of Medicine, was the study's senior author.