Partial epilepsy, in which seizures begin in a specific brain region, has long been thought to result most often from head injury, vascular disease, or errors in brain development--not genetics.
The finding is the first clue that genetics could play a role in partial epilepsy and ultimately may lead to improved diagnosis and a better understanding of the development of the disease.
Principal investigator Ruth Ottman, associate professor in the Gertrude H. Sergievsky Center and Columbia's School of Public Health, and colleagues describe localization of a gene for partial epilepsy to chromosome 10 in the May 1 issue of Nature Genetics.
At some time in their lives, about 10 million Americans suffer from epilepsy, a common neurological disorder that causes symptoms ranging from recurrent convulsive seizures involving all or part of the body to momentary spells of impaired consciousness. Sixty percent of them have partial or localization-related epilepsy, which is characterized by seizures that emanate from a specific brain region and sometimes begin on one side of the body.
While this finding will not immediately impact on prevention or treatment options for people with epilepsy, it is an important conceptual development, said Timothy Pedley, a coauthor and director of the Comprehensive Epilepsy Center at Columbia-Presbyterian Medical Center.
Until now most people have assumed that, with the exception of some childhood epilepsies, partial epilepsies as a rule were not genetic. In other words, partial epilepsy was considered an acquired disorder. That may not be true in all cases.
In an ongoing study of genetic contributions to epilepsy, Ottman's team collected information on seizure disorders in the families of nearly 2,000 adults with epilepsy.
The gene that may be responsible for epilepsy in this family was localized to chromosome 10. By identifying the area on chromosome 10 where a gene or genes responsible for partial epilepsy may exist, Ottman's team has succeeded in demonstrating a genetic cause in at least some cases of partial epilepsy.
"Because our analysis was restricted to a single family, we cannot estimate the proportion of familial epilepsy that can be attributed to this susceptibility gene," said Ottman.
However, even if the mutation found in this family is rare, the identification of its product and its effect may have important implications for determining what is causing the epilepsy.
Eleven individuals in the family developed the disorder between ages 8 and 19. They have similar seizure types and six report hearing a ringing or humming sound that steadily grows louder before seizures. Partial epileptic seizures often are preceded by a warning such as a sound or the twitching of an arm or a leg on one side of the body. The seizure that follows may be confined to one part of the body or spread to include the whole body.
While most members of the family who carry the gene developed the disease, some family members with the gene have not developed the disease. This suggests other factors may be required in order for the gene to cause epilepsy. Environmental factors or another gene may be required before the gene causes the disorder.
"We don't know why some people escape being affected," said Ottman, "but this would be an exciting area to study to get clues on how we might prevent the disorder in the future."
Once the gene product is identified, researchers can study how it does its damage and causes epilepsy.
"This finding suggests that there may be more universal genetic factors relating to epilepsy than previously thought," said W. Allen Hauser, professor of neurology and public health at the Gertrude H. Sergievsky Center at Columbia's College of Physicians & Surgeons and a world-renowned expert on the epidemiology of epilepsy. "Ultimately, we may now be able to identify the specific mechanisms that lead to epilepsy and may be able to intervene in whatever the process is." Hauser is also a coauthor on the paper.
Both classifications of epilepsy are treated with drugs, although partial epilepsies don't respond as well to medication and may be more difficult to control.
Seventy-five percent of those with generalized epilepsy will eventually outgrow the disease and stop having seizures and 65 percent of partial epilepsy patients will recover.
This research was funded by the National Institutes of Health.
The Comprehensive Epilepsy Center at Columbia-Presbyterian Medical Center provides multidisciplinary diagnostic and treatment services to patients with epilepsy and is a major referral site for patients with uncontrollable seizures.
The Gertrude H. Sergievsky Center at Columbia-Presbyterian Medical Center focuses on epidemiologic approaches to the study of neurodevelopmental disorders.