P&S Journal: Fall 1995, Vol.15, No.3
Clincal Advances: By Lynne Christensen
Genetics and Epilepsy
Researchers have found a genetic link for the most common form of epilepsy, partial epilepsy, long thought to result most often from head injury, vascular disease, or errors in brain development.
Dr. Ruth Ottman, associate professor in the Gertrude H. Sergievsky Center and the Columbia School of Public Health, and colleagues identified the first clue that genetics could play a role in partial epilepsy. In a May issue of Nature Genetics, Dr. Ottman described localization of a gene for partial epilepsy to chromosome 10 by studying families of 2,000 adults with epilepsy.
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, characterized by seizures that emanate from a specific brain region and sometimes begin on one side of the body. Generalized epilepsy, thought to involve the entire brain from the start of the seizure, is considered genetic in most cases. Several genes have been mapped for generalized epilepsy.
"While this finding will not immediately impact on prevention or treatment options for people with epilepsy, it is an important conceptual development," says Dr. Timothy Pedley, coauthor of the Nature Genetics paper and director of the Comprehensive Epilepsy Center at CPMC. "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. Now we know that may not be true in all cases."
In an NIH-funded ongoing study of genetic contributions to epilepsy, Dr. Ottman's team collected information on seizure disorders in the families of nearly 2,000 adults with epilepsy. The team identified a family in which individuals in three successive generations are affected with partial epilepsy in a pattern strongly suggestive of a genetic link.
"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," says Dr. 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."
Most members of the family who carry the gene developed the disease, but some family members have not. 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.
Now that the general location of a gene that raises risk for partial epilepsy has been identified, the search for a gene and its product can begin.
"This finding suggests that there may be more universal genetic factors relating to epilepsy than previously thought," says Dr. W. Allen Hauser, professor of neurology and of public health at the Sergievsky Center 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." Dr. Hauser also coauthored the research paper.
Both classifications of epilepsy are treated with drugs, although partial epilepsies do not 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.