New Evidence for Genetic Basis of Epilepsy

Study shows risk may not be as high as people think

Published on February 26, 2014by Elaine Meyer

Close relatives of people with epilepsy are at a greater risk than the general population of developing the neurological disorder, according to a new study led by Dr. Ruth Ottman, professor of epidemiology (in Neurology and the Gertrude H. Sergievsky Center) with co-author Dr. W. Allen Hauser, professor emeritus of epidemiology, and other colleagues from Columbia’s Department of Neurology, the Mayo Clinic, and the University of Calgary.

Although this group is not the first to find that risk for epilepsy runs in families, past studies had potentially serious methodological limitations according to the paper, which will run in the March issue of the journal Brain and is available online.

For this study, the researchers analyzed data from the Rochester Epidemiology Project, a partnership of three medical centers in Minnesota, including the Mayo Clinic, which allows all records of medical care received by patients residing in the area it covers to be used for population studies.

The researchers studied the families of all 660 residents of Rochester, Minnesota, who were born in 1920 or later, with new cases of epilepsy occurring during a 60 year period, from 1935-1994.  Among the nearly 2,500 parents, siblings, and children of these individuals, the risk of developing epilepsy by age 40 was 4.7 percent—three times that of the general population.

Those at highest risk were relatives of individuals with idiopathic generalized epilepsy, which is believed to have a strong genetic basis, though abnormalities in the nervous system are not apparent on imaging studies. Also at greater risk were relatives of individuals who have types of epilepsy associated with intellectual or motor disability that is likely related to prenatal or developmental problems. Epilepsies of unknown cause and prenatal/developmental cause clustered within families, suggesting shared genetic influences.

The family members of individuals whose epilepsy had a known cause occurring after birth, such as a stroke, severe traumatic brain injury, or brain tumor were not at increased risk.

Epilepsy is characterized by recurrent seizures caused by abnormal electrical discharges in the brain. Approximately 1.3 percent of individuals will develop epilepsy by age 40, and 3 percent will develop it before age 80, according to Dr. Ottman. While epilepsy cannot be cured, seizures can be controlled with medication in about two-thirds of affected individuals, according to the U.S. Centers for Disease Control and Prevention.

It is believed that genes are involved in the majority of cases, although how exactly the disorder comes about is complicated, and usually involves interplay among the environment and multiple genes. Dr. Ottman and her research team are known for having discovered a gene, LGI1, that causes a certain type of epilepsy that runs in families, known as autosomal dominant partial epilepsy with auditory features.

“One of the most important concerns of people with epilepsy is whether the disorder is inherited—what are the risks in their family members, and especially in their offspring?” says Dr. Ottman.

Although genetic research is moving quickly, in most affected individuals the specific genes that affect risk of the disorder have not been identified.

“That means we need to rely on solid risk estimates from rigorous studies like this one to obtain answers about risks to family members,” Dr. Ottman says. “One thing that’s important about our findings is that people with epilepsy tend to overestimate the risk in their children, and we found that risks in offspring are only about 4 percent overall, and are less than 10 percent even in the highest risk groups—so that even though risk is higher than in the general population, more than 90 percent of the offspring will remain unaffected.”

The study comes during a time of intense debate about the overestimation of risk through screenings, which was reignited recently after a large Canadian study found that one in five women is falsely diagnosed with breast cancer through a mammogram.

Over-diagnosis of disease can lead to individuals getting treated with unneeded and sometimes harmful drugs or procedures.

Edited by Barbara Aaron and Dana March