Genetic epidemiology of epilepsy.

Epilepsy is one of the most common neurologic disorders, affecting approximately 4 percent of individuals at some time in their lives (1). An inherited contribution to its etiology has been suspected for centuries, yet until recently, little progress has been made in understanding the genetic influences on susceptibility. This slow progress is owed in part to methodological problems in previous studies and in part to underlying complexity in the genetic contributions. In most forms of epilepsy, the familial distribution is inconsistent with a simple Mendelian model, and the mode of inheritance is uncertain. Both genetic and environmental factors may contribute to susceptibility, and it is unclear how they interact in their influence on risk. Epilepsy is clinically very heterogeneous, and the important genetic and environmental effects may differ across clinically defined subsets or syndromes. Even within narrowly defined clinical syndromes, different susceptibility genotypes or environmental factors may influence risk in different families. On the other hand, a single susceptibility locus could influence risk for different syndromes in different individuals, either through allelic heterogeneity, pleiotropic expression of a single allele, or the modifying effects of environmental factors. Epilepsy is defined by recurrent (^2) unprovoked seizures (2). Seizures are considered to be unprovoked when they occur in the absence of an immediate precipitating factor (although an injury to the central nervous system may have occurred at some time in the past). Epilepsy is distinguished from the two other major classes of seizure disorders: acute symptomatic seizures, in which seizures occur only in association with acute structural or metabolic insults to the central