Evidence for distinct genetic influences on generalized and localization-related epilepsy

Determining the existence of syndrome-specific genetic factors in epilepsy is essential for phenotype definition in genetic linkage studies, and informs research on basic mechanisms. Analysis of concordance of epilepsy syndromes in families has been used to assess shared versus distinct genetic influences on generalized epilepsy (GE) and localization-related epilepsy (LRE). However, it is unclear how the results should be interpreted in relation to specific genetic hypotheses.

To assess evidence for distinct genetic influences on GE and LRE, we examined concordance of GE and LRE in 63 families containing multiple individuals with idiopathic or cryptogenic epilepsy, drawn from the Epilepsy Family Study of Columbia University. To control for the number of concordant families expected by chance, we used a permutation test to compare the observed number with the number expected from the distribution of individuals with GE and LRE in the study families.

Of the families, 62% were concordant for epilepsy type, and 38% were discordant. In all analyses, the proportion of concordant families was significantly greater than expected.

This suggests that some genetic influences predispose specifically to either GE or LRE. Because of the ascertainment bias resulting from the selection of families containing multiple individuals with epilepsy, we could not test whether there are also shared genetic influences on these two epilepsy subtypes. Population-based studies will be needed to explore these results further.