Epilepsies in twins: genetics of the major epilepsy syndromes

We studied twins to examine the genetics of epilepsy syndromes. We ascertained 358 twin pairs in whom one or both reported seizures. After evaluation, 253 of 358 (71%) had seizure disorders and 105 pairs were false positives. Among the monozygous (MZ) pairs, more were concordant for seizures (48 of 108; casewise concordance = 0.62 +/- 0.05) than among the dizygous (DZ) pairs (14 of 145; casewise concordance = 0.18 +/- 0.04). In 94% of concordant MZ pairs, and 71% of concordant DZ pairs, both twins had the same major epilepsy syndrome. When analyzed according to major epilepsy syndrome, the casewise concordances for generalized epilepsies (MZ = 0.82; DZ = 0.26), both idiopathic (MZ = 0.76; DZ = 0.33) and symptomatic (MZ = 0.83; DZ = 0), were greater than those for partial epilepsies (MZ = 0.36; DZ = 0.05), with intermediate values seen for febrile seizures (MZ = 0.58; DZ = 0.14) and unclassified epilepsies (MZ = 0.53; DZ = 0.18). We conclude that genetic factors are particularly important in the generalized epilepsies but also play a role in the partial epilepsies. The high frequency of concordant MZ pairs with the same major syndrome strongly suggests there are syndrome-specific genetic determinants rather than a broad genetic predisposition to seizures.