Preponderance of female sex in the transmission of seizure liability in idiopathic generalized epilepsy

Background: the predominance of the female sex in the transmission of seizure liability is a known phenomenon. However, all hitherto published genetic studies are based on reported seizure frequencies only. The aim of this investigation was to reexamine this problem by combining clinical and family EEG data. Methods: families of 82 index cases fulfilling the following core criteria were ascertained; (1) definite clinical and EEG diagnosis of idiopathic generalized epilepsy with absences and/or myoclonic astatic seizures; (2) obtainable history and EEG recordings from both the parents and one or more siblings. EEG recordings were evaluated for different genetic traits of epileptiform EEG activity (EPA), as well as genetic characteristics of background activity. Results: of the 164 parents 9% suffered from seizures. EPA was detected in 24% of probands' mothers versus 12% in fathers. Altogether 28% of probands' mothers were positive for seizures or EPA versus 16% of the fathers. Of parents with EPA in the EEG only about 50% showed seizures. Twenty one percent of all the parents and 60% of the mothers with EPA showed generalized alpha-activity (9% in controls). In contrast, in mothers without EPA a 'non alpha-EEG' was overrepresented. In probands' siblings, 14% showed seizures and 23% showed seizures or EPA. In probands' siblings with EPA seizure risk was 50 versus only 8% in siblings without EPA. The highest siblings risk was conferred by SW and an affected mother. If a father was affected, risk for the siblings of probands was almost equal to that in families with both the parents unaffected. Siblings of female probands were more often affected than those of male probands (19 vs. 8%; P < 0.05). Generalized SW occurred in 17% of probands' siblings, in girls siblings significantly more often than in boys siblings (25 vs. 9%; P < 0.01). Conclusion: clinical history and family EEG equally contribute information contents. Female preponderance in transmission of seizure liability is the result of a complex of genetic interactions that include the generalized alpha-EEG. (C) 2001 Elsevier Science B.V. All rights reserved.