Benign childhood epilepsy with centrotemporal spikes and electroencephalography trait are not linked to EBN1 and EBN2 of benign neonatal familial convulsions

Abstract

Purpose: The electroencephalographic hallmark of benign childhood epilepsy with centrotemporal spikes (BECTS, or rolandic epilepsy) are characteristically shaped centrotemporal spikes and sharp waves (CTS). This EEG trait, but not BECTS itself, has been reported to follow an autosomal dominant mode of inheritance with incomplete penetrance and age dependence. CTS therefore represents a neurobiologic marker for the increased risk of developing BECTS. Benign neonatal familial convulsions (BNFC) like BECTS is an idiopathic age-dependent epilepsy with a benign course. Observations of benign neonatal seizures and BECTS in the same individual are well documented. Neonatal seizures with benign course were found in increased numbers in a series of CTS carriers. Two genetic loci, EBN1 and EBN2, have been mapped in families with BNFC, making these two loci strong candidates for the CTS trait underlying BECTS. The aim of this study was to determine whether these two epilepsy syndromes are allelic disorders. Methods: Linkage analysis was performed in 12 families with probands with BECTS and one or more relatives with CTS in the EEG with or without BECTS by using polymorphic DNA markers. Results: Assuming an autosomal mode of inheritance with penetrances of 0.9 and 0.45, respectively, both loci were consistently excluded. Conclusions: The CTS trait and EBN1 and EBN2 segregate independently. BECTS and BNFC therefore appear to be genetically distinct entities. Benign neonatal seizures may be a underrecognized symptom of the CTS trait itself.