Benign Childhood Epilepsy with Centrotemporal Spikes and the Focal Sharp Wave Trait is not Linked to the Fragile X Region

Abstract

Benign childhood epilepsy with centrotemporal spikes (BCECS, benign rolandic epilepsy) is a common form of genetically determined localisation-related epilepsy of childhood. The characteristic age-dependent focal sharp wave (fsw) found on the EEG in this disorder segregates as a dominant trait in families with probands with BCECS. Seizures occur in a significant proportion of individuals with the fragile X syndrome in association with EEG abnormalities comparable to those found in BCECS. The possibility of a common genetic basis for these disorders was investigated by linkage analysis. Six pedigrees with probands with BCECS were analysed using a marker locus DXS548, close to the fragile X site, fra (X). Obligate recombinants between DXS548 and the fsw trait were observed in all six families. Assuming X-linked dominant inheritance and penetrance values of 0.4 (male) and 0.1 (female) a negative lod score of -6.823 was obtained at zero recombination and lod scores of -2.0 at 10cM either side of the fra (X) locus. These results exclude an important candidate gene for this common childhood disorder.

Key words

Epilepsy - Focal sharp wave trait - Fragile X - Linkage analysis