Centrotemporal spikes in families with rolandic epilepsy

Abstract

OBJECTIVE: To localize a gene predisposing to benign epilepsy of childhood with centrotemporal spikes (BECTS). BACKGROUND: BECTS, or rolandic epilepsy, is the most prevalent idiopathic epilepsy syndrome in childhood. Functional relevant defects in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AChR) have been demonstrated in autosomal dominant nocturnal frontal lobe epilepsy, which, like BECTS, is an idiopathic partial epilepsy. METHODS: A DNA linkage study was conducted screening all chromosomal regions known to harbor neuronal nicotinic AChR subunit genes. Twenty-two nuclear families with BECTS were analyzed. RESULTS: In an "affected-only" study, best p values and lod scores were reached between D15S165 and D15S1010 on chromosome 15q14. In multipoint nonparametric linkage analysis a nominal p value of 0.000494 was calculated by GENEHUNTER. Best parametric results were obtained under an autosomal recessive model with heterogeneity (multipoint lod score 3.56 with 70% of families linked to the locus). These markers are localized in direct vicinity to the alpha 7 subunit gene of the AChR. CONCLUSIONS: We found evidence for linkage of BECTS to a region on chromosome 15q14. Either the alpha 7 AChR subunit gene or a closely linked gene are implicated in pedigrees with BECTS. The disorder is genetically heterogeneous. Surprisingly, the same chromosomal area has been reported to be linked to the phenotype in families with an auditory neurophysiologic deficit as well as in families with juvenile myoclonic epilepsy, another idiopathic but generalized epilepsy syndrome.