AUTOSOMAL DOMINANT TRANSMISSION OF CENTROTEMPORAL SPIKES IN ROLANDIC EPILEPSY FAMILIES

Objectives: Rolandic epilepsy (RE) has a complex genetic inheritance. Centrotemporal spikes (CTS) are the hallmark EEG diagnostic feature of RE. Studies in the 1960s and 1970s suggested CTS in Rolandic epilepsy families were transmitted in autosomal dominant fashion, but this assumption has been challenged because of possible diagnostic and methodological errors. We therefore assessed the mode of transmission of CTS in RE families using stringent diagnostic criteria for RE, and single ascertainment.

Methods: We ascertained 38 patients with typical RE focal sensorimotor symptoms, CTS on EEG, and normal neuroimaging. Ascertainment was independent of the affectedness of other family members. Siblings of RE patients aged 5 to 15 years underwent one hour long sleep-deprived EEG recordings. EEGs were analyzed by a neurophysiologist blind to the study hypothesis and the identity and disease status of the subjects. Segregation ratio estimate was corrected for ascertainment by the Weinberg method.

Results: 25 siblings of RE patients underwent sleep EEG recordings. 11 of 25 (44%, sd 9.9%) siblings showed CTS on their recordings (six male). Two of the 11 also had a diagnosis of RE. Five of 11 CTS+ siblings had a history of phonological speech and/or developmental reading disorder, while six were asymptomatic. The proportion of CTS+ siblings is more consistent with an autosomal dominant rather than autosomal recessive mode of transmission. X-linkage is excluded.

Conclusion: CTS are a necessary component of RE and our data support previous assumptions of dominant inheritance. RE is likely an expression of the interaction of several loci, one of which predisposes to CTS.