Electroclinical picture of autosomal dominant nocturnal frontal lobe epilepsy in a Japanese family

Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first described partial epilepsy syndrome known to be due to a single gene mutation. We found a first Japanese ADNFLE family with a novel mutation of the neuronal nicotinic acetylcholine receptor (nAChR) alpha 4 subunit (CHR NA4) gene. The aim of this report is precisely to describe the electroclini cal manifestations of ADNFLE in this family and to compare these findings w ith those of other families reported previously in the literature. Methods: Three affected family members were investigated electroclinically by close clinical observation, interictal EEG, video-EEG monitoring, magnet ic resonance imaging, and single-photon-emission tomography. Information ab out other affected family members was obtained from either the spouse or th e parents. Mutations within the CHRNA4 gene were examined in seven family m embers. Results: The clinical manifestations and diagnostic findings in the members of this family were consistent with ADNFLE. However, there were intrafamil ial and interfamilial variations in clinical features. The seizures of the patients were brief tonic seizures, with hyperventilation in children and s econdarily generalized tonic-clonic convulsions in adults. The onset of the children's seizures began in infancy and early childhood. The children's s eizures were sometimes provoked by movement and sound stimulation, and did not respond to antiepileptic drugs, On the other hand, the adults' seizures disappeared spontaneously or were easily controlled with carbamazepine. Th ree children showed hyperactivity, and two children had mild mental retarda tion. All patients had impaired consciousness during their seizures and no auras. A novel missense mutation (c755C>T) in exon 5 of the CHRNA4 gene was found in four affected family members. Conclusions: The electroclinical pictures of a Japanese family with ADNFLE were basically the same as those of other families reported, but with sligh t differences. ADNFLE is probably not uncommon, and it is very likely that there are unidentified patients with this inherited disorder in Japan.