[Autosomal dominant nocturnal frontal lobe epilepsy. An electroclinical and genetic description of a Norwegian family with ten affected members].
We describe a Norwegian family with clusters of brief nocturnal motor seizures with hyperkinetic or tonic manifestations. Seizures started in childhood. Neurological examination and neuroimaging were normal. Interictal EEG registrations were mostly normal, ictal EEG registrations disclosed left frontal epileptiform discharges in two of three patients examined and just shallow arousal preceding the attack in one of the three patients. Segregation analysis indicated an autosomal dominant inheritance pattern, and the patients were subsequently diagnosed as having autosomal dominant nocturnal frontal lobe epilepsy, a disorder first described in 1995. A missense mutation in the gene for the alpha-4 subunit of the neuronal nicotinergic acetylcholine receptor was recently described in an Australian family with this disorder. Our Norwegian family proved to have a novel insertion mutation (776ins3) in the same gene. This mutation affects the second transmembrane domain (M2) which forms the critical section of the ion channel. This is the first case of idiopathic partial epilepsy where the underlying molecular defect has been found. The fact that a dysfunction of the nicotinergic acetylcholine receptor may give rise to frontal epileptic seizures was surprising and may shed new light on the basic mechanisms of epileptogenesis. Manipulations of the cholinergic system may open up a new therapeutic approach.
Nakken
K O
KO
Statens senter for epilepsi, Sandvika.
Magnusson
A
A
Steinlein
O K
OK
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D011950:Receptors, Cholinergic / Q000235:genetics; D012890:Sleep
D011950:Receptors, Cholinergic
Autosomal dominant nattlig frontallappsepilepsi. En elektroklinisk og genetisk beskrivelse av en norsk familie med ti affiserte medlemmer.