Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families.
Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.
Picard
F
F
INSERM U 398, Clinique Neurologique, Strasbourg, France. Fabienne.Picard-Kieny@hcuge.ch
Baulac
S
S
Kahane
P
P
Hirsch
E
E
Sebastianelli
R
R
Thomas
P
P
Vigevano
F
F
Genton
P
P
Guerrini
R
R
Gericke
C A
CA
An
I
I
Rudolf
G
G
Herman
A
A
Brice
A
A
Marescaux
C
C
LeGuern
E
E
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005060:Europe; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010375:Pedigree; D017354:Point Mutation; D011978:Receptors, Nicotinic / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human