Dominant partial epilepsies: A clinical, electrophysiological and genetic study of 19 European families

Abstract

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.

Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31

“…EEGs were interpreted by two independent clinical neurophysiologists who were blind to the status of individuals. Focal epileptiform EEG abnormalities were defined as previously described 23 and non-epileptiform abnormalities as intermittent slow waves consistently located over the same area. MRI (1.5 Tesla unit) was performed in 5 of 9 affected members.…”

“…A disease allele frequency of 0.0001 and a penetrance of 70% were estimated using a method previously described. 23 Simulations, with the abovementioned parameters, gave a maximum pairwise lod score of 3.1 at ϭ 0.0 with a 5 allele marker of equal frequency. A whole genome scan, excluding chromosome X, was performed assuming equal frequencies for the alleles observed in the family.…”

Ion channels and epilepsy

“…Ictal video-electroencephalographic studies revealed partial seizures originating from the frontal lobe. The onset is usually in childhood, inheritance is autosomal dominant, and the penetrance approximately 70±80% Picard et al, 2000]. ADNFLE has often been misdiagnosed as paroxysmal nocturnal dyskinesia, sleep disorders such as night terrors or nightmares, or hysteria [Scheffer et al, 1994].…”

Genetic Epilepsy Syndromes Without Structural Brain Abnormalities: Clinical Features and Experimental Models

“…Paroxysmal arousals, dystonia-like attacks, and epileptic nocturnal wanderings are also part of the phenotype [120]. Ictal video-EEG studies have revealed partial seizures originating from the frontal lobe, but also from parts of the insula and temporal lobe, suggesting a defect of a broader network [121,122]. A mutation in the gene CHRNA4, encoding the α4-subunit of a neuronal nicotinic acetylcholine receptor (nAchR), was the first ion channel mutation found in an DS Dravet syndrome; ID intellectual disability; IS infantile spasms;…”