Epilepsy, Partial, With Pericentral Spikes

Clinical Features

In an extensive Brazilian kindred of Portuguese extraction, Kinton et al. (2002) observed a familial epilepsy syndrome, which they designated partial epilepsy with pericentral spikes (PEPS). Affected members in the family reported by Kinton et al. (2002) manifested a variety of seizure types, including hemiclonic, hemitonic, generalized tonic-clonic, simple partial (stereotyped episodes of epigastric pain), and complex partial seizures consistent with temporal lobe epilepsy. The syndrome was benign, either requiring no treatment or responding to a single antiepileptic medication. Seizure onset was in the first or second decade of life, with seizures in individuals up to the age of 71 years and documented encephalogram changes up to the age of 30 years. A key feature of PEPS was a characteristic encephalogram abnormality of spikes or sharp waves in the pericentral region (centroparietal, centrofrontal, or centrotemporal). The distinctive encephalogram abnormality of pericentral spikes united the several seizure types into a discrete epilepsy syndrome. The inherited nature of the syndrome could be overlooked because of the variability in penetrance and seizure types among affected family members.

Inheritance

The pedigree pattern in the family with PEPS reported by Kinton et al. (2002) was consistent with autosomal dominant inheritance, with vertical and male-to-male transmission. There was evidence of incomplete penetrance, both for the EEG trait and epilepsy, with obligate gene carriers remaining unaffected up to ages 66 and 70 years, respectively.

Mapping

By linkage studies, Kinton et al. (2002) mapped the epilepsy in the Brazilian family to 4p15 with a maximum lod score of 3.3 at D4S2311. Haplotype analysis confirmed the boundaries of the critical region. Homozygosity for the haplotype was not associated with a more severe phenotype.

Molecular Genetics

For discussion of a possible role of variation in the METTL19 gene in PEPS, see 614309.0001.