Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24

Abstract

Purpose: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization.

Methods: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2.

Results: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (theta=0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93.

Conclusions: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway.

FIG. 1

Pedigrees of four families with autosomal dominant partial epilepsy with auditory features. Individuals with idiopathic epilepsy are denoted by solid symbols; those with symptomatic epilepsy, febrile seizures, other acute symptomatic seizures, isolated unprovoked seizures, or uncertain diagnoses are denoted by “?” and classified as unknown in the linkage analysis. Haplotypes defined by cosegregation of alleles at the seven markers D10S185, D10S200, D10S198, D10S603, D10S192, D10S222, and D10S566 on chromosome 10q are indicated by black bars. Haplotypes of individuals marrying into the family are shown as open bars, although phase cannot be assigned unambiguously. Genders have been hidden and birth orders changed to protect confidentiality.