Abstracts

Rationale: Autosomal dominant epilepsy with auditory features (ADEAF) is characterized by seizures suggesting a lateral neocortical temporal lobe origin. Affected subjects typically experience auditory or aphasic symptoms. Less frequently other sensory, motor, psychic and autonomic symptoms occur. Brain imaging is considered to be unremarkable. However, temporal lobe malformations were previously identified in one family by high-resolution MRI. Mutations in the LGI1 gene have been identified in about one third of the families. The genetic cause in the other families is unknown. Here, we report a new ADEAF family that included one family member who underwent epilepsy surgery due to a right temporal lesion. We aim to clarify if MRI abnormalities are part of the phenotypic spectrum of ADEAF and identify the molecular cause in this family.Methods: A large Iranian Jewish family including 14 individuals with epileptic seizures over 3 generations was recruited and phenotyped. Linkage analysis was performed using SNP genotyping microarrays. Subsequently, all exons of LGI1 were Sanger sequenced.Results: Phenotypic information was available in 11 individuals whose seizure semiology was consistent with ADEAF. Auditory auras were reported by 4 individuals, visual auras by 2 and the proband reported vertiginous auras. Four family members had generalized tonic-clonic seizures without focal features. MRI was performed in two affected individuals. A right mesiotemporal tumor most consistent with low-grade glioma was present in the proband. He underwent epilepsy surgery and pathology revealed focal cortical dysplasia (FCD) type IIA. One other individual had a meningeoma in the cerebellopontine angle but no epileptogenic lesion was identified on MRI. Linkage analysis categorizing the individual with FCD as unknown revealed two peaks, one at chromosome 9p24 (LOD score 2.43) and one at chromosome 10q22-25 (LOD score 2.04). As the region on chromosome 10 included LGI1 this gene was sequenced and a heterozygous mutation in exon 6 (c.641T>C, p.214L>P) was identified in all available affected family members except for the proband.Conclusions: Genotyping in this large ADEAF family identified a new LGI1 mutation and confirmed that the individual with the right temporal lesion is a phenocopy. Our findings corroborate that the phenotypic spectrum of ADEAF does not include focal cortical dysplasia. Careful phenotyping and the identification of potential phenocopies is paramount for gene identification in epilepsy families.