Abstracts

Rationale: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an idiopathic focal epilepsy syndrome with auditory symptoms or receptive aphasia (ASRA) as prominent ictal manifestations. These symptoms suggest localization of the epileptogenic zone to the lateral temporal lobe; hence the syndrome has also been called autosomal dominant lateral temporal lobe epilepsy (ADLTE). The occurrence of ASRA in ?2 affected family members has been used as a simple definition of ADPEAF, and mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been found in up to 50% of families meeting this definition. Refinement of the syndrome definition is important to improve identification of families likely to carry LGI1 mutations and facilitate selection of families for identification of new ADPEAF susceptibility genes. Methods: We used an epidemiologic approach to refine syndrome definition in ADPEAF by comparing focal seizure symptoms in ADPEAF families with and without LGI1 mutations. To distinguish ADPEAF from other forms of familial temporal lobe epilepsy, we focused on symptoms characteristic of mesial temporal lobe (MTL) seizure onset: visceral/epigastric sensations, fear, d j -vu, olfactory auras, and oral and limb automatisms. The study population comprised 112 subjects with idiopathic focal epilepsy from 30 families containing ?2 individuals with ASRA, 11 of which had LGI1 mutations. We compared occurrence of MTL symptoms in families with and without mutations, first in all individuals with focal epilepsy and then in individuals with ASRA specifically (N=89). We used generalized estimating equations to account for within-family correlations. Results: The two sets of families were similar with respect to sex, ethnicity, education, age at onset, and number of individuals with ASRA. Among all individuals with focal epilepsy, the proportion of individuals with MTL symptoms did not differ between families with and without mutations. Among individuals with ASRA, however, the proportion with MTL symptoms was lower in families with LGI1 mutations than in those without (29% vs. 55%, p=0.049). This difference was attributed to a lower proportion with visceral/epigastric symptoms among individuals with ASRA in the mutation families vs. the non-mutation families (10% vs. 32%, p=0.017). The specific types of auditory symptoms also differed between the two groups of families: individuals with ASRA were less likely to have auditory distortions in the mutation families than in the non-mutation families (17% vs. 52%, p=0.002). Conclusions: These findings suggest that individuals with ASRA have different symptom profiles in families with vs. without LGI1 mutations. The higher frequency of visceral/epigastric symptoms in the non-mutation families suggests that some of these families may have more MTL involvement. The occurrence of ictal auditory symptoms or receptive aphasia in ?2 affected members with focal epilepsy may be insufficient to define ADPEAF. Ruling out MTL seizure symptoms may better facilitate identification of families likely to have LGI1 mutations.