Monogenic epilepsies due to mutations of genes that do not code for ion channels: autosomal dominant lateral temporal epilepsy

Autosomal dominant lateral temporal epilepsy (ADLTE) is a well defined, albeit rare, condition, characterized by onset in adolescence or early adulthood, lateral temporal seizures with prominent auditory auras sometimes triggered by external noises, normal conventional magnetic resonance imaging, good response to antiepileptic treatment, and a benign outcome overall. The same phenotype is shared by sporadic or familial cases with complex inheritance. Missense or truncating mutations in the LGI1 gene are found in about 50 per cent of ADLTE families and 2 per cent of sporadic cases. These mutations are associated with a rather homogeneous phenotype and appear to prevent secretion of mutant proteins by transfected culture cells, suggesting a loss of function effect of mutations. LGI1 shows no homology with known ion channel genes. Recent findings suggest that LGI1 may exert multiple functions, but it is not known which of them is actually related to lateral temporal epilepsy.