Epilepsy, Familial Temporal Lobe, 8

A number sign (#) is used with this entry because of evidence that familial temporal lobe epilepsy-8 (ETL8) is caused by heterozygous mutation in the GAL gene (137035) on chromosome 11q13. One such family has been reported.

For a discussion of genetic heterogeneity of temporal lobe epilepsy, see ETL1 (600512).

Clinical Features

Guipponi et al. (2015) reported a pair of monozygotic twin brothers who developed temporal lobe epilepsy at age 13 years. Both reported aura variably characterized by abdominal discomfort, incoherent speech, blurred vision, auditory hallucinations, slow ideation, or deja vu. The symptoms were consistent with complex partial seizures with occasional secondary generalization. Brain MRI was normal. Both patients responded well to antiepileptic medication.

Molecular Genetics

In 2 monozygotic male twins with ETL8, Guipponi et al. (2015) identified a de novo heterozygous missense mutation in the GAL gene (A39E; 137035.0001). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. In vitro functional studies showed that the mutant protein had antagonistic activity against GALR1 (600377)-mediated responses as well as decreased binding affinity and reduced agonist properties for GALR2 (603691). These findings suggested that the mutant protein could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to epilepsy. Sequencing of the GAL gene in a cohort of 582 additional patients with epilepsy did not identify any mutations.