Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation

Aims. Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. Methods. We studied the proband and her mother by means of EEG, video-EEG, 3T MRI, FDG-PET and genetic testing. Results. Both patients had a focal drug-resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic-clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG-PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. Conclusion. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug-resistant epilepsy associated with mild MRI temporal changes.