Investigators at the Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London, and other centers in the UK and Europe conducted a genome-wide association study in 1018 people with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis and 7552 control subjects, with (n=757) and without (n=803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for MTLE with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3. No genetic association with febrile seizures was found in a cohort of 172 individuals with febrile seizures who did not develop epilepsy during follow-up to age 13 years. The findings suggest SCN1A involvement and common genetic variation in the epilepsy syndrome of MTLE, hippocampal sclerosis with febrile seizures. [1]

COMMENT. In addition to MTLEHS + FS, genetically-determined, epilepsy syndromes in which febrile seizures are a prominent feature include Dravet syndrome, and genetic epilepsy with febrile seizures plus. The authors suggest that focusing on clinically recognized syndromes or constellations [2] could reduce heterogeneity before genomic analyses and lead to discovery of more narrowly-defined syndromes. Genetic association studies should uncover the cause of some epilepsies and facilitate prevention or a cure.

TNK2 mutations in severe autosomal recessive infantile onset epilepsy with intellectual disability. The proband, a girl, presented at age 19 months with focal seizures resembling MTLE, and characterized by unresponsiveness, hypertonia, automatisms and secondary generalization. Seizures recurred several times a day and were refractory to medication. Birth and early development were normal, and cognitive regression with autistic features occurred soon after seizure onset. MRI was normal. Video-EEG recording and PET scan showed right anteromedial temporal lobe seizure onset, but temporal lobectomy at age 4.5 years failed to control seizures. The resected tissue showed no abnormality. Two younger brothers had a similar history to that of the proband. The cognitive regression with absence of myoclonus, normal MRI, and unremarkable interictal EEG distinguish this phenotype from known infantile onset epileptic syndromes and encephalopathies. The phenotype in this small family is a consequence of a homozygous mutation in the TNK2 gene, resulting in a gain of function. [3]