Guilt by association: SCN1A in Temporal Lobe Epilepsy

GWAS. Genome-wide association studies investigate the association of common genetic variants with disease in large patient samples. While this approach has been very successful in many other diseases, the results in epilepsy research have been less convincing. Given the complexity of epilepsy phenotypes, selection of the right epilepsy phenotype has been an ongoing debate. Now, a recent study in Brain finds an intronic variant of the SCN1A gene that is associated with Temporal Lobe Epilepsy (TLE), the most common epilepsy in man. Interestingly, the association with SCN1A seems to be specific for only a particular subtype of focal epilepsies. Continue reading

Familial Partial Epilepsy with Variable Foci and mutations in DEPDC5

A long story, a complicated phenotype. Massive parallel sequencing technologies were an innovation in neurogenetics and made the discovery of many genes underlying familial epilepsies possible. However, some epilepsy syndromes turned out to be more “stubborn” than others. Now, in a back-to-back submission in Nature Genetics, two groups report on the gene underlying Familial Partial Epilepsy with Variable Foci (FPEVF). And no, it’s not an ion channel this time. Continue reading

What’s the Frequency, Kenneth? The story of LGI1

Can’t you hear the radio?  “S.W. was spending an afternoon at this girlfriend’s house when he suddenly heard a radio sound in his right ear.  He asked his girlfriend whether she was aware of this sound as well, but he could not understand her answer. S.W. then lost consciousness and convulsed. He presented with a second seizure several months later. S.W. was started on carbamazepine and remained seizure-free. Interestingly, his mother had seizures starting at the same age. Furthermore, his sister had her first seizure at the age of 8 years and frequently reported auras where she would see colourful pictures and hear noises like a familiar song. These episodes sometimes occurred seconds before she had a generalised tonic-clonic seizure.”

LG-what?  This impressive case report taken from Steven Waxman’s Molecular Neurology illustrates a family with lateral temporal lobe epilepsy (LTLE), a rare form of seizure disorder in which auditory features often precede a generalized tonic-clonic seizure. Auditory or acoustic features including radio sounds, machine noises or more complex acoustic phenomena arise from the lateral temporal lobe, a part of the brain important for auditory processing. During a discussion with one of our students last week, I realised that even though we frequently write about microdeletions and novel gene findings on the EuroEPINOMICS blog, some of the classics of epilepsy genetics may sometimes be revisited as well. LTLE is the premier example that genetic epilepsies are not neccesarily due to ion channels. Continue reading