Cause or coincidence – recessive SCN1A variants in Dravet Syndrome

Recessive epilepsies. Dravet Syndrome is one of the most prominent genetic epilepsies and presents in the first year of life with prolonged fever-associated seizures. Haploinsufficiency of SCN1A, either through mutations or deletions, is the major cause of Dravet Syndrome. In a recent publication in the European Journal of Pediatric Neurology, two families with recessive Dravet Syndrome and biallelic SCN1A variants are reported. Let’s have a look at how to interpret these findings. Continue reading

Publications of the week – Dravet Syndrome, TBC1D24, and CSTB

Issue 6/2015. Publications from the most recent issue of Epilepsia are very prominent in this week’s selection of publications. We discuss the frequency of Dravet Syndrome, a novel family with a TBC1D24 mutation, and the role of Cystatin B (CSTB) in Juvenile Myoclonic Epilepsy. Continue reading

Flickering lights, endophenotypes, and EEG genetics – CHD2 in photosensitivity

Heritable. Many epilepsy syndromes have signature EEG traits, and these traits are thought to have a strong genetic component. The endophenotype concept suggests that using these epilepsy-related traits in genetic studies will facilitate gene discovery, a concept that has failed us so far in epilepsy research, unfortunately. Now, in a recent publication in Brain, we were able to demonstrate that variants in CHD2 predispose to photosensitivity, an abnormal cortical response to flickering light. Finally, after several decades of persisting difficulties, there is some progress in the field of EEG genetics. Continue reading

USP9X, Ubiquitin, and the PRICKLE interactome

PRICKLE. There are some genes implicated in human epilepsies that we have a hard time making sense of. PRICKLE1, implicated in a recessive progressive myoclonus epilepsy, is one of these genes. In a recent publication in PLoS Genetics, the interactome of the enigmatic PRICKLE proteins is explored. The authors rediscover an almost forgotten gene implicated in intellectual disability. Continue reading

The two faces of KCNA2 – a novel epileptic encephalopathy

Delayed rectifier. The discovery of de novo mutations in ion channel genes as a cause for genetic epilepsies continues. In a recent publication in Nature Genetics, we have identified de novo mutations in KCNA2 as a novel cause of epileptic encephalopathies associated with ataxia. Interestingly, even within a single gene, two different phenotypes seem to be emerging. Continue reading

Galanin mutations in Temporal Lobe Epilepsy

Transmitted. When we think about epilepsy-related neurotransmitters, we often limit ourselves to the most prominent transmitters in the Central Nervous System, namely glutamate, GABA and to some extent acetylcholine. However, besides these classical transmitters, there are more than 100 small peptides released in the mammalian brain, which are referred to neuropeptides. Here is the story of galanin, the first neuropeptide in epilepsy genetics. Continue reading