The millennium variant – SCN1B, gene validity, and GEFS+

800 years. The discovery of SCN1B as a causative gene for Genetic Epilepsy with Febrile Seizures Plus (GEFS+) was one of the most pivotal moments in epilepsy genetics. This discovery not only shaped our understanding of the channelopathy concept, but also highlighted the importance of careful phenotyping. Therefore, it may be surprising that SCN1B took almost a quarter of a century to accrue sufficient evidence to be considered as a definite epilepsy gene. However, this is not the only aspect where SCN1B operates on its own time scale. In a recent publication, one of the most common disease variants in SCN1B could be traced back more than 800 years to a single founder event. Here is a 2023 update on the journey of one of the most well-known but also most mysterious epilepsy genes whose origins are lost in the depth of time. Continue reading

Heat at the synapse – STX1B mutations in fever-associated epilepsies

Febrile Seizures. The discovery of the genes for fever-associated epilepsies was one of the most relevant milestones in epilepsy genetics. Discovery of the underlying genes including SCN1A, SCN1B and GABRG2 was tightly linked to the development of the Genetic/Generalized Epilepsy with Febrile Seizures Plus (GEFS+) concept, describing the spectrum of epilepsy phenotypes seen in families with these mutations. Gene discovery in GEFS+, however, has slowed down in recent years, and no further causative genes had been identified for more than a decade. Now, in a recent paper in Nature Genetics, mutations in STX1B are found as a novel cause for fever-associated epilepsies. Continue reading

The top three publications in epilepsy genetics 25 years ago

Looking back. In this week’s ILAE Genetics Commission post, we would like to look 25 years back and examine the most important publication in the field in 1989, the year the Berlin wall fell. What concepts did we have back then and how did our understanding of epilepsy and genes change? Here are the top three publications of 1989. Continue reading