Glut1 deficiency and Myoclonic Astatic Epilepsy – reassessed

Ketogenic. Several patients with Myoclonic Astatic Epilepsy (MAE) have a surprisingly positive response to the ketogenic diet, even after failing several antiepileptic medications. Given this observation, it is obvious to assume that SCL2A1 mutations play a significant role in MAE, and some earlier studies seemed to suggest that up to 5% of MAE patients carry SLC2A1 mutations. However, in a recent study, we failed to demonstrate a connection between SLC2A1 mutations and Myoclonic Astatic Epilepsy (MAE) in a large cohort of patients. Read more on why the genetics of MAE is an ongoing mystery and why we need a new approach to “keto-genetics”. Continue reading

An inconvenient truth – segregation of monogenic variants in small families

Climate change. In the era of exome and genome sequencing, it might be worthwhile revisiting the merit of family studies in epilepsy research. Seizure disorders are known to have a highly diverse genetic architecture. When singleton studies identify a single, unique gene finding, this discovery usually does not provide much information about the potential causal role of the variant given the high degree of genomic noise. In contrast, family studies are usually considered more robust, as segregation of variants can be traced. Here is the inconvenient truth: unless the family is very large, segregation of possibly monogenic variants adds little information given the vast amount of variants present in our genomes. Continue reading

Traveling with Lennox – the petit mal triad

Lights on and lights out. Staring spells, petits mals, pyknolepsy and absence seizures. The brief spells that occur in patients with epilepsy have riddled neurologists for centuries. This became clear to me when Zaid Afawi and myself saw an epilepsy family in the West Bank on Sunday. When are staring spells epileptic and what kind of seizures are they? For me, this was a good opportunity to read Lennox’s thoughts on this. Eventually, after a long day under the Middle Eastern sun, I fell asleep over the chapter on absence status. Continue reading