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

Have we given up on the genetics of febrile seizures?

Fever, genes, and seizures. Undoubtedly, febrile seizures are the most common epilepsy syndrome in humans. Up to 5% of children have febrile seizures. In most children, these febrile seizures are self-limiting, and there is no recurrence. Usually, no long-term treatment is required. We know from family studies and twin studies that febrile seizures have a significant genetic component. Now here are two surprising facts: first, the genetic contribution to febrile seizures is entirely unknown. Secondly, to my knowledge, the genetic contribution to the most common epilepsy syndrome in man has not been addressed in any of the current large-scale studies. Let’s review why this is the case and why we should change this. Continue reading

Temperature rising: 17q12 microduplications and GEFS+

GEFS+, meet CNV. Microduplications at 17q12 have been identified in various neurodevelopmental disorders and in some unaffected individuals, a pattern familiar from other structural genomic variants such as microdeletions at 16p13.11 and 15q11.2. In contrast to the corresponding microdeletion, most 17q12 microduplications are inherited. This suggests that the microduplication is a risk factor, but does not fully explain the phenotype. In a recent paper in Neurology, Hardies and collaborators look at the families of 17q12 microduplication carriers with epilepsy. And this is when they noticed something strange. Continue reading