Somatic mosaicism of SLC35A2 in focal epilepsy: an emerging common genetic mechanism

Somatic mosaicism in focal epilepsy. Recent findings highlighted the role of somatic parental mosaicism in epileptic encephalopathies. However, somatic mosaicism has also emerged over the last few years as a prominent mechanism in the pathogenesis of lesional focal epilepsies, including focal cortical dysplasia (FCD) type 2 and hemimegalencephaly. Previous studies have identified the role of mosaicism of genes such as MTOR, TSC1/TSC2, and genes encoding components of the PI3K/AKT pathway in patients with epilepsy secondary to brain malformations. A recent study in Annals of Neurology has identified a new unrelated genetic cause of refractory non-lesional focal epilepsy, which leads us to wonder what role mosaicism may be playing in focal epilepsies without obvious findings on MRI.
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The tale of two planets: the expanding spectrum of STXBP1

Intergalactic, planetary. At the end of last year, I gave a presentation on epilepsy genetics for epilepsy surgeons. Having worked in presurgical epilepsy monitoring myself for some time, I could not help realizing that the fields of epilepsy surgery and epilepsy genetics are quite distinct. Both fields use different terminologies and different concepts and virtually represent parallel worlds. In the vast majority of cases, this does not really matter as there is little overlap between the patients undergoing epilepsy monitoring for later surgery and patients where a genetic etiology is assumed. In a recent paper in Epilepsia, the case of a patient with an STXBP1 mutation is presented who successfully underwent epilepsy surgery. So who is right when both fields collide while treating a single patient? Continue reading