STXBP1-related disorders: deciphering the phenotypic code

STX. Neurodevelopmental disorders due to disease-causing variants in STXBP1 are amongst the most common genetic epilepsies with an estimated incidence of 1:30,000. However, despite representing a well-known cause of developmental and epileptic encephalopathies in the first year of life, relatively little has been known about the overall genetic landscape and no genotype-phenotype correlations have been established. In our recent publication including almost 20,000 phenotypic annotations in 534 individuals with STXBP1-related disorders, we dive deep into the clinical spectrum, examine longitudinal phenotypes, and make first attempts at assessing medication efficacy based on objective information deposited in the Electronic Medical Records (EMR), including information from the almost 100 “STXers” seen at our center in the last four years. Continue reading

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