Main clinical features
Mutations in the STXBP1 gene are among the most prevalent causes of early infantile epileptic encephalopathy (EIEE). Key phenotypic abnormalities include (often refractory) seizures, developmental delay, intellectual disability (ID) and movement disorders. Other possible features are feeding difficulties, autism spectrum disorder (ASD) and severe speech delay. The disorder caused by STXBP1 mutations is often referred to as STXBP1-encephalopathy (STXBP1-E).
A more extensive description of the clinical spectrum of STXBP1 mutations can be found in the section Professionals – Clinical characteristics.
Prevalence
STXBP1 mutations are rare. Due to a very limited number of cases (+/-230) identified so far, it is difficult to predict the prevalence of the disorder. Stamberger et al. (2016) estimated a frequency of STXBP1 mutations of approximately 1 per ninety thousand births in a Danish cohort. A more recent study by Uddin et al. (2017) calculated that STXBP1 mutations are found in 3% of clinically identified epilepsy cases. More studies are needed for a more accurate estimation of the frequency of STXBP1 mutations.
Inheritance
STXBP1 mutations are inherited in an autosomal dominant manner. To date, nearly all reported cases result from a de novo mutation. Thus, most affected individuals represent simplex cases, i.e. a single occurrence in a family. The recurrence risk for future pregnancies is low (probably <1%), but greater than that of the general population, because of the possibility of germline mosaicism in one of the parents. There has also been one case report of an unaffected parent carrying a mosaic STXBP1 mutation (Saitsu et al., 2011).