The STXBP1 gene is located on chromosome 9q34.1. STXBP1-encephalopathies are caused by a variety of mutations (changes) in the STXBP1 gene. Usually patients have a unique mutation (‘spelling mistake’) within the gene, although sometimes the same mutation has been found in several (unrelated) patients (see https://stxbp1.cncr.nl/). Instead of ‘spelling mistakes’, some patients are missing one copy of the STXBP1 gene (or a smaller fraction of the gene) in their DNA. This is called a deletion. At this moment, clinicians cannot predict the severity of the condition in an individual patient based on the type of mutation (genotype- phenotype correlation).
The STXBP1 gene carries the code for the STXBP1 protein, also known as the syntaxin-binding protein 1 or MUNC18-1. This protein is very important for proper functioning of the brain cells (neurons). Mutations in STXBP1 most likely cause lower STXBP1 protein levels, leading to impairment of the communication between the neurons (see https://stxbp1.cncr.nl/stxbp1_disorders). Further research is needed for better understanding of these mechanisms.
STXBP1 mutations are discovered through DNA-testing. This is usually carried out in children with seizures and/or developmental abnormalities. Because of the wide clinical variability and overlap with similar conditions, instant diagnosis of STXBP1-E is rare. Usually the diagnosis is based on the result of DNA-testing carried out of multiple genes in parallel, for example through a next-generation sequencing (NGS) panel or whole-exome sequencing. In some patients, the diagnosis is made after microarray analysis of the chromosomes (deletion of (part of) the gene).