STXBP1 encephalopathy: Cannabidiol as a treatment option and expansion of the genotype-phenotype spectrum- Case reports

Introduction: STXBP1 encodes syntaxin-binding protein-1, a protein with a role in trafficking of syntaxin-1 to the synapse and synaptic neurotransmitter release. Mutations in STXBP1 are associated with a wide range of neurodevelopmental phenotypes including epilepsy, intellectual disability and movement disorders. Case series: We report 4 individuals with pathogenic variants in STXBP1, including 2 previously unreported variants, presenting with a range of severity. 1 severely affected child with refractory seizures and distressing dystonia responded well to treatment with Cannabidiol, with both seizure cessation and improvement in tone. Conclusion: STXBP1 variants are associated with significant phenotypic pleiotropy and a wide spectrum of severity. Cannabidiol may be beneficial for severely affected individuals with seizures and movement disorders that are refractory to conventional treatments.