De novo STXBP1 mutation in a child with hypotonia, intellectual disability, tremor and without epilepsy

Syntaxin-binding protein 1, encoded by STXBP1, is widely expressed in the brain and plays a critical function in regulating neurotransmitter release and synaptic vesicle fusion by binding to and altering the conformation of syntaxin-1A (STX1A). According to the previous reports, pathogenic loss-of- function mutations in this gene cause a variety of different forms of epilepsies, the majority of which occur during childhood. There may also be spasticity, dystonia, tremors, choreiform and stereotyped movements, ataxia, and hypotonia. The disease’s phenotypical spectrum remains unknown. We report here a de novo mutation (c.1162C > T: p.R388X) in exon 14 of the STXBP1 gene that causes muscular hypotonia, speech and walking delays, intellectual disability, and tremors in a 5-year-old boy. Brain magnetic resonance imaging was normal. This variant was identified as de novo (maternal and paternal confirmed). This is the first Turkish report of a patient with a truncating mutation in STXBP1 that does not show epilepsy, thus expanding the clinical spectrum associated with STXBP1 gene disorders.