Phenotypic Spectrum of STXBP1 Gene Mutations in an Emirati Case Series

Genetic mutations are increasingly recognized as etiologic factors for epilepsy and neurodevelopmental disorders. Loss of function mutations in STXBP1, one of such genes, has, in recent years, been demonstrated to cause a broad spectrum of epilepsy syndromes and chronic neurodisabilities. Syntaxin-binding protein 1 (STXBP1) is a well-recognized membrane trafficking protein responsible for synaptic transmission and is expressed ubiquitously across the brain. Our case series presents the neurodevelopmental phenotype of children with STXBP1 mutations and is the first to be reported in an Emirati patient cohort. We gathered data on five children with genetically confirmed STXBP1 mutations, each displaying varying symptomatology, EEG features, response to antiepileptic medications, and eventual disease progression. This report reveals that a majority of STXBP1 mutations were de-novo in origin; heterozygous; pathogenic to likely pathogenic variants; clinical disease onset was predominantly during infancy in the form of developmental delays with or without seizures; most of the children had co-existing ADHD or autism spectrum disorders; typical seizure semiology at onset was in the form of infantile spasms, progressing to a melange of mixed seizure types; seizure control on antiepileptic drug therapy was variable, with all cases requiring more than two medications; global developmental delay was noted in all studied children; and MRI brain findings were unremarkable in all cases. This case series demonstrates a degree of uniformity of STXBP1 mutation disease phenotypes with international literature and provides a unique insight into the genetic profile of affected children within the Emirati population.