Epilepsy: Generalized Epilepsy with Febrile Seizures Plus, Type 9 via the STX1B Gene

Generalized epilepsy with febrile seizures plus, type 9 is a fever-associated epilepsy syndrome characterized by episodes of febrile seizures around age 3. However, afebrile seizures also occur. The disorder shows high phenotypic variability with different type of seizures including generalized tonic-clonic, atonic, myoclonic, complex partial and absence. In some patients, developmental delay has been noted (Schubert et al. 2014. PubMed ID: 25362483; Kearney. 2015. PubMed ID: 26316853).

Generalized epilepsy with febrile seizures plus, type 9 is inherited in an autosomal dominant manner and is caused by pathogenic variants in the STX1B gene. STX1B encodes syntaxins which is a presynaptic protein involving in regulation of synaptic vesicle exocytosis and the releasable pool in central synapses (Schubert et al. 2014. PubMed ID: 25362483; Mishima et al. 2014. PubMed ID: 24587181). The reported pathogenic variants include missense, nonsense, small framshift deletion/duplication, small indel variants, as well as a large deletion (Human Gene Mutation Database).

Generalized epilepsy with febrile seizures plus is clinically and genetically heterogeneous. Clinical sensitivity for STX1B cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because all pathogenic variants reported are detectable by sequencing.

This test provides full coverage of all coding exons of the STX1B gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.