OBJECTIVES: Heterozygous mutations in STXBP1, encoding the syntaxin binding 
protein 1, have recently been identified in Ohtahara syndrome, an epileptic 
encephalopathy with very early onset. In order to explore the phenotypic 
spectrum associated with STXBP1 mutations, we analyzed a cohort of patients with 
unexplained early-onset epileptic encephalopathies.
METHODS: We collected and clinically characterized 106 patients with early-onset 
epileptic encephalopathies. Mutation analysis of the STXBP1 gene was done using 
sequence analysis of the exon and intron-exon boundaries and multiplex 
amplification quantification to detect copy number variations.
RESULTS: We identified 4 truncating mutations and 2 microdeletions partially 
affecting STXBP1 in 6 of the 106 patients. All mutations are predicted to 
abolish STXBP1 function and 5 mutations were proven to occur de novo. None of 
the mutation-carrying patients had Ohtahara syndrome. One patient was diagnosed 
with West syndrome at disease onset, while the initial phenotype of 5 further 
patients did not fit into a specific recognized epilepsy syndrome. Three of 
these patients later evolved to West syndrome. All patients had severe to 
profound mental retardation, and ataxia or dyskinetic movements were present in 
5 patients.
CONCLUSION: This study shows that mutations in STXBP1 are not limited to 
patients with Ohtahara syndrome, but are also present in 10% (5/49) of patients 
with an early-onset epileptic encephalopathy that does not fit into either 
Ohtahara or West syndrome and rarely in typical West syndrome. STXBP1 mutational 
analysis should be considered in the diagnostic evaluation of this challenging 
group of patients.