PURPOSE: Dominant mutations in the STXBP1 gene are a recently identified cause 
of infantile epileptic encephalopathy without metabolic and structural brain 
anomalies. To date, 25 patients with heterozygous mutation or deletion of STXBP1 
have been reported. A diagnosis of early infantile epileptic encephalopathy with 
suppression-burst (Ohtahara syndrome) was made in most of them, with infantile 
spasms and nonsyndromic infantile epileptic encephalopathy being the diagnosis 
in other patients. Although the phenotypic spectrum of STXBP1-related 
encephalopathy is emerging with evidence suggesting the relatively frequent 
involvement of this gene in infantile epileptic encephalopathies, accurate 
clinical descriptions of patients are still necessary to delineate this entity.
METHODS: The sequence of the STXPB1 gene was analyzed in 29 patients with early 
onset syndromic or nonsyndromic infantile epileptic encephalopathy without brain 
magnetic resonance imaging (MRI) anomalies and with normal chromosomal and 
metabolic checkup. Another patient with a complex phenotype was analyzed by 
comparative genomic hybridization (CGH) array.
KEY FINDINGS: From the studied series, 2 of 29 patients were found to carry a de 
novo heterozygous mutation in STXBP1. One patient carried the recurrent 
p.Arg406His mutation and the other an insertion of 10 bases leading to a 
premature termination codon. CGH array experiment detected a deletion of 3-3.5 
Mbp in the third patient with infantile epileptic encephalopathy and nail 
malformations. All three had infantile spasms associated with partial seizures 
that responded to antiepileptic drug therapy. Intellectual abilities were 
severely impaired in all of them. Generalized tremor was the main neurologic 
striking feature in the three patients, with one of them further displaying 
unilateral akinetic-hypertonic syndrome.
SIGNIFICANCE: Mutations in STXBP1 are relatively frequent in patients with 
infantile epileptic encephalopathies. STXBP1-related encephalopathy may present 
as drug-responsive infantile spasms with focal/lateralized discharges. 
Generalized tremor appearing after the first year of life may be a clue to the 
diagnosis in some patients.