PURPOSE: STXBP1 (MUNC18-1) mutations have been associated with various types of 
epilepsies, mostly beginning early in life. To refine the phenotype associated 
with STXBP1 aberrations in early onset epileptic syndromes, we studied this gene 
in a cohort of patients with early onset epileptic encephalopathy.
METHODS: STXBP1 was screened in a multicenter cohort of 52 patients with early 
onset epilepsy (first seizure observed before the age of 3 months), no cortical 
malformation on brain magnetic resonance imaging (MRI), and negative metabolic 
screening. Three groups of patients could be distinguished in this cohort: (1) 
Ohtahara syndromes (n = 38); (2) early myoclonic encephalopathies (n = 7); and 
(3) early onset epileptic encephalopathies that did not match any familiar 
syndrome (n = 7). None of the patients displayed any cortical malformation on 
brain MRI and all were screened through multiple video-electroencephalography 
(EEG) recordings for a time period spanning from birth to their sixth postnatal 
month. Subsequently, patients had standard EEG or video-EEG recordings.
KEY FINDINGS: We found five novel STXBP1 mutations in patients for whom 
video-EEG recordings could be sampled from the beginning of the disease. All 
patients with a mutation displayed Ohtahara syndrome, since most early seizures 
could be classified as epileptic spasms and since the silent EEG periods were on 
average shorter than bursts. However, each patient in addition displayed a 
particular clinical and EEG feature: In two patients, early seizures were 
clonic, with very early EEG studies exhibiting relatively low amplitude bursts 
of activity before progressing into a typical suppression-burst pattern, whereas 
the three other patients displayed epileptic spasms associated with typical 
suppression-burst patterns starting from the early recordings. Epilepsy 
dramatically improved after 6 months and finally disappeared before the end of 
the first year of life for four patients; the remaining one patient had few 
seizures until 18 months of age. In parallel, EEG paroxysmal abnormalities 
disappeared in three patients and decreased in two, giving place to continuous 
activity with fast rhythms. Each patient displayed frequent nonepileptic 
movement disorders that could easily be mistaken for epileptic seizures. These 
movements could be observed as early as the neonatal period and, unlike 
seizures, persisted during all the follow-up period.
SIGNIFICANCE: We confirm that STXBP1 is a major gene to screen in cases of 
Ohtahara syndrome, since it is mutated in >10% of the Ohtahara patients within 
our cohort. This gene should particularly be tested in the case of a surprising 
evolution of the patient condition if epileptic seizures and EEG paroxysmal 
activity disappear and are replaced by fast rhythms after the end of the first 
postnatal year.