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Infantile Epilepsy: Ohtahara Syndrome - STXBP1

Early infantile epileptic encephalopathy with suppression-burst (EIEE)

Clinical Features

Mutations in STXBP1 have been identified in up to 30% of patients with early-onset epileptic encephalopathy classified as Ohtahara Syndrome. However, recent studies indicate that the clinical spectrum of STXBP1 mutations is broader and that they may account for up to 10 % of early-onset epileptic encephalopathies.

Ohtahara Syndrome is a relatively rare, severe epilepsy syndrome. Epileptic seizures are observed in all patients beginning in the first three months; in most cases, seizures are observed in a patient's first few weeks. Seizures are at first short, generalized, and tonic (infantile spasms; therapy resistant). Some patients may initially show focal or asymmetric tonic seizures as well; myoclonias are rare. Characteristic of the disease is the so-called "suppression-burst" pattern seen in EEGs; typical clinical progression is from West Syndrome in infancy (3 to 6 months) to Lennox-Gastaut Syndrome at 1 to 3 years of age. The prognosis is not good; the disease is marked by severe developmental delay and a relatively high childhood mortality rate.

Genetic Information

Ohtahara Syndrome may be caused by a metabolic disorder or frequent structural deformities of the brain. However, some patients with Ohtahara Syndrome have recently been found to carry mutations in the STXBP1 gene located on chromosome 9 (9q34.1; Saitsu-H, et al. Nature Genetics 40 (6) 2008). The coding STXBP1 (syntaxine binding) protein plays an essential role in synaptic vesicle release and neurotransmitter secretion. Cases are normally sporadic, based on a dominant new mutation in the STXBP1 gene.
Specifically male patients with Ohtahara Syndrome have also been found to carry pathogenic mutations in the X-linked ARX gene (see information on ARX-associated diseases).

Diagnostic