STXBP1 mutations are characterized by a variety of neurodevelopmental features. The disorder caused by STXBP1 mutations is often referred to as STXBP1-encephalopathy (STXBP1-E).
Seizures
Epilepsy is reported in approximately 95% of patients with STXBP1-E. The onset tends to be early in life, with a median onset around 6 weeks, but possible onset up to 13 years of age. Most frequent seizure types are epileptic spasms, focal seizures and tonic seizures. A substantial fraction of patients is diagnosed with an epilepsy syndrome such as Ohtahara or West syndrome. EEG recordings may reveal focal or multifocal epileptic activity, a burst-suppression pattern and/or hypsarrhythmia. Newly diagnosed patients often encounter difficulty with seizure control (see section Professionals – Management).
Developmental delay/ intellectual disability
Frequent epileptic activity contributes to the cognitive and behavioral impairment in STXBP1-E patients. However, developmental delay is also reported in patients prior to the identification of seizures as well as in (the minority of) patients who don’t present seizures. Most patients have severe to profound intellectual disability. This includes for example a delay in acquisition of walking ability (until 6 years of age in some patients) and severe speech impairment or even absence of speech. A minority of patients is reported to have developmental regression, not necessarily related to the onset of seizures, as reviewed by Stamberger et al. (2016).
Behavioral disorders
The behavioral symptoms of STXBP1-E patients may consist of an autism spectrum disorder (ASD) or autistic features, such as stereotypical behavior. Therefore, some patients are initially suspected of a Rett syndrome phenotype. Other behavioral difficulties reported in a smaller number of patients include hyperactivity and aggressive behavior.
Movement disorder
Ataxia is the most frequent movement disorder in STXBP1-E. Other possible signs in this category include tremor, spasticity, dyskinesia and dystonia.
Other features
Hypotonia can be observed in some STXBP1-E patients. Feeding difficulties are also relatively common, sometimes accompanied by failure to thrive. Structural brain abnormalities can be present in roughly half of the patients, but are not specific to the diagnosis. A small number of patients present with microcephaly.