About STXBP1-Related Disorders

STXBP1-related disorders were discovered in 2008 in studies of some patients with Ohtahara Syndrome, a severe early onset epilepsy. Since this initial discovery, our understanding of STXBP1-related disorders has expanded, revealing a range of patient symptoms.

Changes in the STXBP1 gene impair communication between neurons, specifically the vesicular release of neurotransmitter along the synapses. These changes are typically new in families and a single copy of a damaged gene is enough to cause the disorder. The estimated incidence rate for STXBP1-RD is ~1:30,000, and STXBP1 was recently identified as one of the five most common genes for epileptic encephalopathies and related neurodevelopmental disorders.

Common Symptoms of STXBP1-related disorders

Seizures impact 85 - 90% of patients, and may present as early as the first day of life. Common seizure types include neonatal seizures, infantile spasms, tonic, and clonic seizures. STXBP1-RD is not solely a seizure disorder. Patients may present with a broad range of symptoms including:

• Seizures

• Global Delays and/or intellectual disability

• Speech and communication issues

• Movement disorders including ataxia or tremors

• Hypotonia (decreased muscle tone)

• Spasticity (increased muscle tone)

• Feeding difficulties

• Behavior issues including repetitive behaviors or autism

• GI issues including constipation

Diagnosis

STXBP1-RD diagnosis is made through genetic testing using an Epilepsy, Neurodevelopmental or Autism/Intellectual Disability Panel; Whole Exome or Whole Genome test; or rarely chromosomal microarray analysis. If you are looking for genetic testing, apply to Probably Genetic’s free, HIPAA-compliant whole exome sequencing program here.

Treatment

Current treatment focuses on managing symptoms, and varies based on patient symptoms and co-existing disorders. Because patients with STXBP1-RD have a wide range of symptoms and functional challenges, they are best followed by a multi-disciplinary team. Antiepileptic drugs (AEDs) are used to treat seizures. For some, multiple AEDs are needed for adequate seizure control but approximately 25% of patients will not gain seizure control with AEDs. Ketogenic diet may be effective to control seizures in some patients*. A Vagus Nerve Stimulation(VNS) device has also been used with some patients with STXBP1-RD.

Many patients benefit from physical, occupational, feeding, speech therapies, as well as behavior therapy such as ABA. Many patients also benefit from augmentive communication devices (AAC).