Authors: Dorottya B. Kacsoh, University of Central Florida College of Medicine 
Alison L. Christy, MD, PhD, Providence Pediatric Neurology at St. Vincent Medical Center—Portland, Oregon
Ganna Balagura, MD, PhD, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa—Genoa, Italy  

Reviewed: May 2023 

SUMMARY 

STXBP1-related disorders are a group of rare genetic disorders. They are caused by a variation in the STXBP1 gene.  

The variation changes the way signals are sent in the brain. Brain cells send fewer signals. This causes:  

• Developmental delay  
• Epileptic encephalopathy 

Epileptic encephalopathy is a progressive decline in brain function due to frequent seizures.  

Disorder Overview

DESCRIPTION

STXBP1-related disorders present between birth and adolescence. Most children begin to develop signs around six weeks of age.  

STXBP1-related disorders present with:  

• Seizures  
• Developmental delay  

SIGNS AND SYMPTOMS

Seizures are part of STXBP1-related disorders. Most children will have more than one seizure type.  

The types of seizures may include the following: 

Developmental delay is present in all children with STXBP1-related disorders. Affected children have intellectual disability. This can range from moderate to profound. Many children with STXBP1-related disorders will also be diagnosed with autism spectrum disorder.  

Children with STXBP1-related disorders may also have:

• Hypotonia. Muscle tone is low. Muscles are floppy. 
• Spasticity. There is increased muscle tone. Muscles are tight.  

 Movement disorders may be present in some children with variations in the STXBP1 gene. Atypical movements may be present shortly after birth or they may develop as children age. These movements may resemble Parkinson’s disease.  

CAUSES

STXBP1-related disorders are caused by a variation in the STXBP1 gene. This gene codes for a particular protein that is expressed throughout the brain. This protein is necessary for the release of signals from brain cells. 

Two normal copies of the STXBP1 gene are needed for normal function. Even if only one of the two copies of the gene is different, children will have symptoms.

LABORATORY INVESTIGATIONS

STXBP1-related disorders can be diagnosed with the following:  

• Genetic testing. Genetic testing will show a mutation in STXBP1.  
• Electroencephalogram (EEG). An EEG is a test that measures the electrical activity of the brain. Electrodes are placed on the scalp. The EEG will be abnormal to varying degrees in all affected individuals.  
• MRI. MRI may reveal structural differences in some affected individuals. 

TREATMENT AND THERAPIES

Most children are treated with antiseizure medications. The choice of medication depends on the specific disorder. Many individuals will have to take more than one medication. Many will have seizures that do not respond to treatment.  

These types of therapy can help manage symptoms: 

• Physical therapy 
• Occupational therapy 
• Speech therapy 

A psychologist may be useful in managing behavioral symptoms.  

Genetic counseling can help families better understand the disorder.   

OUTLOOK

Most children will be dependent on caregivers for the rest of their lives. Most will continue to have uncontrolled epilepsy. They may or may not achieve the ability to walk. Most will not achieve the ability to speak. As children age, they may develop movement disorders or a tremor.  

Most adults have:  

• Intellectual disability 
• Behavioral problems  

RELATED DISORDERS

The following disorders may be caused by a mutation in STXBP1: 

• West syndrome 
• Lennox-Gastaut syndrome 
• Ohtahara syndrome 
• Dravet syndrome (not SCN1A-related type) 
• Rett syndrome (phenotype) 
• Early myoclonic epileptic encephalopathy 

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