STXBP1 encephalopathy with epilepsy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. The signs and symptoms of this condition typically begin in infancy but can first appear later in childhood or early adulthood. In many affected individuals, seizures stop in early childhood with the other neurological problems continuing throughout life. However, some people with STXBP1 encephalopathy with epilepsy have seizures that persist.
The most common seizures in STXBP1 encephalopathy with epilepsy are infantile spasms, which occur before age 1 and consist of involuntary muscle contractions. Other seizure types that can occur in infants with this condition include involuntary muscle twitches (myoclonic seizures), sudden episodes of weak muscle tone (atonic seizures), partial or complete loss of consciousness (absence seizures), or loss of consciousness with muscle rigidity and convulsions (tonic-clonic seizures). Most people with STXBP1 encephalopathy with epilepsy have more than one type of seizure. In about one-quarter of individuals, the seizures are described as refractory because they do not respond to therapy with anti-epileptic medications.
Other signs and symptoms of STXBP1 encephalopathy with epilepsy include intellectual disability that is often moderate to profound. Affected individuals also have delayed development of speech and walking; in some, these skills never fully develop. Movement and behavior disorders may also occur. Many affected individuals have feeding difficulties. In some cases, areas of brain tissue loss (atrophy) have been found on medical imaging.
The prevalence of STXBP1 encephalopathy with epilepsy is unknown. At least 200 individuals with this condition have been described in the medical literature.
As its name indicates, STXBP1 encephalopathy with epilepsy is caused by mutations in the STXBP1 gene. This gene provides instructions for making syntaxin-binding protein 1. In nerve cells (neurons), this protein helps regulate the release of chemical messengers called neurotransmitters from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.
STXBP1 gene mutations reduce the amount of functional protein produced from the gene, which impairs the release of neurotransmitters from neurons. A change in neurotransmitter levels can lead to uncontrolled activation (excitation) of neurons, which causes seizures. This altered neuronal activity does not appear to impair the development or survival of neurons; the cause of the encephalopathy and other neurological problems in this condition is unclear.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Most cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.
- early-infantile epileptic encephalopathy 4
- STXBP1 epileptic encephalopathy
- STXBP1-related early-onset encephalopathy
- STXBP1-related epileptic encephalopathy
- Boston Children's Hospital: Epilepsy and Seizure Disorder in Children
- Centers for Disease Control and Prevention: Epilepsy
- Centers for Disease Control and Prevention: Facts About Developmental Disabilities
- MalaCards: epileptic encephalopathy, early infantile, 4
- MalaCards: stxbp1 encephalopathy with epilepsy
- Merck Manual Consumer Version: Seizure Disorders
- Orphanet: Orphanet: Early infantile epileptic encephalopathy
- Unique: Rare Chromosome Disorder Support Group (UK) (PDF)