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STXBP1 encephalopathy with epilepsy

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Description

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.

Frequency

The prevalence of STXBP1 encephalopathy with epilepsy is unknown. At least 200 individuals with this condition have been described in the medical literature.

Causes

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.

Inheritance

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.

Other Names for This Condition

  • early-infantile epileptic encephalopathy 4
  • EIEE4
  • STXBP1 epileptic encephalopathy
  • STXBP1-related early-onset encephalopathy
  • STXBP1-related epileptic encephalopathy

Additional Information & Resources

Genetic and Rare Diseases Information Center

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Barcia G, Chemaly N, Gobin S, Milh M, Van Bogaert P, Barnerias C, Kaminska A, Dulac O, Desguerre I, Cormier V, Boddaert N, Nabbout R. Early epileptic encephalopathies associated with STXBP1 mutations: Could we better delineate the phenotype? Eur J Med Genet. 2014 Jan;57(1):15-20. doi: 10.1016/j.ejmg.2013.10.006. Epub 2013 Nov 1. Citation on PubMed
  • Di Meglio C, Lesca G, Villeneuve N, Lacoste C, Abidi A, Cacciagli P, Altuzarra C, Roubertie A, Afenjar A, Renaldo-Robin F, Isidor B, Gautier A, Husson M, Cances C, Metreau J, Laroche C, Chouchane M, Ville D, Marignier S, Rougeot C, Lebrun M, de Saint Martin A, Perez A, Riquet A, Badens C, Missirian C, Philip N, Chabrol B, Villard L, Milh M. Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases. Epilepsia. 2015 Dec;56(12):1931-40. doi: 10.1111/epi.13214. Epub 2015 Oct 29. Citation on PubMed
  • Gupta A. STXBP1-Related EOEE - Early Onset Epilepsy AND Encephalopathy, or is it Early Onset Epileptic Encephalopathy? Epilepsy Curr. 2016 Sep-Oct;16(5):302-304. Citation on PubMed or Free article on PubMed Central
  • Patzke C, Han Y, Covy J, Yi F, Maxeiner S, Wernig M, Südhof TC. Analysis of conditional heterozygous STXBP1 mutations in human neurons. J Clin Invest. 2015 Sep;125(9):3560-71. doi: 10.1172/JCI78612. Epub 2015 Aug 17. Citation on PubMed or Free article on PubMed Central
  • Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, Benkel-Herrenbrueck I, Benoit V, Budetta M, Caliebe A, Cantalupo G, Capovilla G, Casara G, Courage C, Deprez M, Destrée A, Dilena R, Erasmus CE, Fannemel M, Fjær R, Giordano L, Helbig KL, Heyne HO, Klepper J, Kluger GJ, Lederer D, Lodi M, Maier O, Merkenschlager A, Michelberger N, Minetti C, Muhle H, Phalin J, Ramsey K, Romeo A, Schallner J, Schanze I, Shinawi M, Sleegers K, Sterbova K, Syrbe S, Traverso M, Tzschach A, Uldall P, Van Coster R, Verhelst H, Viri M, Winter S, Wolff M, Zenker M, Zoccante L, De Jonghe P, Helbig I, Striano P, Lemke JR, Møller RS, Weckhuysen S. STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology. 2016 Mar 8;86(10):954-62. doi: 10.1212/WNL.0000000000002457. Epub 2016 Feb 10. Review. Citation on PubMed
  • Yamamoto T, Shimojima K, Yano T, Ueda Y, Takayama R, Ikeda H, Imai K. Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy. Brain Dev. 2016 Mar;38(3):280-4. doi: 10.1016/j.braindev.2015.09.004. Epub 2015 Sep 16. Citation on PubMed
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