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Genetics Home Reference: your guide to understanding genetic conditions
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Dystonia 6

Reviewed November 2013

What is dystonia 6?

Dystonia 6 is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. Dystonia 6 can appear at any age from childhood through adulthood; the average age of onset is 18.

The signs and symptoms of dystonia 6 vary among affected individuals. The disorder usually first impacts muscles of the head and neck, causing problems with speaking (dysarthria) and eating (dysphagia). Eyelid twitching (blepharospasm) may also occur. Involvement of one or more limbs is common, and in some cases occurs before the head and neck problems. Dystonia 6 gradually gets worse, and it may eventually involve most of the body.

How common is dystonia 6?

The prevalence of dystonia 6 is unknown. Studies indicate that it likely accounts for between 1 and 3 percent of all cases of dystonia. For reasons that are unclear, the disorder appears to be slightly more prevalent in females than in males.

What genes are related to dystonia 6?

Dystonia 6 is caused by mutations in the THAP1 gene. This gene provides instructions for making a protein that is a transcription factor, which means that it attaches (binds) to specific regions of DNA and regulates the activity of other genes. Through this function, it is thought to help control several processes in the body, including the growth and division (proliferation) of endothelial cells, which line the inside surface of blood vessels and other circulatory system structures called lymphatic vessels. The THAP1 protein also plays a role in the self-destruction of cells that are no longer needed (apoptosis).

Studies indicate that most of the THAP1 gene mutations that cause dystonia 6 affect the stability of the THAP1 protein, reducing the amount of functional THAP1 protein available for DNA binding. Other mutations may impair the protein's ability to bind with the correct regions of DNA. Problems with DNA binding likely disrupt the proper regulation of gene activity, leading to the signs and symptoms of dystonia 6.

A particular THAP1 gene mutation is specific to a Mennonite population in the Midwestern United States in which dystonia 6 was first described. This mutation changes the DNA sequence in a region of the gene known as exon 2. Some researchers use the term DYT6 dystonia to refer to dystonia caused by this particular mutation, and the broader term THAP1 dystonia to refer to dystonia caused by any THAP1 gene mutation. In general, mutations affecting the region of the THAP1 protein that binds to DNA, including the mutation found in the Mennonite population, tend to result in more severe signs and symptoms than mutations affecting other regions of the protein.

Related Gene(s)

Changes in this gene are associated with dystonia 6.

  • THAP1

How do people inherit dystonia 6?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell can be sufficient to cause the disorder. Some people who inherit the altered gene never develop the condition, a situation known as reduced penetrance.

Where can I find information about diagnosis or management of dystonia 6?

These resources address the diagnosis or management of dystonia 6 and may include treatment providers.

  • American Association of Neurological Surgeons (http://www.aans.org/Patient%20Information/Conditions%20and%20Treatments/Dystonia.aspx)
  • Gene Review: Dystonia Overview (http://www.ncbi.nlm.nih.gov/books/NBK1155)
  • Genetic Testing Registry: Dystonia 6, torsion (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1414216)

You might also find information on the diagnosis or management of dystonia 6 in Educational resources (http://www.ghr.nlm.nih.gov/condition/dystonia-6/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/dystonia-6/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about dystonia 6?

You may find the following resources about dystonia 6 helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for dystonia 6?

  • DYT6
  • DYT6 dystonia
  • idiopathic torsion dystonia of mixed type
  • primary dystonia, DYT6 type
  • THAP1 dystonia
  • torsion dystonia 6

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about dystonia 6?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding dystonia 6?

apoptosis ; autosomal ; autosomal dominant ; cell ; DNA ; dysarthria ; dysphagia ; dystonia ; endothelial cells ; exon ; gene ; idiopathic ; inherit ; inherited ; involuntary ; mutation ; penetrance ; population ; prevalence ; proliferation ; protein ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Blanchard A, Ea V, Roubertie A, Martin M, Coquart C, Claustres M, Béroud C, Collod-Béroud G. DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene. Hum Mutat. 2011 Nov;32(11):1213-24. doi: 10.1002/humu.21564. Epub 2011 Sep 15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21793105?dopt=Abstract)
  • Bressman SB, Raymond D, Fuchs T, Heiman GA, Ozelius LJ, Saunders-Pullman R. Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol. 2009 May;8(5):441-6. doi: 10.1016/S1474-4422(09)70081-X. Epub 2009 Apr 1. (http://www.ncbi.nlm.nih.gov/pubmed/19345147?dopt=Abstract)
  • Campagne S, Muller I, Milon A, Gervais V. Towards the classification of DYT6 dystonia mutants in the DNA-binding domain of THAP1. Nucleic Acids Res. 2012 Oct;40(19):9927-40. doi: 10.1093/nar/gks703. Epub 2012 Jul 27. (http://www.ncbi.nlm.nih.gov/pubmed/22844099?dopt=Abstract)
  • Cheng FB, Ozelius LJ, Wan XH, Feng JC, Ma LY, Yang YM, Wang L. THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression. J Neurol. 2012 Feb;259(2):342-7. doi: 10.1007/s00415-011-6196-5. Epub 2011 Jul 29. (http://www.ncbi.nlm.nih.gov/pubmed/21800139?dopt=Abstract)
  • Djarmati A, Schneider SA, Lohmann K, Winkler S, Pawlack H, Hagenah J, Brüggemann N, Zittel S, Fuchs T, Raković A, Schmidt A, Jabusch HC, Wilcox R, Kostić VS, Siebner H, Altenmüller E, Münchau A, Ozelius LJ, Klein C. Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. Lancet Neurol. 2009 May;8(5):447-52. doi: 10.1016/S1474-4422(09)70083-3. Epub 2009 Apr 1. (http://www.ncbi.nlm.nih.gov/pubmed/19345148?dopt=Abstract)
  • Houlden H, Schneider SA, Paudel R, Melchers A, Schwingenschuh P, Edwards M, Hardy J, Bhatia KP. THAP1 mutations (DYT6) are an additional cause of early-onset dystonia. Neurology. 2010 Mar 9;74(10):846-50. doi: 10.1212/WNL.0b013e3181d5276d. (http://www.ncbi.nlm.nih.gov/pubmed/20211909?dopt=Abstract)
  • LeDoux MS, Xiao J, Rudzińska M, Bastian RW, Wszolek ZK, Van Gerpen JA, Puschmann A, Momčilović D, Vemula SR, Zhao Y. Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases. Parkinsonism Relat Disord. 2012 Jun;18(5):414-25. doi: 10.1016/j.parkreldis.2012.02.001. Epub 2012 Feb 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22377579?dopt=Abstract)
  • Xiromerisiou G, Houlden H, Scarmeas N, Stamelou M, Kara E, Hardy J, Lees AJ, Korlipara P, Limousin P, Paudel R, Hadjigeorgiou GM, Bhatia KP. THAP1 mutations and dystonia phenotypes: genotype phenotype correlations. Mov Disord. 2012 Sep 1;27(10):1290-4. doi: 10.1002/mds.25146. Epub 2012 Aug 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22903657?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2013
Published: September 8, 2014