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Rapid-onset dystonia parkinsonism

Reviewed July 2009

What is rapid-onset dystonia parkinsonism?

Rapid-onset dystonia parkinsonism is a rare movement disorder. "Rapid-onset" refers to the abrupt appearance of signs and symptoms over a period of hours to days. Dystonia is a condition characterized by involuntary, sustained muscle contractions. Parkinsonism can include tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls.

Rapid-onset dystonia parkinsonism causes movement abnormalities that can make it difficult to walk, talk, and carry out other activities of daily life. In this disorder, dystonia affects the arms and legs, causing muscle cramping and spasms. Facial muscles are often affected, resulting in problems with speech and swallowing. The movement abnormalities associated with rapid-onset dystonia parkinsonism tend to begin near the top of the body and move downward, first affecting the facial muscles, then the arms, and finally the legs.

The signs and symptoms of rapid-onset dystonia parkinsonism most commonly appear in adolescence or young adulthood. In some affected individuals, signs and symptoms can be triggered by an infection, physical stress (such as prolonged exercise), emotional stress, or alcohol consumption. The signs and symptoms tend to stabilize within about a month, but they typically do not improve much after that. In some people with this condition, the movement abnormalities abruptly worsen during a second episode several years later.

Some people with rapid-onset dystonia parkinsonism have been diagnosed with anxiety, social phobias, depression, and seizures. It is unclear whether these disorders are related to the genetic changes that cause rapid-onset dystonia parkinsonism.

How common is rapid-onset dystonia parkinsonism?

Rapid-onset dystonia parkinsonism appears to be a rare disorder, although its prevalence is unknown. It has been diagnosed in individuals and families from the United States, Europe, and Korea.

What genes are related to rapid-onset dystonia parkinsonism?

Rapid-onset dystonia parkinsonism is caused by mutations in the ATP1A3 gene. This gene provides instructions for making one part of a larger protein called Na+/K+ ATPase, also known as the sodium pump. This protein is critical for the normal function of nerve cells (neurons) in the brain. It transports charged atoms (ions) into and out of neurons, which is an essential part of the signaling process that controls muscle movement.

Mutations in the ATP1A3 gene reduce the activity of the Na+/K+ ATPase or make the protein unstable. Studies suggest that the defective protein is unable to transport ions normally, which disrupts the electrical activity of neurons in the brain. However, it is unclear how a malfunctioning Na+/K+ ATPase causes the movement abnormalities characteristic of rapid-onset dystonia parkinsonism.

In some people with rapid-onset dystonia parkinsonism, no mutation in the ATP1A3 gene has been identified. The genetic cause of the disorder is unknown in these individuals. Researchers believe that mutations in at least one other gene, which has not been identified, can cause this disorder.

Related Gene(s)

Changes in this gene are associated with rapid-onset dystonia parkinsonism.

  • ATP1A3

How do people inherit rapid-onset dystonia parkinsonism?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered ATP1A3 gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits a mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Not everyone who has an ATP1A3 mutation will ultimately develop the signs and symptoms of rapid-onset dystonia parkinsonism. It is unclear why some people with a gene mutation develop movement abnormalities and others do not.

Where can I find information about diagnosis or management of rapid-onset dystonia parkinsonism?

These resources address the diagnosis or management of rapid-onset dystonia parkinsonism and may include treatment providers.

  • Gene Review: Rapid-Onset Dystonia-Parkinsonism (http://www.ncbi.nlm.nih.gov/books/NBK1115/)
  • Genetic Testing Registry: Dystonia 12 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868681)

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

You may find the following resources about rapid-onset dystonia parkinsonism 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 rapid-onset dystonia parkinsonism?

  • DYT12
  • RDP
  • RODP

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 rapid-onset dystonia parkinsonism?

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

What glossary definitions help with understanding rapid-onset dystonia parkinsonism?

anxiety ; autosomal ; autosomal dominant ; bradykinesia ; caudal ; cell ; depression ; dystonia ; gene ; infection ; involuntary ; ions ; mutation ; Na ; parkinsonism ; prevalence ; protein ; sodium ; stress

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

References

  • Brashear A, Butler IJ, Ozelius LJ, Kramer PI, Farlow MR, Breakefield XO, Dobyns WB. Rapid-onset dystonia-parkinsonism: a report of clinical, biochemical, and genetic studies in two families. Adv Neurol. 1998;78:335-9. (http://www.ncbi.nlm.nih.gov/pubmed/9750930?dopt=Abstract)
  • Brashear A, DeLeon D, Bressman SB, Thyagarajan D, Farlow MR, Dobyns WB. Rapid-onset dystonia-parkinsonism in a second family. Neurology. 1997 Apr;48(4):1066-9. (http://www.ncbi.nlm.nih.gov/pubmed/9109901?dopt=Abstract)
  • Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Münchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Ozelius LJ. The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. Brain. 2007 Mar;130(Pt 3):828-35. Epub 2007 Feb 4. (http://www.ncbi.nlm.nih.gov/pubmed/17282997?dopt=Abstract)
  • Brashear A, Farlow MR, Butler IJ, Kasarskis EJ, Dobyns WB. Variable phenotype of rapid-onset dystonia-parkinsonism. Mov Disord. 1996 Mar;11(2):151-6. (http://www.ncbi.nlm.nih.gov/pubmed/8684384?dopt=Abstract)
  • de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ. Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron. 2004 Jul 22;43(2):169-75. (http://www.ncbi.nlm.nih.gov/pubmed/15260953?dopt=Abstract)
  • Dobyns WB, Ozelius LJ, Kramer PL, Brashear A, Farlow MR, Perry TR, Walsh LE, Kasarskis EJ, Butler IJ, Breakefield XO. Rapid-onset dystonia-parkinsonism. Neurology. 1993 Dec;43(12):2596-602. (http://www.ncbi.nlm.nih.gov/pubmed/8255463?dopt=Abstract)
  • Gene Review: Rapid-Onset Dystonia-Parkinsonism (http://www.ncbi.nlm.nih.gov/books/NBK1115/)
  • Kabakci K, Isbruch K, Schilling K, Hedrich K, de Carvalho Aguiar P, Ozelius LJ, Kramer PL, Schwarz MH, Klein C. Genetic heterogeneity in rapid onset dystonia-parkinsonism: description of a new family. J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):860-2. (http://www.ncbi.nlm.nih.gov/pubmed/15897512?dopt=Abstract)
  • Kramer PL, Mineta M, Klein C, Schilling K, de Leon D, Farlow MR, Breakefield XO, Bressman SB, Dobyns WB, Ozelius LJ, Brashear A. Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13. Ann Neurol. 1999 Aug;46(2):176-82. (http://www.ncbi.nlm.nih.gov/pubmed/10443882?dopt=Abstract)
  • Pittock SJ, Joyce C, O'Keane V, Hugle B, Hardiman MO, Brett F, Green AJ, Barton DE, King MD, Webb DW. Rapid-onset dystonia-parkinsonism: a clinical and genetic analysis of a new kindred. Neurology. 2000 Oct 10;55(7):991-5. (http://www.ncbi.nlm.nih.gov/pubmed/11061257?dopt=Abstract)
  • Zaremba J, Mierzewska H, Lysiak Z, Kramer P, Ozelius LJ, Brashear A. Rapid-onset dystonia-parkinsonism: a fourth family consistent with linkage to chromosome 19q13. Mov Disord. 2004 Dec;19(12):1506-10. (http://www.ncbi.nlm.nih.gov/pubmed/15390049?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: July 2009
Published: July 7, 2014