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Genetics Home Reference: your guide to understanding genetic conditions
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Dentatorubral-pallidoluysian atrophy

(often shortened to DRPLA)
Reviewed November 2008

What is DRPLA?

Dentatorubral-pallidoluysian atrophy, commonly known as DRPLA, is a progressive brain disorder that causes involuntary movements, mental and emotional problems, and a decline in thinking ability. The average age of onset of DRPLA is 30 years, but this condition can appear anytime from infancy to mid-adulthood.

The signs and symptoms of DRPLA differ somewhat between affected children and adults. When DRPLA appears before age 20, it most often involves episodes of involuntary muscle jerking or twitching (myoclonus), seizures, behavioral changes, intellectual disability, and problems with balance and coordination (ataxia). When DRPLA begins after age 20, the most frequent signs and symptoms are ataxia, uncontrollable movements of the limbs (choreoathetosis), psychiatric symptoms such as delusions, and deterioration of intellectual function (dementia).

How common is DRPLA?

DRPLA is most common in the Japanese population, where it has an estimated incidence of 2 to 7 per million people. This condition has also been seen in families from North America and Europe.

Although DRPLA is rare in the United States, it has been studied in a large African-American family from the Haw River area of North Carolina. When the family was first identified, researchers named the disorder Haw River syndrome. Later, researchers determined that Haw River syndrome and DRPLA are the same condition.

What genes are related to DRPLA?

DRPLA is caused by a mutation in the ATN1 gene. This gene provides instructions for making a protein called atrophin 1. Although the function of atrophin 1 is unclear, it likely plays an important role in nerve cells (neurons) in many areas of the brain.

The ATN1 mutation that underlies DRPLA involves a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, this segment is repeated 6 to 35 times within the ATN1 gene. In people with DRPLA, the CAG segment is repeated at least 48 times, and the repeat region may be two or three times its usual length. The abnormally long CAG trinucleotide repeat changes the structure of atrophin 1. This altered protein accumulates in neurons and interferes with normal cell functions. The dysfunction and eventual death of these neurons lead to uncontrolled movements, intellectual decline, and the other characteristic features of DRPLA.

Related Gene(s)

Changes in this gene are associated with dentatorubral-pallidoluysian atrophy.

  • ATN1

How do people inherit DRPLA?

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. In most cases, an affected person has one parent with the condition.

As the altered ATN1 gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. Larger repeat expansions are usually associated with an earlier onset of the disorder and more severe signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATN1 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).

Where can I find information about diagnosis or management of DRPLA?

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

  • Gene Review: DRPLA (http://www.ncbi.nlm.nih.gov/books/NBK1491)
  • Genetic Testing Registry: Dentatorubral pallidoluysian atrophy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0751781)
  • MedlinePlus Encyclopedia: Dementia (http://www.nlm.nih.gov/medlineplus/ency/article/000739.htm)
  • MedlinePlus Encyclopedia: Epilepsy (http://www.nlm.nih.gov/medlineplus/ency/article/000694.htm)

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

You may find the following resources about DRPLA 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 DRPLA?

  • Haw River syndrome
  • Myoclonic epilepsy with choreoathetosis
  • Naito-Oyanagi disease
  • NOD

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 DRPLA?

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

What glossary definitions help with understanding DRPLA?

adenine ; anticipation ; ataxia ; atrophy ; autosomal ; autosomal dominant ; cell ; cerebellum ; cytosine ; dementia ; disability ; DNA ; epilepsy ; gene ; guanine ; incidence ; inheritance ; inherited ; involuntary ; maternal ; maternal inheritance ; mutation ; myoclonus ; myoclonus epilepsy ; population ; protein ; syndrome ; trinucleotide repeat

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

References

  • Adachi N, Arima K, Asada T, Kato M, Minami N, Goto Yi, Onuma T, Ikeuchi T, Tsuji S, Hayashi M, Fukutani Y. Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):258-60. (http://www.ncbi.nlm.nih.gov/pubmed/11449034?dopt=Abstract)
  • Gene Review: DRPLA (http://www.ncbi.nlm.nih.gov/books/NBK1491)
  • Hayashi Y, Kakita A, Yamada M, Koide R, Igarashi S, Takano H, Ikeuchi T, Wakabayashi K, Egawa S, Tsuji S, Takahashi H. Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain. Acta Neuropathol. 1998 Dec;96(6):547-52. (http://www.ncbi.nlm.nih.gov/pubmed/9845282?dopt=Abstract)
  • Ikeuchi T, Koide R, Onodera O, Tanaka H, Oyake M, Takano H, Tsuji S. Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA. Clin Neurosci. 1995;3(1):23-7. (http://www.ncbi.nlm.nih.gov/pubmed/7614090?dopt=Abstract)
  • Ikeuchi T, Onodera O, Oyake M, Koide R, Tanaka H, Tsuji S. Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Semin Cell Biol. 1995 Feb;6(1):37-44. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7620120?dopt=Abstract)
  • Katsuno M, Banno H, Suzuki K, Takeuchi Y, Kawashima M, Tanaka F, Adachi H, Sobue G. Molecular genetics and biomarkers of polyglutamine diseases. Curr Mol Med. 2008 May;8(3):221-34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18473821?dopt=Abstract)
  • Koide R, Onodera O, Ikeuchi T, Kondo R, Tanaka H, Tokiguchi S, Tomoda A, Miike T, Isa F, Beppu H, Shimizu N, Watanabe Y, Horikawa Y, Shimohata T, Hirota K, Ishikawa A, Tsuji S. Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings. Neurology. 1997 Dec;49(6):1605-12. (http://www.ncbi.nlm.nih.gov/pubmed/9409354?dopt=Abstract)
  • Licht DJ, Lynch DR. Juvenile dentatorubral-pallidoluysian atrophy: new clinical features. Pediatr Neurol. 2002 Jan;26(1):51-4. (http://www.ncbi.nlm.nih.gov/pubmed/11814736?dopt=Abstract)
  • Tsuji S. Dentatorubral-pallidoluysian atrophy: clinical aspects and molecular genetics. Adv Neurol. 2002;89:231-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11968450?dopt=Abstract)
  • Yamada M, Wood JD, Shimohata T, Hayashi S, Tsuji S, Ross CA, Takahashi H. Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral-pallidoluysian atrophy. Ann Neurol. 2001 Jan;49(1):14-23. (http://www.ncbi.nlm.nih.gov/pubmed/11198291?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 2008
Published: November 17, 2014