Dentatorubral-pallidoluysian atrophy, commonly known as DRPLA, is a progressive brain disorder that causes involuntary movement disorders, 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). It is described in more detail at https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy#.
Frequency
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.
Cause
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.
Management
https://www.ncbi.nlm.nih.gov/books/NBK1491/
As explained in the above link:
Current management involves treatment of the symptoms including
- Standard antiepileptic drugs (AEDs) for seizures;
- Appropriate psychotropic medications for psychiatric manifestations;
- Symptomatic treatment of ataxia with riluzole and rehabilitation therapy;
- Adaptation of environment and care to the level of dementia;
- Appropriate educational programs for children.
© 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.
GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2019 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web;
Acknowledgment: NIH US National Library of Medicine
Information Sites
NIH – Genetics Home Reference
https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy#
OMIM® – Online Mendelian Inheritance in Man
https://www.omim.org/entry/125370
National Centre for Biotechnology-Gene Review
https://www.ncbi.nlm.nih.gov/books/NBK1491/
GARD – Genetic and Rare Diseases Information Centre
https://rarediseases.info.nih.gov/diseases/5643/dentatorubral-pallidoluysian-atrophy
Learn More About DRPLA
Living with dentatorubral-pallidoluysian atrophy can be challenging. This is why we at CureDRPLA are committed to gaining information on this brain disorder and what can be done to help those who suffer. Contact us today if you have questions or data to share with us.