Dentatorubral-pallidoluysian atrophy

What causes dentatorubral-pallidoluysian atrophy (DRPLA)?

DRPLA is caused by a mutation in the ATN1 gene. This gene provides instructions for making a protein called atrophin 1. Atrophin 1 is suspected to play an important role in nerve cells (neurons) in the brain.

The ATN1 mutation that causes 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 (C), adenine (A), and guanine (G). This segment normally repeats between 6 and 35 times in a row on the gene. In people with DRPLA, the CAG segment is repeated at least 48 times (and sometimes much more). When the CAG trinucleotide repeat is abnormally long, it changes the structure of the atrophin 1 protein. This leads to accumulation of the protein in neurons, which interfere with normal cell functions and cause cell death. This process likely causes the signs and symptoms associated with DRPLA.

Last updated on 05-01-20

How is dentatorubral-pallidoluysian atrophy (DRPLA) inherited?

DRPLA is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

The CAG trinucleotide repeat in the ATN1 gene often increases in size (resulting in a greater number of repeats) when the mutated gene is passed from a parent to a child. This "instability" during transmission of the gene results in a phenomenon called anticipation. This means that larger repeat expansions in later generations are usually associated with an earlier onset of the condition and more severe signs and symptoms. Anticipation seen in DRPLA 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). Affected offspring typically have symptoms 26 to 29 years earlier than affected fathers and 14 to 15 years earlier than affected mothers.

Last updated on 05-01-20

What is the long-term outlook for dentatorubral-pallidoluysian atrophy (DRPLA)?

The symptoms of DRPLA usually worsen quickly. Recurrent seizures and difficulty swallowing (dysphagia) can lead to life-threatening complications, such as pneumonia. On average, people with DRPLA pass away within 13 years of symptom onset. However, some people live to 60 years of age or more.

A 2010 study found that prognosis is associated with the CAG repeat length. People with 65 CAG trinucleotide repeats or more had more severe symptoms, including use of a wheelchair at a younger age and a worse overall prognosis.

Last updated on 05-01-20

How might dentatorubral-pallidoluysian atrophy (DRPLA) be treated?

There is no cure for DRPLA; however there may be ways in which the signs and symptoms can be managed including:

  • Treatment of seizures with anti-epileptic drugs
  • Treatment of psychiatric problems with appropriate psychotropic medications
  • Adaptation of environment and care to the level of dementia
  • Adaptation of educational programs for affected children

A medication typically used to slow the progress of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) called riluzole may also be useful in managing ataxia in people with DRPLA.

Last updated on 05-01-20

Where To Start


Stanford University's HOPES Web site offers a detailed description of DRPLA with illustrations. Click on HOPES to view the information page.

Last updated on 04-27-20

Name: National Ataxia Foundation 600 Highway 169 South Suite 1725
Minneapolis, MN, 55426, United States
Phone: +1-763-553-0020 Fax : +1-763-553-0167 Email: Url:
Name: euro-ATAXIA (European Federation of Hereditary Ataxias) Url:
Name: Ataxia UK 12 Broadbent Close
London, N6 5JW, United Kingdom
Phone: 020 7582 1444 Toll Free: 0845 644 0606 (Helpline) Email: Url:
Name: Epilepsy Foundation 8301 Professional Place East Suite 230
Landover, MD, 20785, United States
Phone: +1-301-459-3700 Toll Free: 800-332-1000 (24/7 Helpline) Fax : +1-301-577-2684 Email: Url: en Español 1-866-748-8008
RETIRED use 2392. Dentatorubral-pallidoluysian atrophy Genetics Home Reference. November, 2008; Reference Link

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