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Genetic and Rare Diseases Information Center (GARD)

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Dentatorubral-pallidoluysian atrophy

Other Names for this Disease
  • Ataxia, chorea, seizures, and dementia
  • Dentatorubropallidoluysian atrophy
  • Haw River syndrome
  • Myoclonic epilepsy with choreoathetosis
More Names
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Your Question

Is DRPLA treatable? Also, will it eventually kill someone? I just found out my nephew has it and I want to understand as much as possible about it.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is dentatorubral-pallidoluysian atrophy?

Dentatorubral-pallidoluysian atrophy (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 the condition can appear anytime from infancy to mid-adulthood. Specific signs and symptoms may differ among affected individuals and sometimes affects children and adults differently. DRPLA is caused by a mutation in the ATN1 gene and is inherited in an autosomal dominant manner.[1] Treatment is symptomatic and supportive.[2]
Last updated: 9/5/2012

What are the signs and symptoms of dentatorubral-pallidoluysian atrophy (DRPLA)?

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).[1] Epileptic seizures occur in all individuals with onset before 20 years of age.[3]

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).[1] Seizures are less frequent in individuals with onset between the ages of 20 and 40. Seizures are rare in individuals with onset after age 40.[3]

Individuals who have inherited the condition from an affected parent typically have symptoms 26 to 29 years earlier than affected fathers, and 14 to 15 years earlier than affected mothers.[3]
Last updated: 9/5/2012

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. Although the function of atrophin 1 is unclear, it likely plays an important role in nerve cells (neurons) in many areas of the brain.[1]

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, adenine, and guanine) that appear multiple times in a row on the gene. Normally, this CAG 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 sometimes much more). The abnormally long CAG trinucleotide repeat changes the structure of the atrophin 1 protein, which then accumulates in neurons and interferes with normal cell functions. The dysfunction and eventual death of these neurons lead to the signs and symptoms associated with DRPLA.[1]

Last updated: 9/5/2012

How is dentatorubral-pallidoluysian atrophy (DRPLA) inherited?

DRPLA is inherited in an autosomal dominant pattern, which means that one copy of the mutated gene in each cell is sufficient to cause the disorder. The condition may be inherited from an affected parent or may occur for the first time in the affected individual. In most cases, an affected person has one parent with the condition.[1]

The CAG trinucleotide repeat in the ATN1 gene often increases in size (resulting in a greater number of repeats) when the mutated gene is transmitted from a parent to a child. This "instability" during transmission of the gene results in a phenomenon called anticipation.[3] This means that larger repeat expansions in subsequent 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).[1] Affected offspring typically have symptoms 26 to 29 years earlier than affected fathers and 14 to 15 years earlier than affected mothers.[3]

Last updated: 9/5/2012

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

There is no cure for DRPLA; treatment is generally symptomatic and supportive.[2] Management of signs and symptoms may include:[3] 

  • 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.
Last updated: 9/5/2012

What is the prognosis for individuals with dentatorubral-pallidoluysian atrophy (DRPLA)?

DRPLA is associated with a poor prognosis. The condition progresses rather rapidly, with the average duration being about 13 years. Recurrent seizures and difficulty swallowing (dysphagia), with frequent fluid and food aspiration, lead to pneumonia and subsequent death. However, some affected individuals reach 60 years of age or more.[4]

In a study published in 2010, the authors noted that individuals with DRPLA became wheelchair-bound at a median age of 33 years (with a range of 3-77 years) and died at a median age of 49 years (with a range of 18-80 years). The ages that the individuals in the study became wheelchair-bound, and the age at death, strongly correlated with the expanded CAG repeat length. The patients with 65 CAG trinucleotide repeats or more showed a more severe long-term disability and a poorer prognosis.[5]

To read more on our Web site about DRPLA and CAG trinucleotide repeat mutations, click here.
Last updated: 9/5/2012