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ABOUT DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY

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.