The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.
|Signs and Symptoms||Approximate number of patients (when available)|
|Atrophy of the dentate nucleus||90%|
|Fetal cystic hygroma||90%|
|Abnormal pyramidal signs||5/25|
|Autosomal dominant inheritance||-|
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 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.
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.
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. 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). Affected offspring typically have symptoms 26 to 29 years earlier than affected fathers and 14 to 15 years earlier than affected mothers.
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.
Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.
Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
Gordon Research Conferences CAG Triplet Repeat Disorders and the associated Graduate Research Seminar
Saturday, June 22, 2013 -
Friday, June 28, 2013
Location: Waterville Valley Resort, Waterville Valley, NH
Description: The 2013 Gordon Research Conference on CAG Triplet Repeat Disorders will bring together top scientists from around the world to discuss high-impact, interdisciplinary research on CAG Triplet Repeat Disorders. The objective of the conference is to promote scientific discussion and facilitate interdisciplinary exchange by bringing leading researchers in the field together with a broad range of experts representing; clinicians, diagnosticians, neurobiologists, pathologists, geneticists and molecular biologists.
Contact: Miles Fabian(301) email@example.com
Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
2009 Triplet Repeat Disorders Gordon Conference
Sunday, May 31, 2009 -
Friday, June 5, 2009
Location: Waterville Valley, NH
Description: The top two priorities of this conference were training and the communication of cutting-edge science in the area of CAG triplet repeat disorders. The focus of this conference was on areas of rapid advancement and latest developments. Speakers were selected for their expertise, recent contributions to the field, and ability to provide lively presentations. The structured discussion leaders were instructed to focus on issues that cut across each presentation in a session.
Contact: Dr. Margaret Sutherland, NINDS 301-496-5680
Co-funding Institute(s): National Institute of Neurological Disorders and Stroke
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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. See answer