Rare Ophthalmology News

Disease Profile

Dentatorubral-pallidoluysian atrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

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ICD-10

G11.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

DRPLA; Myoclonic epilepsy with choreoathetosis; Naito Oyanagi disease;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases;

Summary

Dentatorubral-pallidoluysian atrophy (DRPLA) is a brain disorder that worsens over time. It can lead to involuntary movements, mental and emotional problems, and a decline in thinking ability. Symptoms usually appear around 30 years of age, but can occur anytime from infancy to mid-adulthood. Specific signs and symptoms may differ and include seizures, issues with balance and coordination (ataxia), and involuntary muscle jerking or twitching (myoclonus). Other symptoms that usually appear in adulthood include dementia and psychiatric conditions. DRPLA is caused by a mutation in the ATN1 gene and is inherited in an autosomal dominant manner.[1][2][3] Although there is no specific treatment or cure for DRPLA, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person’s symptoms.[3]

Symptoms

The signs and symptoms of DRPLA may differ depending on whether they begin in childhood or adulthood.[1][3]

When DRPLA begins before 20 years of age, it typically involves:[1][3]

  • Involuntary muscle jerking or twitching (myoclonus)
  • Seizures
  • Behavioral changes
  • Intellectual disability (cognitive issues)
  • Problems with balance and coordination (ataxia)

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

When DRPLA begins after 20 years of age, the most frequent signs and symptoms include:[1][3]

  • Ataxia
  • Uncontrollable movements of the limbs (choreoathetosis)
  • Psychiatric symptoms (such as delusions)
  • Dementia

Seizures are less frequent in people with onset between the ages of 20 and 40 and rarely occur in those with onset after age 40.[3]

People 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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Atrophy of the dentate nucleus
0007047
Fetal cystic hygroma
0010878
Progressive cerebellar ataxia
0002073
30%-79% of people have these symptoms
Action tremor
0002345
Choreoathetosis
0001266
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Dysarthria
Difficulty articulating speech
0001260
Dysdiadochokinesis
Difficulty performing quick and alternating movements
0002075
Dysmetria
Lack of coordination of movement
0001310
Dyssynergia
0010867
Gait ataxia
Inability to coordinate movements when walking
0002066
Hyperintensity of cerebral white matter on MRI
0030890
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Impaired proprioception
0010831
Limb ataxia
0002070
Myoclonus
0001336
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Ophthalmoparesis
Weakness of muscles controlling eye movement
0000597
Optic neuropathy
Damaged optic nerve
0001138
Saccadic smooth pursuit
0001152
Seizure
0001250
Truncal ataxia
Instability or lack of coordination of central trunk muscles
0002078
5%-29% of people have these symptoms
Blepharospasm
Eyelid spasm
Eyelid twitching
Involuntary closure of eyelid
Spontaneous closure of eyelid

[ more ]

0000643
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Oromandibular dystonia
0012048
1%-4% of people have these symptoms
Abnormal pyramidal sign
0007256
Ataxia
0001251
Chorea
0002072
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Genetic anticipation
0003743

Cause

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.[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 (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.[1]

Diagnosis

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.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no cure for DRPLA; however there may be ways in which the signs and symptoms can be managed including:[2][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

    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.[3][4]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Organizations Providing General Support

          Learn more

          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.

          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.
          • Genetics Home Reference (GHR) contains information on Dentatorubral-pallidoluysian atrophy. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Dentatorubral-pallidoluysian atrophy. Click on the link to view a sample search on this topic.

              References

              1. Dentatorubral-pallidoluysian atrophy. Genetics Home Reference (GHR). November 2008; https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy.
              2. Fujioka S, Whaley N, Wszolek Z. Dentatorubral pallidoluysian atrophy. Orphanet. May 2011; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101.
              3. Veneziano L, Frontali M. DRPLA. GeneReviews. June 9, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1491/.
              4. van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM et al. EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood.. Eur J Neurol. April 21, 2014; 552-62. https://www.ncbi.nlm.nih.gov/pubmed/24418350.
              5. Hasegawa A. Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy: a correlation with CAG repeat length. Mov Disord. August 15, 2010; 25(11):1694-1700. https://www.ncbi.nlm.nih.gov/pubmed/20589872.

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