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Disease Profile

Rapid-onset dystonia-parkinsonism

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 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

G24.1

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)

DYT12; RDP; DYT-ATP1A3;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 71517

Definition
Rapid-onset dystonia-parkinsonism (RDP) is a very rare movement disorder, characterized by the abrupt onset of parkinsonism and dystonia, often triggered by physical or psychological stress.

Epidemiology
The prevalence is unknown. Fewer than 100 patients have been described worldwide to date.

Clinical description
RDP typically presents in childhood or early adulthood (but age of onset can range from 4-55 years) with the abrupt onset of dystonia along with parkinsonism (bradykinesia and postural instability) with a rostrocaudal gradient and prominent bulbar symptoms (dysarthria and dysphagia) that do not respond to dopaminergic medication. Symptoms may develop over several minutes to 30 days, after which time they stabilize. Often onset is triggered by physical exertion, fever, extreme heat, childbirth, excessive alcohol consumption or emotional stress. Some patients experience mild upper limb dystonia (mainly in the hands) and cramping before disease onset occurs. In most cases the disease stabilizes, but a few cases have been reported where a second episode of worsening of symptoms occurred 1-9 years after initial onset. In rare cases seizures, anxiety and depression have been reported. Recently, a variant phenotype in infants (<4 years of age) has been reported with initially episodic hypotonia, gait ataxia, motor delay, and speech and swallowing difficulties.

Etiology
RDP is caused by several missense mutations in the ATP1A3 gene (19q13.2) encoding the sodium/potassium-transporting ATPase subunit alpha-3 protein, which is important for maintaining the electrochemical gradients of potassium and sodium across the plasma membrane. These mutations are thought to lead to neuronal dysfunction. Other genes, which have not yet been identified, may also be involved.

Diagnostic methods
Diagnosis is based on the sudden onset of clinical manifestations (parkinsonism and dystonia), the finding of low homovanillic acid concentrations in cerebrospinal fluid (CSF), normal brain imaging studies and the lack of response to levodopa (L-dopa) therapy. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies show normal dopamine reuptake in dopamine transporters. A mutation in the ATP1A3 gene may confirm diagnosis.

Differential diagnosis
Differential diagnosis includes other forms of dystonia-parkinsonism, such as young adult-onset parkinsonism, dopa-responive dystonia (DRD), dystonia 16 (DYT16) and X-linked dystonia parkinsonism (DYT3). Unlike DYT3 and other forms of young-onset parkinsonism, RDP is not a neurodegenerative disorder.

Antenatal diagnosis
Prenatal diagnosis is possible in families where a disease causing mutation is known.

Genetic counseling
RDP is inherited in an autosomal dominant manner with reduced penetrance, and genetic counseling is possible and recommended. De novo mutations are also observed.

Management and treatment
There is no effective treatment for RDP at present. L-dopa is ineffective. Pallidal deep brain stimulation (DBS) has shown limited or no therapeutic effects. If present, seizures, anxiety and depression can be treated with standard therapy. High-dose benzodiazepines and possibly other muscle relaxants may offer some symptomatic relief. All known triggers of RDP should be avoided. Physical therapy is recommended.

Prognosis
There is no effect on life expectancy, but quality of life is severely affected.

Visit the Orphanet disease page for more resources.

Symptoms

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
30%-79% of people have these symptoms
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Drooling
Dribbling
0002307
Dysarthria
Difficulty articulating speech
0001260
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Gait ataxia
Inability to coordinate movements when walking
0002066
Hypomimic face
Dull facial expression
0000338
Limb dystonia
0002451
Motor delay
0001270
Mutism
Inability to speak
Muteness

[ more ]

0002300
Parkinsonism
0001300
Postural instability
Balance impairment
0002172
Torticollis
Wry neck
0000473
Young adult onset
0011462
5%-29% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Cerebellar atrophy
Degeneration of cerebellum
0001272
Depressivity
Depression
0000716
Emotional lability
Emotional instability
0000712
Resting tremor
Tremor at rest
0002322
Seizure
0001250
1%-4% of people have these symptoms
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Fever
0001945
Incomplete penetrance
0003829
Unsteady gait
Unsteady walk
0002317

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.

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.

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.
  • 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 Rapid-onset dystonia-parkinsonism. Click on the link to view a sample search on this topic.