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Disease Profile

Myoclonus-dystonia

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

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)

DYT11; Dystonia, alcohol responsive; Hereditary essential myoclonus;

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.
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Orpha Number: 36899

Definition
Myoclonusdystonia syndrome (MDS) is a rare movement disorder characterized by mild to moderate dystonia along with 'lightning-like' myoclonic jerks.

Epidemiology
The estimated prevalence of MDS in Europe is 1/500,000.

Clinical description
Disease onset usually occurs in the first or second decade of life. Myoclonus is usually the presenting manifestation and is described as swift ''lightning-like'' jerks that can rarely appear at rest but that are usually triggered by complex motor tasks such as drawing and writing. These movements mainly affect the neck, arms and trunk but can also rarely be seen in the legs or the larynx. In two thirds of cases, dystonia is also experienced in the form of focal or cervical dystonia (see these terms), which may be only mild and does not exacerbate with time. Postural and other forms of tremor have sometimes been reported. MDS is often associated with depression, anxiety, panic attacks, obsessive-compulsive behavior and personality disorders and alcohol abuse. Isolated torticollis is seen in extremely rare cases.

Etiology
The only known causative gene of MDS is the epsilon-sarcoglycan (SGCE) gene (7q21.3), encoding a transmembrane protein that is part of the dystrophin-associated glycoprotein complex found in skeletal and cardiac muscle. The epsilon-sarcoglycan protein is also abundant in monoaminergic neurons, cerebellar Purkinje cells, the cortex and the hippocampus of the brain. In one family with MDS, linkage to chromosome 18p has been reported (named DYT15), but the gene has not yet been identified.

Diagnostic methods
Diagnosis is based on the presence of characteristic clinical symptoms. Neuroimaging studies are normal. Genetic molecular testing of SGCE can confirm the diagnosis.

Differential diagnosis
Differential diagnosis includes cervical dystonia, Dopa-responsive dystonia, Tourette syndrome, familial cortical myoclonus, Wilson disease, spinocerebellar ataxia type 3 (SCA3) and type 14 (SCA14), ataxia with vitamin E deficiency, genetic disorders with myoclonus as a major component (e.g. Unverricht-Lundborg disease, Lafora disease) (see these terms) and other secondary forms of dystonia.

Antenatal diagnosis
Prenatal testing is possible in families where a disease-causing mutation is identified.

Genetic counseling
MDS is inherited in an autosomal dominant manner. However, the SGCE gene is maternally imprinted, therefore in most cases (95%) a patient who inherits the mutation from their mother will remain healthy and only those that inherit the mutation from their father will develop MDS. De novo mutations also occur. Genetic counseling is recommended in those with a known mutation.

Management and treatment
Treatment plans are individualized to a patient's presenting symptoms. Benzodiazepines (clonazepam) and antiepileptic drugs (valproate, levetiracetam) are effective in relieving myoclonus and tremor, but patients should be carefully monitored. Similarly, alcohol frequently improves symptoms temporarily, but its long term use is not recommended. Injections of botulinum toxin can relieve focal and cervical dystonia. If these treatments fail or are insufficient, bilateral deep brain stimulation (DBS) of the internal globus pallidum (Gpi) and the central intermediate nucleus (VIM) of the thalamus have shown positive results in providing lasting relief from both myoclonus and dystonia. Gpi stimulation is often sufficient in treating MDS, and may be favored over VIM stimulation, which generally has very little effect on dystonia. In a staged surgical procedure, quadruple stimulation (VIM and Gpi) may also be considered in selected cases.

Prognosis
Patients with MDS have normal life-expectancy, but quality of life can be 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
80%-99% of people have these symptoms
Limb myoclonus
0045084
Spinal myoclonus
0010531
30%-79% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Depressivity
Depression
0000716
Obsessive-compulsive behavior
Obsessive compulsive behavior
0000722
Panic attack
0025269
Personality disorder
0012075
Torticollis
Wry neck
0000473
Writer's cramp
0002356
5%-29% 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
Agoraphobia
Fear of open spaces
0000756
Autosomal dominant inheritance
0000006
Incomplete penetrance
0003829
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Myoclonus
0001336
Tremor
0001337

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.

    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

      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

        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 Myoclonus-dystonia. Click on the link to view a sample search on this topic.