Dystrophy, Myotonic

Dystrophy, Myotonic

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Dystrophy, Myotonic is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Curschmann-Batten-Steinert syndrome
  • DM
  • myotonia atrophica
  • Steinert disease
  • dystrophia myotonia

Disorder Subdivisions

  • myotonic dystrophy type 1 (DM1)
  • myotonic dystrophy type 2 (DM2)

General Discussion

Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multi-system disorder that affects both smooth and skeletal muscles and may affect the central nervous system, heart, eyes, and/or endocrine systems. There are three types of DM1 that are distinguished by the severity of disease and age of onset. Mild DM1 is characterized by cataracts and sustained muscle contractions (myotonia). Classic DM1 is characterized by muscle weakness and wasting (atrophy), cataracts, myotonia and abnormalities in the heart's conduction of electrical impulses. Congenital DM1 is characterized by muscle weakness (hypotonia), difficulty breathing, mental retardation and early death.



DM1 is caused by an abnormality in the DMPK gene. Affected individuals have an increased number of copies of a portion of this gene called CTG. The greater the number of repeated copies of CTG, the more severe the disorder.



Myotonic dystrophy type 2 (DM2), formerly called proximal myotonic myopathy (PROMM) is an autosomal dominant disorder with symptoms that are similar to DM1, but tend to be milder and more variable than DM1. DM2 is an autosomal dominant genetic disorder caused by an abnormality in the ZNF9 gene on chromosome 3q. Affected individuals have an increased number of copies of a portion of this gene.

Symptoms

Individuals with mild DM1 have cataracts, mild myotonia and diabetes mellitus. Life span is usually in the normal range.



Individuals with classic DM1 have muscle weakness and atrophy, myotonia, cataracts and frequently have cardiac conduction abnormalities. Symptoms usually begin between the ages of 20 and 40, but disease onset can sometimes occur in childhood or after age 40. Distal muscle weakness leading to a gait disturbance and facial muscle weakness are often the first symptoms. Physical disability that requires a wheelchair eventually occurs in approximately 50% of affected individuals. Average lifespan is in the range of 48-55 years.



Infants with congenital DM1 have overall muscle weakness, facial muscle weakness and breathing difficulties. Death in the newborn period is common. Those who survive develop a progressive myopathy and frequently have mental retardation. Average lifespan for those who survive the newborn period is 45 years.



Symptoms of DM2 are similar to DM1 but tend to be milder and more variable.

Causes

DM1 is caused by an abnormality in the DMPK gene located on chromosome 19 at 19q13.2-q13.3. Affected individuals have an increased number of copies of a portion of this gene called CTG. The number of CTG repeats can increase from one generation to the next. The greater the number of repeated copies of CTG, the more severe the disorder. Congenital DM1 is almost always a result of the child inheriting an abnormal DMPK gene from the mother.



DM2 is caused by an abnormality in the ZNF9 gene on chromosome 3q. Affected individuals have an increased number of copies of a portion of this gene. The number of repeated copies can increase from one generation to the next. The greater the number of repeated copies, the more severe the disorder.



DM1 and DM2 are inherited as autosomal dominant genetic traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome19q13.2" refers to band 13.2 on the long arm of chromosome 19. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Approximately 98% of individuals with myotonic dystrophy have DM1 and 2% have DM2.

The prevalence of DM1 ranges from 1:100,000 in parts of Japan to 1:10,000 in Iceland. In the United States the incidence of DM1 is estimated to be about 1:8,000. More than 400 individuals have been reported with DM2.

Standard Therapies

Diagnosis

DM1 is diagnosed by molecular genetic testing to determine the number of CTG repeats in the DMPK gene. Normal DMPK genes contain 5-35 CTG repeats. Individuals with genes containing 35-49 CTG repeats do not have DM1 but have an increased risk to have children with a larger number of CTG repeats who will have DM1. Genes with more than 50 CTG repeats are associated with symptoms of DM1.



DM2 is diagnosed by molecular genetic testing to determine the number of repeated copies of a portion of the ZNF9 gene. The number of repeated copies is not related to the age of onset of DM2, but symptoms appear to become more severe as the gene is passed from generation to generation.



Treatment

No specific treatment for the muscle weakness associated with myotonic dystrophy is available. Treatment is available for diabetes mellitus, cataracts and hypothyroidism. Affected individuals should be evaluated by a cardiologist because arrhythmias associated with myotonic dystrophy can be life threatening. Other specialists such as physiatrists, occupational therapists of physical therapists can make recommendations for assistive devices when necessary. Genetic counseling can be useful for families with this disorder. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.



For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



A "Muscle Wasting and Altered Metabolism" clinical trial sponsored by the National Center for Research Resources in the Department of Neurology at the University of Rochester has been completed. The Department of Neurology at the medical school of the University of Rochester is a site of significant research into these disorders. Two other noteworthy studies at the University of Rochester are currently (2005) ongoing:



1. A trial sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases is recruiting patients with myotonic dystrophy for the purpose of connecting them with medical researchers. Further information on this study is available by accessing the previously listed NIH site.



2. A study examining the cause of excessive sleepiness associated with myotonic dystrophy. For information contact:

James Hilbert

Phone: (585) 273-5590



Studies of the effectiveness of anti-arrhythmic and anti-convulsant drugs showed only very modest improvements as treatments for myotonic dystrophy. Selenium and Vitamin E have also been tested and may be helpful in increasing muscle strength and improvement of some other symptoms of this disorder. Overdoses of selenium and Vitamin E can be harmful (toxic), so treatment must be carefully monitored by a physician.

References

TEXTBOOK and MONOGRAPHS

Tohen JG., ed. Physicians' Guide to Rare Diseases. Mentale, NJ: Downed Publishing Company Inc; 1995:348.



Dubowitz Z., Muscle Disorders in Childhood. 2nd ed. Philadelphia, PA. W. B. Saunders Co; 1995.



Hamshere M, et al., Myotonic dystrophy. In: Rubinzstein DC, et al., Eds. Analysis of Triplet Repeat Disorders. Oxford, UK; BIOS Scientific Publishers Ltd: 1998.



REVIEW ARTICLES

Philips AV, et al., RNA processing and human disease. Cell Mol Life Sci. 2000;57:235-49.



Thornton C., The myotonic dystrophies. Semin Neurol. 1999;19:25-33.



Margolis RL, et al., Trinucleotide repeat expansion and neuropsychiatric disease. Arch Gen Psychiatry. 1999;56:1019-31.



Edstrom L., Dystrophia myotonica. Clinical, pathophysiological and molecular aspects. Scand J Rehabil Med Suppl. R1999;39:47-52.



JOURNAL ARTICLES

Vincent JB, et al., The unstable trinucleotide repeat story of major psychosis. Am J Med Genet. 2000;97:77-97.



Ugalde V, et al., Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Arch Phys Med Rehabil. 2000;81:472-78.



Sansone V, et al., Hypothyroidism unmasking proximal myotonic myopathy. Neuromuscul Disord. 2000;10:165-72.



Marchini A, et al., Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy. Clin Genet. 2000;57:74-82



Tanaka Y, et al., Congenital myotonic dystrophy: report of paternal transmission. Brain Dev. 2000;22:132-34.



Wieser T, et al., A family with PROMM not linked to recently mapped PROMM locus DM2. Neuromuscul Disord. 2000;10:141-43.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 160900; Last Update: 4/27/2000.

Resources

Muscular Dystrophy Association

3300 East Sunrise Drive

Tucson, AZ 85718-3208

USA

Tel: (520)529-2000

Fax: (520)529-5300

Tel: (800)572-1717

Email: mda@mdausa.org

Internet: http://www.mda.org/



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Myotonic Dystrophy Support Group

19-21 Main Road

Gedling

Nottingham, NG4 3HQ

United Kingdom

Tel: 01159875869

Tel: 01159870080

Email: contact@mdsguk.org

Internet: http://www.myotonicdystrophysupportgroup.org/



Myotonic Dystrophy Foundation

431 Burgess Dr.

Ste 200

Menlo Park, CA 94025

USA

Tel: (916)788-2626

Fax: (916)788-2646

Tel: (866)968-6642

Email: info@myotonic.org

Internet: http://www.myotonic.org



Child Neurology Foundation

2000 West 98th Street

Bloomington, MN 55431

USA

Tel: (952)641-6100

Fax: (952)881-6276

Tel: (877)263-5430

Email: jstone@childneurologyfoundation.org

Internet: http://www.childneurologyfoundation.org



Medical Home Portal

Dept. of Pediatrics

University of Utah

P.O. Box 581289

Salt Lake City, UT 84158

Tel: (801)587-9978

Fax: (801)581-3899

Email: mindy.tueller@utah.edu

Internet: http://www.medicalhomeportal.org



For a Complete Report

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