55 Kenosia Avenue
Danbury, CT 06810
Phone: 203.744.0100
Toll Free: 1.800.999.6673
http://rarediseases.org

Dystrophy, Myotonic

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1987, 1988, 1990, 1994, 2000, 2001, 2002, 2005, 2007

Synonyms of Dystrophy, Myotonic

Disorder Subdivisions

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.

Related Disorders

Myotonia congenita or Thomsen's disease is a rare inherited disorder that begins early in life and involves the entire muscle system. Difficulty in initiating movement and slow muscle relaxation are the chief symptoms. Muscle stiffness of the entire body may also occur with this generally nonprogressive disorder. (For more information, choose "Thomsen" as your search term in the Rare Disease Database.)

Inclusion body myositis (IBM) is a rare inflammatory muscular disorder that usually becomes apparent during adulthood. The disorder presents as slow progressive weakness and withering away (atrophy) of the muscles (myositis), especially of the arms and legs.

IBM is characterized by the gradual onset (over months or years) of muscle fatigue and weakness; a clear tendency to strike men more frequently than women; and affecting both the muscles closest to the body's trunk (proximal) and those farthest from the trunk (distal). Onset is usually after age 50, although it may occur earlier. (For more information, choose "myositis" as your search term in the Rare Disease Database.)

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.

Organizations related to Dystrophy, Myotonic

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.

Report last updated: 2007/07/23 00:00:00 GMT+0