• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
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Duchenne Muscular Dystrophy

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Last updated: 01/18/2024
Years published: 1985, 1988, 1989, 1992, 1994, 1997, 1998, 1999, 2000, 2007, 2012, 2016


Acknowledgment

NORD gratefully acknowledges Gyula Acsadi, MD, PhD, Professor of Pediatrics, University of Connecticut, School of Medicine, Chief of Neurology Division, Connecticut Children’s Medical Center, for assistance in the preparation of this report.


Disease Overview

Summary

Duchenne muscular dystrophy (DMD) is a rare muscle disorder but it is one of the most frequent genetic conditions affecting approximately 1 in 3,500 male births worldwide. It is usually recognized between three and six years of age. DMD is characterized by weakness and wasting (atrophy) of the muscles of the pelvic area followed by the involvement of the shoulder muscles. As the disease progresses, muscle weakness and atrophy spread to affect the trunk and forearms and gradually progress to involve additional muscles of the body. In addition, the calves appear enlarged in most patients. The disease is progressive and most affected individuals require a wheelchair by the teenage years. Serious life-threatening complications may ultimately develop including disease of the heart muscle (cardiomyopathy) and breathing (respiratory) difficulties.

DMD is caused by changes (variants) of the DMD gene on the X chromosome. The gene regulates the production of a protein called dystrophin that is found in association with the inner side of the membrane of skeletal and cardiac muscle cells. Dystrophin is thought to play an important role in maintaining the membrane (sarcolemma) of muscle cells.

Introduction

Muscular dystrophies are characterized by specific abnormalities (e.g. variation of muscle fiber size, muscle fiber necrosis, scar tissue formation and inflammation) in muscle biopsy from the patients. Approximately 30 different genetic conditions make up the muscular dystrophies. DMD is classified as a dystrophinopathy. The dystrophinopathies are a spectrum of muscle diseases, each caused by alterations in the dystrophin gene. The most severe end of the spectrum is known as Duchenne muscular dystrophy lacking completely dystrophin protein. Decreased or truncated dystrophin protein is associated with less severe form is Becker muscular dystrophy.

The clinical hallmarks of DMD include weakness and wasting of various voluntary muscles of the body. In most advanced stages of the disease, the heart and gut muscles will be affected.

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Synonyms

  • DMD
  • dystrophinopathy
  • pseudohypertrophic myopathy
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Signs & Symptoms

DMD usually becomes apparent early during childhood. Affected children develop weakness and wasting (atrophy) of the muscles closest to the trunk (proximal muscles) such as those of the upper legs and pelvic area and upper arms and shoulder area. However, a few other muscles appear disproportionally bulky. As the disease progresses, muscle weakness and atrophy spread to affect the lower legs, forearms, neck and trunk. The rate of progression is quite similar from person to person but individual variation may happen.

In children with DMD, initial findings may include delays in reaching developmental milestones such as sitting or standing without assistance; toe walking; an unusual, waddling manner of walking (gait); difficulty climbing stairs or rising from a sitting position (Gower’s sign); and repeated falling. Toddlers and young children may seem awkward and clumsy and may exhibit abnormal enlargement of the calves due to scarring of muscles (pseudohypertrophy). Parents may be falsely encouraged by an apparent improvement between the ages of 3 and 5, but this may be due to natural growth and development. As the disease progresses, additional abnormalities may develop such as progressive curvature of the spine (scoliosis or lordosis), wasting of thigh and pectoral muscles, and abnormal fixation of certain joints (contractures). A contracture occurs when thickening and shortening of tissue such as muscle fibers causes deformity and restricts movement of affected areas, especially the joints. Without physical therapy treatment, leg braces may be needed by age 8-9 to assist affected individuals to walk. By approximately ages 10 to 12, most affected individuals require a wheelchair.

Children with DMD have reduced bone density and an increased risk of developing fractures of certain bones, such as hips and spine. Many affected individuals will display mild to moderate degrees of non-progressive intellectual impairment and learning disabilities.

By the late teens, DMD may also be characterized by additional potentially life-threatening complications including weakness and deterioration of the heart muscle (cardiomyopathy). Cardiomyopathy can result in impairment in the ability of the heart to pump blood, irregular heartbeats (arrhythmias), and heart failure. Another serious complication associated with DMD is weakness and deterioration of muscles in the rib cage. This can result in an increased susceptibility to respiratory infections (e.g., pneumonia), difficulty coughing, and, ultimately, respiratory failure.

Involvement of muscles within the gastrointestinal tract may result in dysmotility, a condition in which the passage of food through the digestive tract usually because of slow and uncoordinated movements of the muscles of the digestive tract. Gastrointestinal dysmotility may result in constipation and diarrhea.

One third of patients with DMD may have various degree of cognitive impairment including learning disability, attention deficit and autistic spectrum disorder.

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Causes

DMD is caused by variants of the DMD gene located on the X chromosome. The DMD gene regulates (encodes for) the production of dystrophin, a protein that appears to play an essential role in maintaining the integrity of cell membrane in skeletal (voluntary) and cardiac muscle cells. Dystrophin is found attached to the inner side of the membrane that surrounds muscle fibers. Variants of the DMD gene will result in absence of the dystrophin protein, leading to degeneration of muscle fibers. The body can replace (regenerate) some muscle fibers, but over time more and more muscle fiber is lost. Such degeneration leads to the symptoms and findings associated with DMD. In Becker muscular dystrophy, a related disorder, dystrophin is present, but it is smaller than normal or only present in insufficient levels to function properly.

DMD is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by a mutated gene on the X chromosome and mostly affect males. Females who have a mutated gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the mutated gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a mutated gene, he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder can reproduce, he will pass the mutated gene to all his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male children.

Some females who inherit a single copy of the a DMD gene variant may have some symptoms associated with DMD such as weakness of certain muscles, especially those of the arms, legs and back. Carrier females who develop symptoms of DMD are also at risk for developing heart abnormalities, which may result in exercise intolerance or shortness of breath. If left untreated, heart abnormalities can cause life-threatening complications in affected females.

Although most boys with DMD inherit the DMD gene variant from their mothers, some may develop the disease as the result of a spontaneous mutation of the DMD gene that occurs randomly for unknown reasons (de novo or sporadic cases).

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Affected populations

DMD is the most common childhood onset form of muscular dystrophy and affects males almost exclusively. The birth prevalence is estimated to be 1 in every 3,500 live male births. Age of onset is usually between 3 and 5 years of age. The muscular dystrophies as a whole are estimated to affect 250,000 individuals in the United States.

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Diagnosis

A diagnosis of DMD is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including molecular genetic tests. If the genetic tests are not informative, surgical removal and microscopic examination (biopsy) of affected muscle tissue that may reveal characteristic changes to muscle fibers. Specialized blood tests (e.g. creatine kinase) that evaluate the presence and levels of certain proteins in muscle (immunohistochemistry) are also used.

Molecular genetic tests involve the examination of DNA to identify disease-causing variants in the DMD gene.

Blood tests may reveal elevated levels of the creatine kinase (CK), an enzyme that is found in abnormally high levels when muscle is damaged. The detection of elevated CK levels (usually in the thousands or ten thousands range) can confirm that muscle is damaged or inflamed, but cannot confirm a diagnosis of DMD.

In some cases, a specialized test can be performed on muscle biopsy samples that can determine the presence and levels of specific proteins within cells. Various techniques such as immunostaining, immunofluorescence or Western blot (immunoblot) can be used. These tests involve the use of certain antibodies that react to certain proteins such as dystrophin. Tissue samples from muscle biopsies are exposed to these antibodies and the results can determine whether a specific muscle protein is present in the cells and in what quantity or what size.

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Standard Therapies

Treatment
No curative treatment exists for DMD. Treatments are aimed at the specific symptoms present in each individual. Treatment options should include physical therapy and active and passive exercise to build muscle strength and prevent contractures. Surgery may be recommended in some patients to treat contractures or scoliosis. Braces may be used to prevent the development of contractures. The use of mechanical aids (e.g., canes, braces, and wheelchairs) may become necessary to aid walking (ambulation).

Corticosteroids are used as standard of care to treat individuals with DMD. These drugs slow the progression of muscle weakness in affected individuals and delay the loss of ambulation by 2-3 years. Two common corticosteroid drugs used to treat individuals with DMD are prednisone and deflazacort (which is not available in the United States). In 2023, the corticosteroid vamorolone (Agamree) was FDA approved to treat patients with DMD two years of age and older.

In 2016, eteplirsen (Exondys 51 ) was approved by the U.S. Food and Drug Administration (FDA) to treat DMD and is the first drug approved for this condition. Exondys 51 is specifically indicated for patients who have a confirmed variant of the DMD gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.

In 2017, deflazacort (Emflaza) was FDA approved to treat patients age 5 years and older with DMD.

In 2019 and 2020 respectively, the FDA approved golodirsen (Vyondys 53) and viltolarsen (Viltepso) to treat patients with DMD who have a confirmed variant of the DMD gene that is amenable to exon 53 skipping, which affects about 8 percent of patients with DMD.

In 2021, the FDA approved casimersen (Amondys 45) to treat patients with DMD who have a confirmed variant of the DMD gene that is amenable to exon 45 skipping. This variant occurs in approximately 8 percent of patients with DMD. Amondys 45 is the first FDA-approved targeted treatment for patients with this type of gene variant.

In 2023, the FDA approved the first gene therapy for DMD. Elevidys was approved to treat children aged 4-5 who have a confirmed variant in the DMD gene.

Clinical Testing and Work-Up
Children diagnosed with DMD should be monitored regularly for potential heart involvement. In some individuals, severe respiratory distress may necessitate the use of ventilator to assist breathing.

Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.

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Clinical Trials and Studies

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 web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Contact for additional information about Duchenne muscular dystrophy:
Gyula Acsadi, MD, PhD
Professor of Pediatrics
University of Connecticut, School of Medicine
Chief of Neurology Division
Connecticut Children’s Medical Center
282 Washington Street
Hartford, CT. 06106
Phone: 860-837-7500
Fax: 860-837-7550

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References

TEXTBOOKS
Behrman RE, Kliegman RM, Jenson HB,eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, PA: Elsevier Saunders; 2005:2060-9.

Acsadi G. Duchenne Muscular Dystrophy. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins: 2003:623.

JOURNAL ARTICLES

Foster K, Foster H, Dickson JG. Gene therapy progress and prospects: Duchenne muscular dystrophy. Gene Ther. 2006;13:1677-85.

Flanigan KM, von Niederhausern A, Dunn DM, et al., Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet. 2003;72:931-9.

Davies JE, Winokur TS, Aaron MF, et al., Cardiomyopathy in a carrier of Duchenne’s muscular dystrophy. J Heart Lung Transplant. 2001;20:781-4.

Fenichel GM, Griggs RC, Kissel J, et al., A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne muscular dystrophy. Neurology. 2001;56:1075-9.

Dubowitz V. The muscular dystrophies–clarity or chaos? N Engl J Med. 1997;336:650-651.

Boland BJ, Silbert PL, Groover RV, Wollan PC, Silverstein MD. Skeletal, cardiac, and smooth muscle failure in Duchenne muscular dystrophy. Pediat Neurol. 1996;14:7-12.

Bushby KMD, Appleton R, Anderson LVB, et al. Deletion status and intellectual impairment in Duchenne muscular dystrophy. Dev Med Child Neurol. 1995;37:260-269.

Barbujani G, Russo A, Danieli GA, et al. Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases. Hum Genet. 1990;84: 522-526.

Mendell JR, Moxley RT, Griggs RC, et al. Randomized, double-blind six-month trial of prednisone in Duchenne’s muscular dystrophy. N Engl J Med. 1989;320:1592-1597.

INTERNET
Darras BT, Miller DT, Urion DK. Dystrophinopathies. 2000 Sep 5 [Updated 2014 Nov 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1119/ Accessed June 21, 2016.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Muscular Dystrophy, Duchenne Type; DMD. Entry No: 310200. Last Update 6/06/2016. Available at: https://omim.org/entry/310200 Accessed June 21, 2016.

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Programs & Resources

RareCare® Assistance Programs

Duchenne Muscular Dystrophy Medical Assistance
Temporarily Waitlisting
Phone: 866-218-8172 Fax: 203-263-9597
Resource(s): DMD-PAP
Duchenne Muscular Dystrophy Premium Copay Assistance
Temporarily Waitlisting
Phone: 866-218-8172 Fax: 203-263-9597
Resource(s): DMD-PAP

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations


National Organization for Rare Disorders