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Duchenne muscular dystrophy

Duchenne muscular dystrophy
Classification & external resources
ICD-10 G71.0
ICD-9 359.1
OMIM 310200
DiseasesDB 3985
MeSH D020388

Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy that is characterized by decreasing muscle mass and progressive loss of muscle function in male children. This disorder is caused by a mutation in a specific gene within the X chromosome that provides instructions for the formation of the dystrophin protein, an important component of muscle tissue. Females can be carriers but generally do not experience the symptoms of the condition.

Symptoms usually appear in male children before age 6 and may occur as early as infancy. Progressive muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed and eventually spreads to the arms, neck, and other areas. Early signs may include enlarged calf muscles (pseudohypertrophy), low strength and endurance levels, and difficulties in standing up and walking on stairs. As the condition progresses, muscle tissue experiences wasting and fibrosis, and is eventually replaced by fat and connective tissue. By age 10, braces may be required for walking, and most patients are confined to a wheelchair by age 12. Later symptoms include contractures, abnormal bone development that leads to skeletal deformities including curvature of the spine, complete loss of movement, and increasing difficulty in breathing. Intellectual impairment may also be present but does not progress as the child ages. The condition is terminal and death usually occurs before the age of 30.

Duchenne muscular dystrophy occurs in approximately 2 out of 10,000 people and can either be inherited or occur spontaneously. A family history of Duchenne muscular dystrophy is a significant risk factor.

DMD is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806-1875), who first described the disease in the 1860s.



Duchenne muscular dystrophy is a type of dystrophinopathy which includes a spectrum of muscle disease caused by mutations in the Xp21 gene, which encodes the protein dystrophin. The large size of the gene makes it prone to mutation, causing DMD to occur spontaneously in many families without a history of the disease. In Duchenne muscular dystrophy, genetic instructions are not sufficient to create a stable dystrophin protein, resulting in a complete absence of dystrophin. Becker's muscular dystrophy is a milder type of dystrophinopathy where a stable but mutated form of the protein results from the reading of the gene.

Duchenne muscular dystrophy is inherited in an X-linked recessive pattern. Male children, who have an XY chromosome pair, receive one of their mother's two X chromosomes and their father's Y chromosome. Women DMD carriers who have an abnormal X chromosome have a one-in-two risk of passing that abnormality on to their male children. Unlike most female children, a male child with an inherited defective Xp21 gene does not have a second X chromosome to provide correct genetic instructions, and the disease manifests.

The sons of carrier females each have a 50% risk of having the disease, and the daughters each have a 50% risk of being carriers. Daughters of men with Duchenne will always be carriers, since they will inherit an affected X chromosome from their father (note that the diagram only shows the results from an unaffected father). Some females will also have very mild degrees of muscular dystrophy, and this is known as being a manifesting carrier. In one-third of the cases, the disease is a result of an unspontaneous or new mutation.[1]

Prenatal testing, such as amniocentesis, for pregnancies at risk is possible if the DMD disease-causing mutation has been identified in a family member or if informative linked markers have been identified.

The dystrophin gene contains 24 regions of 109 amino acids that are similar but not exact, making it susceptible to misalignment at the meiotic synapse, which can lead to frameshift mutations and an untranslatable gene. This can happen with a frequency of about 1 in 10,000.

In some female cases, DMD is caused by skewed X inactivation. In these cases, two copies of the X chromosome exist, but for reasons currently unknown, the flawed X chromosome manifests instead of the unflawed copy. In these cases, a mosaic form of DMD is seen, in which some muscle cells are completely normal while others exhibit classic DMD findings. The effects of a mosaic form of DMD on long-term outlook is not known.


Duchenne muscular dystrophy is caused by a mutation of the dystrophin gene whose protein product is responsible for the connection of muscle fibers to the extracellular matrix through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (cell membrane). In a complex cascading process involving several pathways that is not clearly understood, increased oxidative stress within the cell damages the sarcolemma, eventually results in the death of the cell. Muscle fibres undergo necrosis and are ultimately replaced with adipose and connective tissue.


The main symptom of Duchenne muscular dystrophy is rapidly progressive muscle weakness associated with muscle wasting with the proximal muscles[citation needed] being first affected, especially the pelvis and calf muscles. Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body. Symptoms usually appear before age 6 and may appear as early as infancy. Generalized weakness and muscle wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged. The other physical symptoms are:

  • Awkward gait (patients tend to walk on their forefeet, because of an increased calve tonus)
  • Frequent falls
  • Difficulty with motor skills (running, hopping, jumping)
  • Progressive difficulty walking
  • Eventual loss of ability to walk (usually by the age of 12)
  • Fatigue
  • Higher risk of behaviour and learning difficulties.
  • Skeletal deformities (including scoliosis in some cases)
  • Muscle deformities
  • Pseudohypertrophy of tongue and calf muscles. The enlarged muscle tissue is eventually replaced by fat and connective tissue, hence the term pseudohypertrophy.
  • Muscle contractures of heels and legs, rendering them unusable because the muscle fibers shorten and fibrosis occurs in connective tissue

Signs and tests

Muscle wasting begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy may occur, but the development of congestive heart failure or arrhythmias (irregular heartbeats) is rare.

  • A positive Gower's sign reflects the more severe impairment of the lower extremities muscles. The child helps himself to get up with upper extremities: first by rising to stand on his arms and knees, and then "walking" his hands up his legs to stand upright.
  • Affected children usually tire more easily and have less overall strength than their peers.
  • Creatine kinase (CPK-MM) levels in the bloodstream are extremely high.
  • An electromyography (EMG) shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.
  • Genetic testing can reveal genetic errors in the Xp21 gene.
  • A muscle biopsy (immunohistochemistry or immunoblotting) or genetic test (blood test) confirms the absence of dystrophin, although improvements in genetic testing often make this unnecessary.


CPK test

If a physician suspects DMD after examining the boy they will use a CPK (creatine phosphokinase) test to determine if the muscles are damaged. This test measures the amount of CPK in the blood. In DMD patients CPK leaks out of the muscle cell into the bloodstream, so a high level (nearly 50 to 100 times more) confirms that there is muscle damage. Affected individuals may have a value as high as 15,000 to 35,000iu/l (normal = 60iu/l).

DNA test

The dystrophin gene is composed of 79 exons, and DNA testing and analysis can usually identify the specific type of mutation and the exon or exons that are affected. DNA testing confirms the diagnosis in most cases.[2]

Muscle biopsy

If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted and a dye is applied that reveals the presence of dystrophin. Complete absence of the protein indicates the condition.

Over the past several years DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of Duchenne's.

Prenatal tests

If one or both parents are 'carriers' of a particular condition there is a risk that their unborn child will be affected by that condition. 'Prenatal tests' are carried out during pregnancy, to try to find out if the fetus (unborn child) is affected. The tests are only available for some neuromuscular disorders. Different types of prenatal tests can be carried out after about 10 weeks of pregnancy. Chorion villus sampling (CVS) can be done at 10-12 weeks, and amniocentesis at about 14-16 weeks, while placental biopsy and foetal blood sampling can be done at about 18 weeks. Women and/or couples need to consider carefully which test to have and to discuss this with their genetic counselor. Earlier testing would allow early termination which would probably be less traumatic for the couple, but it carries a slightly higher risk of miscarriage than later testing (about 2%, as opposed to 0.5%).


There is no known cure for Duchenne muscular dystrophy yet although recent stem-cell research is showing some ways to replace damaged muscle tissue. Treatment is generally aimed at control of symptoms to maximize the quality of life.

  • Corticosteroids such as prednisone and deflazacort increase energy and strength and defer severity of some symptoms.
  • Mild, non-jarring physical activity such as swimming is encouraged. Inactivity (such as bed rest) can worsen the muscle disease.
  • Physical therapy is helpful to maintain muscle strength, flexibility, and function.
  • Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care. Form-fitting removable leg braces that hold the ankle in place during sleep can defer the onset of contractures.
  • Appropriate respiratory support as the disease progresses is important


Duchenne muscular dystrophy eventually affects all voluntary muscles and involves the heart and breathing muscles in later stages. Survival is rare beyond the early 30s,[3] although recent advancements in medicine are extending the lives of those afflicted. Death typically occurs from respiratory failure or heart disorders.

Physical Therapy

Physical therapists are concerned with enabling children to reach their maximum physical potential. Their aim is to:

  • minimize the development of contractures and deformity by developing a programme of stretches and exercises where appropriate
  • anticipate and minimize other secondary complications of a physical nature
  • monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

Mechanical Ventilatory/Respiration Assistance: Volume Ventilators/Respirators

Modern "volume ventilators/respirators," which deliver an adjustable volume (amount) of air to the person with each breath, are valuable in the treatment of people with muscular dystrophy related respiratory problems. Ventilator treatment usually (but not always) begins in the mid to late teens when the respiratory muscles begin to fail.

When the vital capacity has dropped below 40 percent of normal, a volume ventilator/respirator may be used during sleeping hours, a time when the person is most likely to be under ventilating ("hyperventilating"). Hyperventilation during sleep is determined by a thorough history of sleep disorder with an oximetry study and a capillary blood gas (See Pulmonary Function Testing). The ventilator requires an endotracheal or tracheostomy tube through which air is directly delivered.

As the vital capacity declines to less than 30 percent of normal, a volume ventilator/respirator may also be needed during the day for more assistance. The person gradually will increase the amount of time using the ventilator/respirator during the day as needed. A tracheostomy tube is used in the daytime and during sleep. The machine can easily fit on a ventilator tray on the bottom or back of a power wheelchair with an external battery for portability.

Researching a cure

Promising research is being conducted around the globe to find a cure, or at minimum a therapy that is able to mitigate some of the devastating effects of the disease. Finding a cure is made more complex by the number and variation of genetic mutations in the dystrophin gene that result in DMD.

In the area of stem cell research, a recent paper was published in Nature Cell Biology that describes the identification of pericyte-derived cells from human skeletal muscle. These cells have shown to fulfill important criteria for consideration of therapeutic uses. That is, they are easily accessible in postnatal tissue, they are able to grow to a large enough number in vitro to provide enough cells for systemic treatment of a patient, they have been shown to differentiate into skeletal muscle, and, very importantly, they can reach skeletal muscle through a systemic route. This means that they can be injected arterially and cross through arterial walls into muscle, unlike past hopeful therapeutic cells such as muscle satellite cells which require the impractical task of intramuscular injection. These findings show great potential for stem cell therapy of DMD. In this case a small biopsy of skeletal muscle from the patient would be collected, the pericyte-derived cells would be extracted and grown in culture, and then these cells would be injected into the blood stream where they could navigate into and differentiate into skeletal muscle.

The research group of Kay Davies works on the upregulation of utrophin, a smaller but similar protein that is found in fetal humans, as a substitute for dystrophin.

At the Généthon Institute in Evry near Paris under Olivier Danos and Luis García the U7 gene transfer technique is under development. This new technique is a combination of exon skipping and the transfer of a gene that instructs the muscle cells to continuously produce the antisense oligonucleotides (AONs) themselves so that they do not have to be injected repeatedly. The AONs are potential drugs which are able to modify the genetic information in such a way that the fast progressing Duchenne muscular dystrophy is converted into the much slower developing Becker muscular dystrophy. Early research into the effects of U7 Gene Transfer[4] have been very promising. Treated mice have gone on to show very little muscle weakness even after being stressed. Treated monkeys have retained the active AONs 6 years after injection, and treated dogs have developed 80% of the normal muscle mass within 2 months of treatment. First round tests in humans are due to begin soon, but given the need for multiple rounds of testing before a treatment can be released to the public, it will be at least a few years before this cure is widely available (if indeed these results are possible in humans).

Antisense techniques can also modify splicing of pre-mRNA, similarly converting Duchenne to Becker-like muscular dystrophy in animal models but without the need for insertion of DNA by virus. Because these techniques do not permanently modify the DNA, they are more accurately considered as potential treatments rather than cures. Especially promising for this application are Morpholino antisense oligos.[5][6][7] Morpholinos are commencing Phase 1 clinical trials in the EU.[8]

More information on the new PTC124 trials, currently nearing the end of Phase II, is available at the website. This potential treatment would address from 5 to 15 percent of DMD cases where the dystrophin protein cannot be completed due to an incorrect stop codon in the genetic sequence. The PTC124 treatment skips the improper "stop" instruction, allowing reading through of the remaining sequence and completion of the dystrophin protein assembly process. In recent mouse trials, PTC124 was found to repair damaged muscle tissues.[9][10]

Recent research shows losartan, a currently available drug used for treating hypertension, to be effective in halting the progress of the disease in mice that were genetically engineered to have Duchenne's.[11] Human trials are in planning.

Some parents of children with Duchenne's are noting reductions of symptomatic severity from a regimen of Protandim, a non-prescription nutritional supplement that increases levels of two specific antioxidant enzymes. Other parents report no benefit. Controlled clinical trials have not yet been conducted, and parent observations may have been influenced by confounding factors such as expectation bias, normal developmental progress, and the common practice of implementing additional nutritional supplements and/or corticosteroids concurrent with the Protandim. However, Protandim is promising on a theoretical level, in that it has the potential to modify the inflammatory/cell death cycle. DMD mouse-model trials of the therapy are in progress, and human trials are planned.[12][13]

Research from a group in France led by L. Ségalat has identified a number of drugs that are currently licenced for other applications as halting or reducing dramatically the advance of muscle degeneration in a worm model of DMD. They are now using mouse models to confirm these findings, which so far are looking very promising, confirming the efficacy of these drugs. However, work in mice seems to be moving slowly. The main classes of drugs they identified where SSRI (ie antidepressants such as prozac) and muscle relaxants, such as those used by athletes after heavy training. There is conflicting evidence from animal models suggeseting that doing less exercise slows down the rate of degeneration of the muscle; therefore there is a possibility that both these drugs act somewhat as sedatives, although the reality seems to be that the worms and mice are more active overall, as they have less muscle damage and so can remain active for much longer.


Genetic counseling is advised for people with a family history of the disorder. Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.

Organizations specific to DMD

In addition to charities devoted to muscular dystrophies in general (such as MDA), these charities are devoted exclusively to DMD:

  • Parent Project Muscular Dystrophy: Parent Project Muscular Dystrophy’s mission is to improve the treatment, quality of life and long-term outlook for all individuals affected by Duchenne muscular dystrophy (DMD) through research, advocacy, education and compassion.
  • Charley's Fund: an organisation whose mission is to fund research for cure or treatment for Duchenne. Charley's Fund invests money in translational research – research that focuses on moving science from the lab into human clinical trials.
  • JettFund ( , ): Currently, 25 teens are biking across America to raise funds for teens with DMD. The recent film Darius Goes West (2007) is a documentary of Darius Weems who suffers from DMD and is taken on a road trip by eleven friends to have MTV "pimp his ride".
  • CureDuchenne: is a non-profit organization that aggressively funds leading edge research for treatments and a cure for Duchenne muscular dystrophy. Catchpenny, a band from the mid-west, has written a song for CureDuchenne called "Chance for a Lifetime." Catchpenny performs across the country raising Duchenne awareness. Hear it on CureDuchenne's website


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  5. ^ McClorey G, Moulton H, Iversen P, Fletcher S, Wilton S (2006). "Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD". Gene Ther 13 (19): 1373-1381. PMID 16724091.
  6. ^ McClorey G, Fall A, Moulton H, Iversen P, Rasko J, Ryan M, Fletcher S, Wilton S (2006). "Induced dystrophin exon skipping in human muscle explants". Neuromuscul Disord 16 (9-10): 583-590. PMID 16919955.
  7. ^ Fletcher S, Honeyman K, Fall AM, Harding PL, Johnsen RD, Steinhaus JP, Moulton HM, Iversen PL, Wilton SD (2007). "Morpholino Oligomer-Mediated Exon Skipping Averts the Onset of Dystrophic Pathology in the mdx Mouse". Mol Ther. [Epub ahead of print]. PMID 17579573.
  8. ^ conducted by the MDEX consortium
  9. ^
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  12. ^
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Further reading

  • Carre-Pierrat M, Mariol MC, Chambonnier L, Laugraud A, Heskia F, Giacomotto J, Ségalat L. "Blocking of striated muscle degeneration by serotonin in C. elegans". Journal of Muscle Research and Cell Motility 2006; 27(3-4): 253-8. PMID: 16791712
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Duchenne_muscular_dystrophy". A list of authors is available in Wikipedia.
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