Muscular Dystrophy is a broad term that describes a genetically inherited disorder involving the muscles. One of the nine types of muscular dystrophy is Duchenne Muscular Dystrophy (DMD). DMD is a genetic disorder caused by a mutation in a gene on the X chromosome that prevents the production of dystrophin (1). This disorder is found primarily in boys and is characterized by progressive muscle degeneration and weakness. Overtime, the disease causes the muscle tissue to be broken down and eventually replaced by fatty deposits (pseudohypertrophy) (2). Due to the progressive deterioration of the muscles this disease will lead to paralysis and eventually death. The average life expectancy for patients afflicted with DMD is around 25 (3).

Guillaume Benjamin Amand Duchenne (1806–1875)

The disease is named for the pioneering 19th Century french neurologist Guillaume Benjamin Amand Duchenne. Although already known for his work in electrophysiology, Duchenne cemented his name in medical history with his contributions in the field of myopathies. In 1861, Duchenne described and detailed the first documented case of DMD. A few years later after becoming the first to obtain muscle biopsies from a living patient, Duchenne gave an account of thirteen other affected children.

Inheritance of DMD:
Duchenne Muscular Dystrophy is inherited in an X-linked recessive pattern. The gene associated with DMD is located on the X chromosome, which is one of the two sex chromosomes. Males only have one X chromosome, therefore, one altered copy of the gene in each cell is sufficient to cause the condition. Unlike males, females have two X chromosomes, so a mutation would have to occur in both copies of the gene to cause the disorder. Due to this fact, males are affected by X-linked recessive disorders much more frequently than females because it is unlikely that a mutation in both X chromosomes would occur (4). A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits onto their sons, because a father only passes on a Y chromosome to his son. In about two-thirds of c
Representation of Genetic Possibilites
ases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene (4). The other one-third of cases result from new mutations in the gene in affected males and are not inherited (4). In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness, cramping, and may be at a higher risk for cardiomyopathy (4). These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males.

Once inherited, mutations in the DMD gene (the largest known human gene) will result in a failure to provide instructions for making a protein called dystrophin. Dystrophin is one of many multiple proteins that are involved in the complex interactions of the muscle membrane and extracellular environment. It is a cytoskeleton protein located in the cardiac and skeletal muscle, where it helps stabilize and protect muscle fibers (4). More specifically, dystrophin and the dystrophin-associated glycoproteins (DAGs) are important elements for sarcolemmal stability (the integrity of the muscle), because they are responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal laminal Dystrophin betterlayer (6). In Ducheene's the absence of dystrophin leads to a drastic decrease in all the dystrophin related proteins, causing a disruption in the linkage between the subsarcolemmal and the extracellular matrix (4). This dystrophin deficiency will cause the muscles to weaken and become damaged over time, due to having to repeatedly contract and relax, leaving them susceptible to necrosis (4). Though it has been shown that dystrophin levels as low as 30% are sufficient enough to avoid DMD (7)
Duchenne muscular dystrophy is a progressive neuromuscular disorder. The main symptom of Duchenne muscular dystrophy is muscle weakness and muscle wasting. These symptoms will first present themselves in the voluntary muscles of the subject, specifically the muscles of the hips, pelvic area, thighs, shoulders, and calf muscles. Muscle weakness also occurs in the arms, neck, and other areas, but not as early as in the lower half of the body. The subject will also often present enlarged calves. These symptoms typically manifest themselves around age six and as early as infancy. Other physical symptoms of DMD are:
  • Lack of balance resulting in frequent falls
  • Difficulty with synergistic motor programs (running/jumping)
  • hyperlordosis of the spine, leading to shortening of hip-flexor muscles
  • Muscle Contractures of the achilles tendon and hamstrings
  • Pseudohypertrophy seen in the calf muscles and tongue
  • Loss of the ability to walk around age 12
  • Mental deficits (lower IQs) (8)
  • Eventually leads to death usually from cardiopulmonary complications
  • Unusual/awkward gait (8)
Duchenne traits
Characteristic traits of Duchenne
General Timeline of Duchenne

Muscle Weakness and Myopathies:
Muscle weakness if a very broad, generic, and sometimes over used term. In neurological practice, weakness means the loss of strength or power, manifesting in the inability to generate normal muscle force, operative word being normal (9). Muscle weakness can occur as a result to damage in any of the associated structures required for movement and the generation of muscle force. These structures are the upper motor neurons (neurons in the brain whose axons ascend the brain stem and spinal cord), the lower motor neurons (anterior horn cells), the peripheral nerves, the myoneural junction (the cholinergic synaps
Motor Pathway
Basic Motor Pathway (From UMN to LMN)
e between the lower motor neurons and the muscle fibers), and the muscle fibers (final contractile units) themselves (9). As stated before, the cause of DMD is a genetic mutation that leads to a decrease in the membrane protein called dystrophin which is responsible for maintaining sarcolemmal integrity. In dystrophin's absence muscle fibers begin to brake down causing structural damage to the contractile units and because of this damage muscle weakness sets in. Any muscle weakness due to inherited defects or damage to the muscle fibers like in DMD's case are referred to as myopathies, which literally means muscle disease. So, the resulting muscle weakness from DMD is not a result of damage in upper or lower motor neurons, the neuromuscular junction, or the peripheral nerves. In addition, the nervous system has the full ability to generate and conduct an action potential for voluntary movement and everything in the basic motor pathway (to the right) is fully capable of generating muscle force except for the final contractile units of the muscle fibers.

Signs and Tests:
Tests that aid in the diagnosis of Duchenne muscular dystrophy:
  • A positive Gower's test
  • Blood test (high levels of Creatine Kinase in the blood stream)
  • An electromyography (EMG) (shows the weakness is due to the destruction of muscles and not nerves)
  • Genetic testing
  • A muscle biopsy (confirms the absence of dystrophin)

Here is a video demonstrating a positive Gower's test:

Currently, there is no cure for DMD. Treatment is usually aimed at controlling the onset of symptoms to maximize the quality of life, and include the following:
  • Corticosteriods such as prednisolone increase energy and strength and defer severity of some symptoms (10)
  • Randomised control trials have shown that beta2-agonist increase muscle strength but do not modify disease progression (11)
  • Mild physical activity or physical therapy is advised
  • Orthopedic braces may help with walking
  • Proper respiratory support is necessary as disease progresses
  • Vascular targeted therapies (12).

Due to the progressive nature of the disease, Duchenne muscular dystrophy will eventually affect all voluntary muscles, as well as, respiratory and cardiac muscles. The disease is fatal and life expectancy is estimated to be 25 years, though this varies from patient to patient (3).

Duchenne muscular dystrophy is a progressive genetically inherited neurological disease usually found in boys, caused by a mutation of the X linked chromosome that prevents the production of dystrophin. Dystrophin is a cytoskeleton protein found in the skeletal and cardiac muscle that helps maintain sarcolemmal stability by connecting the cytoskeleton of each muscle fiber to the underlying basal laminal layer. As a result of the mutation of the DMD gene on the short arm of the X chromosome, there is a deficiency of dystrophin in the muscle fibers. This shortage of dystrophin leads to a disruption in the linkage between the subsarcolemmal and the extracellular matrix which will cause muscle fibers to become damaged over time after having to repeatedly contract and relax. Ultimately, resulting in necrosis. Once the muscle fibers have been structural damaged muscle weakness will set in. Because Ducheene muscular dystrophy results in muscle weakness due to a defect or damage in the muscle fibers it is considered a myopathy. Myopathy literally means muscle disease, and is indicative of DMD because the weakness experienced by the patient is a result of the wasting muscle fibers and not because of lesions or damages of the upper motor neurons, lower motor neurons, peripheral nerves, neuromuscular junction, or motor pathway. Symptoms of DMD include a waddling gait, enlarged calves, muscle weakness, and eventually paralysis. There is no known cure for Duchenne muscular dystrophy and life expectancy is estimated to be 25 years. The final cause of death is usually respiratory failure.


Dytrophin: Is a cytoskeleton protein located in the cardiac and skeletal muscle that is responsible for maintaining sarcolemmal stability.
Paralysis: is loss of muscle function for one or more muscles.
Pseudohypertrophy: the enlargement of a muscle due to muscle fibers being replaced by fatty deposits.
Sarcolemma: is the cell membrane of a striated muscle fiber cell.
Necrosis: is a form of cell injury that results in the premature death of cells in living tissue
Muscle weakness: inability to generate normal levels of muscle force – a reduction in strength
Muscle Force: force or tension generated as a result of muscle contraction
Upper Motor Neurons: neurons in the brain whose axons ascend the brain stem and spinal cord
Lower Motor Neurons: anterior horn cells
Myoneuronal Junction: the cholinergic synapse between the lower motor neurons and the muscle fibers

Suggested Further Readings/Resources

1) Short documentary on a boy with Duchenne muscular dystrophy

2) The facts of Duchenne muscular dystrophy

3) Recent study on vascular-targeted therapies as a possible cure for DMD


Multiple Choice:
1) In Duchenne muscular dystrophy a subject's muscle fibers are eventually replaced by what substance?

a) More muscle fibers that is why they have enlarged body segments
b) There muscle fibers do not get replaced they just waste away
c) Muscle fibers are replaced by fatty deposits; this is called pseudohypertrophy
d) The muscle fibers aren't actually replaced but all fast twitch muscle fibers are transformed into slow twitch muscle fibers

2) If a woman is a carrier of DMD and her husband does not have the trait, the possible outcomes of there child are?

a) Unaffected male
b) Carrier female
c) Affected female
d) Affected male
e) A, B, and D
f) all of the above

3) Females carriers of DMD can exhibit which of the following symptoms?

a) Muscle weakness
b) Cardiomyopathy
c) Blindness
d) A and B
c) Carriers only carry the mutation and wont exhibit any symptoms

4) Dystrophin's role in the muscle fiber is to?

a) Help calcium bind to troponin
b) To help phosphorylate ATP after muscle contraction
c) It is the binding site for acetylcholine at the neuromuscular junction
d) To help maintain the integrity and stability of the sarcolemma

5) All of the following are symptoms of Duchenne muscular dystrophy except:

a) Muscle weakness
b) Pseudohypertrophy
c) Paresthesia in the distal extremities
d) Hyperlordosis
c) All of the above

True or False:
6) A myopathy is any disease that results in muscular weakness due to the damage of upper or lower motor neurons?

7) The average life expectancy of a patient suffering from DMD is 15 years?

8) The most common type of gait pattern associated with DMD is known as an Equine gait?

9) A patient suffering from DMD exhibits muscle weakness but not because of their inability to initiate an action potential?

10) Weakness caused by DMD typically affects the proximal muscles of the arms first and then progresses to the distal limbs of the leg?

Short Answer:
1) Describe what affect a deficiency in dystrophin has on the muscle fibers?
2) Discuss the timeline or prognosis of DMD?
3) What does a positive Gower's test show?

Multiple Choice:
1) C; 2) E; 3) D; 4) D; 5) C

True or False:
6) F; 7) F; 8) F; 9) T 10) T

Short Answer:
1) Dystrophin is a cytoskeleton protein used to maintain the integrity of the sarcolemma by maintaining the linkage between the cytoskeleton of each muscle fiber and the underlying basal lamina layer. Without sufficient amounts of this protein the muscle fibers will undergo structural damage leading to muscle weakness and eventually necrosis.

2) A person with Duchenne muscular dystrophy will exhibit walking difficulties as early as 2 to 3 years old. Typically, by age 12 they will become wheel chair dependent. At this time they will start to succumb to skeletal deformities. Around age 13 they will lose most if not all use of their arms. By age 20 they will become ventilation dependent at night and most likely during all 24 hours of the day. Average life expectancy is 25 years.

3) A positive Gower's test depicts how a person with DMD has to get up from a sitting or laying position. The patient will have to lay flat on their stomachs and spread their legs as they walk themselves up with their hands to a standing position. If a person follows this typical pattern as they attempt laying to stand routine it is a good indication of DMD.

(numbering corresponds to the in-text citations above)

1) Medicine Net. (2013, August). Definition of muscular dystrophy. [Online] Retrieved from http://www.medterms.com/script/main/art.asp?articlekey=11686
2) Fighting Muscle Disease (MDA). Duchenne muscular dystrophy. [Online] Retrieved (12/13/2013) from http://mda.org/disease/duchenne-muscular-dystrophy/overview
3) Kaneshiro, Neil K. et al., (2012, January). Duchenne muscular dystrophy: MedlinePlus Medical Encyclopedia. [Online] Retrieved (12/17/2013) from http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm
4) Genetics Home Reference. (2012, February). Duchenne and Becker muscular dystrophy. [Online] Retrieved (12/17/2013) from http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy
5) Matsumura, K. et al., (1993). Deficiency of dystrophin-associated proteins in Duchenne muscular dystrophy patients lacking COOH-terminal domains of dystrophin. The Journal of Clinical Investigation, 92, 866-871. http://www.jci.org/articles/view/116661/pdf
6) Waite A, Tinsley CL, Locke M, Blake DJ. The neurobiology of the dystrophin-associated glycoprotein complex. Ann Med. Jan 26 2009;1-16. http://www.ncbi.nlm.nih.gov/pubmed/19172427
7) Neri M, et al., Dystrophin levels as low as 30% are suffiecient enough to avoid muscular dystrophy in the human, Neuromuscular Disorders (2007), http://www.parentprojectmd.org/site/DocServer/dystrophin_levels.pdf?docID=2961
8) Twee T Do. (2012 September). Muscular Dystrophy. [Online] Retrieved (12/17/2013) from http://emedicine.medscape.com/article/1259041-overview#a0104
9) Reeves, Alexander G, Swenson, Rand S., (2008). Evaluation of a patient with weakness. Darthmouth Medical School. [Online] Retrieved (12/17/2013) from http://www.dartmouth.edu/~dons/part_2/chapter_12.html
10) Mendell, J.R. et al., (1989). Randomized, double-blind six-Month trial of prednisone in Duchenne's muscular dystrophy. The New England Journal of Medicine, 320, 1592-1597. http://www.nejm.org/doi/full/10.1056/NEJM198906153202405
11) Wikipedia., Duchenne muscular dystrophy. Last modified (2013, November). Retrieved (12/17/2013) from http://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy#cite_note-13
12) Ennen, James P, et al., (2013 April). Vascular-targeted therapies for duchenne muscular dystrophy. Skeletal Muscle Journal (2013), http://www.skeletalmusclejournal.com/content/3/1/9

Image Links: In order of appearence (can access image URL by clicking on the image)
1) http://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy
2) http://mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance
3) http://mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance
4) http://www.healthandfitnesstalk.com/tag/duchenne-muscular-distrophy/
5) http://prosensa.eu/patients-and-family/duchenne-muscular-dystrophy
6) http://www.bioon.com/bioline/neurosci/course/basmot.html