muscular dystrophy

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A group of muscle diseases that are hereditary and characterized by progressive muscle weakness and wasting.

The muscular dystrophies are primary diseases of the muscle cells characterized by progressive degeneration and replacement by fibrous tissue, resulting in progressive muscle weakness. In some types of muscular dystrophies, the disease appears to be restricted to the skeletal muscles alone (facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy), and in others skeletal-muscle involvement is a part of a more generalized process, with abnormalities in other organ systems as well (Duchenne's muscular dystrophy, myotonic dystrophy). These features as well as the differing patterns of inheritance indicate that the various muscular dystrophies are different diseases with different genetic and biochemical abnormalities underlying them.

The gene for the Duchenne and the Becker muscular dystrophy has been identified. This gene produces the muscle protein dystrophin, which is absent in Duchenne's dystrophy and qualitatively altered in Becker's dystrophy. Although the gene for myotonic dystrophy has not been identified, it has been found to be closely linked to genetic markers on chromosome 19. See also Human genetics; Muscle proteins.

Duchenne's muscular dystrophy is the most rapidly progressive form of muscular dystrophy. It affects boys before the age of 4, and is characterized initially by progressive weakness of the hip muscles with difficulty in rising from the floor or chair and in climbing stairs. This is accompanied by enlargement of the calf muscles, which are infiltrated by fat and fibrous tissue (pseudohypertrophy). Weakness of the muscles of the upper arms and shoulder muscles follows.

Becker's muscular dystrophy is also characterized by calf pseudohypertrophy but is much more slowly progressive.

Myotonic dystrophy is very slowly progressive and affects the muscles of the face, neck, and hands. It usually begins in early adulthood. In addition to progressive weakness and wasting of the affected muscles, these individuals also exhibit myotonia, that is, a delayed relaxation of a muscle after forceful contraction. Mental retardation, frontal balding, cataracts, and gonadal degeneration are common.

Treatment remains largely symptomatic. See also Muscular system disorders.

Definition

Muscular dystrophy is the name for a group of inherited disorders in which strength and muscle bulk gradually decline. Nine types of muscular dystrophies are generally recognized.

Description

The muscular dystrophies include:

• Duchenne muscular dystrophy (DMD), which affects young boys, causing progressive muscle weakness, usually beginning in the legs. It is the most severe form of muscular dystrophy.
• Becker muscular dystrophy (BMD), which affects older boys and young men, following a milder course than DMD
• Emery-Dreifuss muscular dystrophy (EDMD), which affects young boys, causing contractures and weakness in the calves, weakness in the shoulders and upper arms, and problems in the way electrical impulses travel through the heart to make it beat (heart conduction defects). Female carriers of EDMD are at risk for heart block.
• Limb-girdle muscular dystrophy (LGMD), which begins in late childhood to early adulthood and affects both men and women, causing weakness in the muscles around the hips and shoulders. It is the most variable of the muscular dystrophies, and there are as of 2004 several different forms of the disease recognized. Many people with suspected LGMD have probably been misdiagnosed in the past; therefore, the prevalence of the disease is difficult to estimate.
• Facioscapulohumeral muscular dystrophy (FSH), also known as Landouzy-Dejerine disease, which begins in late childhood to early adulthood and affects both men and women, causing weakness in the muscles of the face, shoulders, and upper arms. The hips and legs may also be affected.
• Myotonic dystrophy, also known as Steinert's disease, which affects both men and women, causing generalized weakness first seen in the face, feet, and hands. It is accompanied by the inability to relax the affected muscles (myotonia). Symptoms may begin any time from birth through adulthood.
• Oculopharyngeal muscular dystrophy (OPMD), which affects adults of both sexes, causing weakness in the eye muscles and throat
• Distal muscular dystrophy (DD), which begins in middle age or later, causing weakness in the muscles of the feet and hands
• Congenital muscular dystrophy (CMD), which is present from birth, results in generalized weakness, and usually progresses slowly. A subtype, called Fukuyama CMD, also involves mental retardation. Both are rare.

Demographics

DMD occurs in about one in 3,500 male births and affects approximately 8,000 boys and young men in the United States. A milder form occurs in very few female carriers.

BMD occurs in about one in 30,000 male births.

Fewer than 300 cases of EDMD have been identified.

The number of people affected with LGMD in the United States may be in the low thousands.

FSH occurs in about one out of every 20,000 people and affects approximately 13,000 people in the United States.

Myotonic dystrophy is the most common form of muscular dystrophy, affecting more than 30,000 people in the United States.

OPMD is most common among French Canadian families in Quebec and in Spanish-American families in the southwestern United States.

DD is most common in Sweden and rare in other parts of the world.

Fukuyama CMD is most common in Japan.

Causes and Symptoms

Causes

Several of the muscular dystrophies, including DMD, BMD, CMD, and most forms of LGMD, are due to defects in the genes for a complex of muscle proteins. This complex spans the muscle cell membrane to unite a fibrous network on the interior of the cell with a fibrous network on the outside. As of 2004 the theory was that by linking these two networks, the complex acts as a "shock absorber," redistributing and evening out the forces generated by contraction of the muscle, thereby preventing rupture of the muscle membrane. Defects in the proteins of the complex lead to deterioration of the muscle. Symptoms of these diseases set in as the muscle gradually exhausts its ability to repair itself. Both DMD and BMD are caused by flaws in the gene for the protein called dystrophin. The flaw leading to DMD prevents the formation of any dystrophin, while that of BMD allows some protein to be made, accounting for the differences in severity and onset between the two diseases. Differences among the other diseases in the muscles involved and the ages of onset are less easily explained.

The causes of the other muscular dystrophies are not as well understood:

• One form of LGMD is caused by defects in the gene for a muscle enzyme, calpain. The relationship between this defect and the symptoms of the disease is unclear.
• EDMD is due to a defect in the gene for a protein called emerin, which is found in the membrane of a cell's nucleus, but whose exact function is unknown.
• Myotonic dystrophy is linked to gene defects for a protein that may control the flow of charged particles within muscle cells. This gene defect is called a triple repeat, meaning it contains extra triplets of DNA code. It is possible that this mutation affects nearby genes as well, and that the widespread symptoms of myotonic dystrophy are due to a range of genetic disruptions.
• The gene for OPMD appears to also be mutated with a triple repeat. The function of the affected protein may involve translation of genetic messages in a cell's nucleus.
• The cause of FSH is unknown. The genetic region responsible for it has been localized on its chromosome, however.
• The gene responsible for DD has not yet been found.

Genetics and Patterns of Inheritance

The muscular dystrophies are genetic diseases, meaning they are caused by defects in genes. Genes, which are linked together on chromosomes, have two functions. They code for the production of proteins, and they are the material of inheritance. Parents pass along genes to their children, providing them with a complete set of instructions for making their own proteins.

Because both parents contribute genetic material to their offspring, each child carries two copies of almost every gene, one from each parent. For some diseases to occur, both copies must be flawed. Such diseases are called autosomal recessive diseases. Some forms of LGMD and DD exhibit this pattern of inheritance, as does CMD. A person with only one flawed copy, called a carrier, will not have the disease but may pass the flawed gene on to children. When two carriers have children, the chances of having a child with the disease is one in four for each pregnancy.

Other diseases occur when only one flawed gene copy is present. Such diseases are called autosomal dominant diseases. Other forms of LGMD exhibit this pattern of inheritance, as do DM, FSH, OPMD, and some forms of DD. When a person affected by the disease has a child with someone not affected, the chances of having an affected child is one in two.

Because of chromosomal differences between the sexes, some genes are not present in two copies. The chromosomes that determine whether a person is male or female are called the X and Y chromosomes. A person with two X chromosomes is female, while a person with one X and one Y is male. While the X chromosome carries many genes, the Y chromosome carries almost none. Therefore, a male has only one copy of each gene on the X chromosome, and if it is flawed, he will have the disease that defect causes. Such diseases are said to be X-linked. X-linked diseases include DMD, BMD, and EDMD. Women are not usually affected by X-linked diseases, since they will likely have one unaffected copy between the two chromosomes. Some female carriers of DMD suffer a mild form of the disease, probably because their one unaffected gene copy is shut down in some of their cells.

Women carriers of X-linked diseases have a one-in-two chance of passing the flawed gene on to each child born. Daughters who inherit the disease gene are carriers. A son born without the disease gene is free of the disease and cannot pass it on to his children. A son born with the defect has the disease. He will pass the flawed gene on to each of his daughters, who will then be carriers, but to none of his sons (because they inherit his Y chromosome).

Not all genetic flaws are inherited. As many as one-third of the cases of DMD are due to new mutations that arise during egg formation in the mother. New mutations are less common in other forms of muscular dystrophy.

Symptoms

All of the muscular dystrophies are marked by muscle weakness as the major symptom. The distribution of symptoms, age of onset, and progression differ significantly. Pain is sometimes a symptom of each, usually due to the effects of weakness on joint position.

DMD. A boy with Duchenne muscular dystrophy usually begins to show symptoms as a preschooler. The legs are affected first, making walking difficult and causing balance problems. Most affected persons walk three to six months later than expected and have difficulty running. Later on, the boy with DMD will push his hands against his knees to rise to a standing position, to compensate for leg weakness. About the same time, his calves will begin to swell, though with fibrous tissue rather than with muscle and feel firm and rubbery; this condition gives DMD one of its alternate names, pseudohypertrophic muscular dystrophy. The boy will widen his stance to maintain balance and walk with a waddling gait to advance his weakened legs. Contractures (permanent muscle tightening) usually begin by age five or six, most severely in the calf muscles. This pulls the foot down and back, forcing the boy to walk on tip-toes, called equinus, and further decreases balance. Frequent falls and broken bones are common beginning at this age. Climbing stairs and rising unaided may become impossible by age nine or ten, and most boys use a wheelchair for mobility by the age of 12. Weakening of the trunk muscles around this age often leads to scoliosis (a side-to-side spine curvature) and kyphosis (a front-to-back curvature).

The most serious weakness of DMD is weakness of the diaphragm, the sheet of muscles at the top of the abdomen that perform the main work of breathing and coughing. Diaphragm weakness leads to reduced energy and stamina and increased lung infection because of the inability to cough effectively. Young men with DMD often live into their twenties and beyond, provided they have mechanical ventilation assistance and good respiratory hygiene.

About one third of boys with DMD experience specific learning disabilities, including trouble learning by ear rather than by sight and trouble paying attention to long lists of instructions. Individualized educational programs usually compensate well for these disabilities.

BMD. The symptoms of BMD usually appear in late childhood to early adulthood. Though the progression of symptoms may parallel that of DMD, the symptoms are usually milder, and the course more variable. The same pattern of leg weakness, unsteadiness, and contractures occurs later for the young man with BMD, often allowing independent walking into the twenties or early thirties. Scoliosis may occur but is usually milder and progresses more slowly. Heart muscle disease (cardiomyopathy) occurs more commonly in BMD. Problems may include irregular heartbeats (arrhythmias) and congestive heart failure. Symptoms may include fatigue, shortness of breath, chest pain, and dizziness. Respiratory weakness also occurs and may lead to the need for mechanical ventilation.

EDMD. This type of muscular dystrophy usually begins in early childhood, often with contractures preceding muscle weakness. Weakness affects the shoulder and upper arm originally, along with the calf muscles, leading to foot-drop. Most men with EDMD survive into middle age, although a defect in the heart's rhythm (heart block) may be fatal if not treated with a pacemaker.

LGMD. While there are at least six genes that cause the various types of LGMD, two major clinical forms of LGMD are usually recognized. A severe childhood form is similar in appearance to DMD but is inherited as an autosomal recessive trait. Symptoms of adult-onset LGMD usually appear in a person's teens or twenties and are marked by progressive weakness and wasting of the muscles closest to the trunk. Contractures may occur, and the ability to walk is usually lost about 20 years after onset. Some people with LGMD develop respiratory weakness that requires use of a ventilator. Lifespan may be somewhat shortened. (Autosomal dominant forms usually occur later in life and progress relatively slowly.)

FSH. FSH varies in its severity and age of onset, even among members of the same family. Symptoms most commonly begin in the teens or early twenties, though infant or childhood onset is possible. Symptoms tend to be more severe in those with earlier onset. The disease is named for the regions of the body most severely affected by the disease: muscles of the face (facio-), shoulders (scapulo-), and upper arms (humeral). Hips and legs may be affected as well. Children with FSH often develop partial or complete deafness.

The first symptom noticed is often difficulty lifting objects above the shoulders. The weakness may be greater on one side than the other. Shoulder weakness also causes the shoulder blades to jut backward, called scapular winging. Muscles in the upper arm often lose bulk sooner than those of the forearm, giving a "Popeye" appearance to the arms. Facial weakness may lead to loss of facial expression, difficulty closing the eyes completely, and inability to drink through a straw, blow up a balloon, or whistle. A person with FSH may not develop strong facial wrinkles. Contracture of the calf muscles may cause foot-drop, leading to frequent tripping over curbs or rough spots. People with earlier onset often require a wheelchair for mobility, while those with later onset rarely do.

MYOTONIC DYSTROPHY. Symptoms of myotonic dystrophy include facial weakness and a slack jaw, drooping eyelids (ptosis), and muscle wasting in the forearms and calves. A person with this dystrophy has difficulty relaxing his grasp, especially if the object is cold. Myotonic dystrophy affects heart muscle, causing arrhythmias and heart block, and the muscles of the digestive system, leading to motility disorders and constipation. Other body systems are affected as well: myotonic dystrophy may cause cataracts, retinal degeneration, low IQ, frontal balding, skin disorders, testicular atrophy, sleep apnea, and insulin resistance. An increased need or desire for sleep is common, as is diminished motivation. Severe disability affects most people with this type of dystrophy within 20 years of onset, although most do not require a wheelchair even late in life.

OPMD. OPMD usually begins in a person's thirties or forties, with weakness in the muscles controlling the eyes and throat. Symptoms include drooping eyelids, difficulty swallowing (dysphagia), and weakness progresses to other muscles of the face, neck, and occasionally the upper limbs. Swallowing difficulty may cause aspiration or the introduction of food or saliva into the airways. Pneumonia may follow.

DD. DD usually begins in the twenties or thirties with weakness in the hands, forearms, and lower legs.

Difficulty with fine movements such as typing or fastening buttons may be the first symptoms. Symptoms progress slowly, and the disease usually does not affect life span.

CMD. CMD is marked by severe muscle weakness from birth, with infants displaying "floppiness" and very little voluntary movement. Nonetheless, a child with CMD may learn to walk, either with or without some assistive device, and live into young adulthood or beyond. In contrast, children with Fukuyama CMD are rarely able to walk and have severe mental retardation. Most children with this type of CMD die in childhood.

When to Call the Doctor

A doctor should be consulted whenever muscle development is thought to be abnormal or slow.

Diagnosis

Diagnosis of muscular dystrophy involves a careful medical history and a thorough physical exam to determine the distribution of symptoms and to rule out other causes. Family history may give important clues, since all the muscular dystrophies are genetic conditions (though no family history will be evident in the event of new mutations).

Lab tests may include the following:

• Blood level of the muscle enzyme creatine kinase (CK). CK levels rise in the blood due to muscle damage and may be seen in some conditions even before symptoms appear.
• Muscle biopsy, in which a small piece of muscle tissue is removed for microscopic examination. Changes in the structure of muscle cells and presence of fibrous tissue or other aberrant structures are characteristic of different forms of muscular dystrophy. The muscle tissue can also be stained to detect the presence or absence of particular proteins, including dystrophin.
• Electromyogram (EMG). EMG is used to examine the response of the muscles to stimulation. Decreased response is seen in muscular dystrophy. Other characteristic changes are seen in DM.
• Genetic tests. Several of the muscular dystrophies can be positively identified by testing for the presence of the mutated gene involved. Accurate genetic tests are available for DMD, BMD, DM, several forms of LGMD, and EDMD.
• Other specific tests as necessary. For EDMD and BMD, for example, an electrocardiogram may be needed to test heart function, and hearing tests are performed for children with FSH.

For most forms of muscular dystrophy, accurate diagnosis is not difficult when done by someone familiar with the range of diseases. There are exceptions, however. Even with a muscle biopsy, it may be difficult to distinguish between FSH and another muscle disease, polymyositis. Childhood-onset LGMD is often mistaken for the much more common DMD, especially when it occurs in boys. BMD with an early onset appears very similar to DMD, and a muscle biopsy may be needed to accurately distinguish them. The muscular dystrophies may be confused with diseases involving the motor neurons, such as spinal muscular atrophy; diseases of the neuromuscular junction, such as myasthenia gravis; and other muscle diseases, as all involve generalized weakening of varying distribution.

Treatment

Drugs

As of 2004 there were no cures for any of the muscular dystrophies. Prednisone, a corticosteroid, has been shown to delay the progression of DMD somewhat, for reasons that as of 2004 are still unclear. Prednisone is also prescribed for BMD.

Treatment of muscular dystrophy is mainly directed at preventing the complications of weakness, including decreased mobility and dexterity, contractures, scoliosis, heart defects, and respiratory insufficiency.

Physical Therapy

Physical therapy, in particular regular stretching, is used to maintain the range of motion of affected muscles and to prevent or delay contractures. Braces are used as well, especially on the ankles and feet to prevent equinus. Full-leg braces may be used in DMD to prolong the period of independent walking. Strengthening other muscle groups to compensate for weakness may be possible if the affected muscles are few and isolated, as in the earlier stages of the milder muscular dystrophies. Regular, nonstrenuous exercise helps maintain general good health. Strenuous exercise is usually not recommended, since it may damage muscles further.

Surgery

When contractures become more pronounced, tenotomy surgery may be performed. In this operation, the tendon of the contractured muscle is cut, and the limb is braced in its normal resting position while the tendon regrows. In FSH, surgical fixation of the scapula can help compensate for shoulder weakness. For a person with OPMD, surgical lifting of the eyelids may help compensate for weakened muscular control. For a person with DM, sleep apnea may be treated surgically to maintain an open airway. Scoliosis surgery is often needed in DMD but much less often in other muscular dystrophies. Surgery is recommended at a much lower degree of curvature for DMD than for scoliosis due to other conditions, since the decline in respiratory function in DMD makes surgery at a later time dangerous. In this surgery, the vertebrae are fused together to maintain the spine in the upright position. Steel rods are inserted at the time of operation to keep the spine rigid while the bones grow together.

When any type of surgery is performed in people with muscular dystrophy, anesthesia must be carefully selected. People with MD are susceptible to a severe reaction, known as malignant hyperthermia, when given halothane anesthetic.

Occupational Therapy

The occupational therapist suggests techniques and tools to compensate for the loss of strength and dexterity. Strategies may include modifications in the home, adaptive utensils and dressing aids, compensatory movements and positioning, wheelchair accessories, or communication aids.

Nutrition

Good nutrition helps to promote general health in all the muscular dystrophies. No special diet or supplement has as of 2004 been shown to be of use in any of the conditions. The weakness in the throat muscles seen especially in OPMD and later DMD may necessitate the use of a gastrostomy tube, inserted in the stomach to provide nutrition directly.

Cardiac Care

The arrhythmias of EDMD and BMD may be treatable with antiarrhythmia drugs such as mexiletine or nifedipine. A pacemaker may be implanted if these do not provide adequate control. Heart transplants are increasingly common for men with BMD.

Respiratory Care

People who develop weakness of the diaphragm or other ventilatory muscles may require a mechanical ventilator to continue breathing deeply enough. Air may be administered through a nasal mask or mouthpiece or through a tracheostomy tube, which is inserted through a surgical incision through the neck and into the windpipe. Most people with muscular dystrophy do not need a tracheostomy, although some may prefer it to continual use of a mask or mouthpiece. Supplemental oxygen is not needed. Good hygiene of the lungs is critical for health and long-term survival of a person with weakened ventilatory muscles. Assisted cough techniques provide the strength needed to clear the airways of secretions; an assisted cough machine is also available and provides excellent results.

Experimental Treatments

Two experimental procedures aiming to cure DMD have attracted a great deal of attention. In myoblast transfer, millions of immature muscle cells are injected into an affected muscle. The goal of the treatment is to promote the growth of the injected cells, replacing the defective host cells with healthy new ones. Despite continued claims to the contrary by a very few researchers, this procedure is widely judged a failure.

Gene therapy introduces good copies of the dystrophin gene into muscle cells. The goal is to allow the existing muscle cells to use the new gene to produce the dystrophin it cannot make with its flawed gene. Problems have included immune rejection of the virus used to introduce the gene, loss of gene function after several weeks, and an inability to get the gene to enough cells to make a functional difference in the affected muscle. Nonetheless, after a number of years of refining the techniques in mice, researchers began human trials in 1998. These trials are ongoing.

Prognosis

The expected life span for a male with DMD has increased significantly since the 1970s. Most young men live into their early or mid-twenties. Respiratory infections become an increasing problem as their breathing becomes weaker, and these infections are usually the cause of death.

The course of the other muscular dystrophies is more variable; expected life spans and degrees of disability are hard to predict but may be related to age of onset and initial symptoms. Prediction is made more difficult because, as new genes are discovered, it becomes clear that several of the dystrophies are not uniform disorders but rather symptom groups caused by different genes.

People with dystrophies with significant heart involvement (BMD, EDMD, Myotonic dystrophy) may nonetheless have almost normal life spans, provided that cardiac complications are monitored and treated aggressively. The respiratory involvement of BMD and LGMD similarly require careful and prompt treatment.

Prevention

As of 2004 there was no way to prevent any of the muscular dystrophies in a person who has the genes responsible for these disorders. Accurate genetic tests, including prenatal tests, are available for some of the muscular dystrophies. Results of these tests may be useful for purposes of family planning.

Nutritional Concerns

There is no known link between nutrition and the onset of muscular dystrophy.

Parental Concerns

Prospective parents with first-degree relatives (parents, siblings, or other children) who have been diagnosed with muscular dystrophy should consider including counseling in their family planning process.

Resources

Books

Barohn, Richard J. "Muscle Diseases." In Cecil Textbook ofMedicine, 22nd ed. Edited by Lee Goldman et al. Philadelphia: Saunders, 2003, pp. 2387–99.

Brown, Robert H., and Jerry R. Mendell. "Muscular Dystrophies and Other Muscle Diseases." In Harrison's Principles of Internal Medicine, 15th ed. Edited by Eugene Braunwald et al. New York: McGraw-Hill, 2001, pp. 2529–40.

Emery, Alan E. Muscular Dystrophies. Cary, NC: Oxford University Press, 2003.

Muscular Dystrophy: A Medical Dictionary, Bibliography, andAnnotated Research Guide to Internet References. San Diego, CA: Icon Health Publications, 2003.

Sarnat, Harvey B. "Muscular Dystrophies." In NelsonTextbook of Pediatrics, 17th ed. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2003, pp. 2060–9.

Periodicals

Cossu, G., and M. Sampaolesi. "New therapies for muscular dystrophy: cautious optimism." Trends in Molecular Medicine 10, no. 10 (2004): 516–20.

Rando, T. A. "Artificial sweeteners—enhancing glycosylation to treat muscular dystrophies." New England Journal of Medicine 351, no. 12 (2004): 1254–6.

Organizations

American Academy of Physical Medicine and Rehabilitation. One IBM Plaza, Suite 2500, Chicago, IL 60611–3604. Web site: www.aapmr.org/.

Muscular Dystrophy Association. National Headquarters, 3300 E. Sunrise Drive, Tucson, AZ 85718. Web site: www.mdausa.org//p

Web Sites

"Muscular Dystrophies." Merck Manual. Available online at www.merck.com/mrkshared/mmanual/section14/chapter184/184a.jsp (accessed January 7, 2005).

"Muscular Dystrophy." Milton S. Hershey Medical CenterSchool of Medicine. Available online at www.hmc.psu.edu/healthinfo/m/musculardystrophy.htm (accessed January 7, 2005).

[Article by: L. Fleming Fallon, Jr., MD, DrPH]

Muscular dystrophies (MDs) are a group of disorders that share three characteristics: They are inherited, they cause progressive weakness and muscle wasting, and the primary defect is localized to skeletal muscle, sparing the nerves. Although selected limb muscles develop some degree of weakness in all dystrophies, to distinguish among the different types, it is critical to know the mode of inheritance, the age of onset, and whether muscles other than limb muscles are also affected. For example, some dystrophies additionally affect eye and lip closure; another type affects eye movement ability, as well as swallowing and speech.

More than thirty types of MDs are now recognized. Three of the more prevalent forms—Duchenne, myotonic, and limb-girdle dystrophies—will be discussed from the standpoint of the presenting symptoms, age of onset, inheritance pattern, causative genes, and the availability of prenatal and presymptomatic molecular testing.

Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with a worldwide occurrence of one in four thousand newborn males, with approximately one-third of the cases arising from new mutations. DMD was named after the French neurologist Duchenne de Boulogne, who described the disorder in 1861. Becker muscular dystrophy (BMD), named after Peter Becker, a German geneticist who first described it in the mid-1950s, is a disorder that is very similar to DMD but has a much milder course. In 1983 these disorders were first shown to be located on the short arm of the X chromosome. The disorders are now known to be allelic, meaning an alternate form of the DMD gene causes BMD.

Because DMD is X-linked, almost all cases occur in males. Boys with DMD are normal at birth, and their early motor milestones occur at normal times. The manifestations of DMD are frequently apparent from the time they begin to walk, due to the developing weakness of the hip-girdle and upper-leg muscles. Their gait is unsteady and clumsy, resulting in frequent falls. If running is attempted, it is slow and waddling. The calf muscles often are enlarged enough to be termed "hypertrophic," implying that these children are muscular and strong. In reality calf pseudo hypertrophy is present: When the calves are examined microscopically, the amount of muscle tissue is markedly reduced, having been replaced by fat and fibrous tissue.

As the disorder progresses, the Achilles tendons tighten, causing toe-walking, which further compromises patients' gait and balance. Stair-climbing, rising from a fall, and even walking on level ground becomes more arduous. Even if they undergo Achilles tendon lengthening surgery or use leg braces, virtually all DMD boys require a wheelchair for mobility before the age of thirteen. Weakening of the muscles of the upper extremities and neck and of the respiratory muscles occurs in parallel to that of the lower extremities, although at a slower rate. By some time in their twenties, if not before, nearly all DMD patients will die, often due to an overwhelming respiratory infection resulting in respiratory failure, cardiac arrest, or both.

The causative gene for DMD (named dystrophin) and the protein product (also named dystrophin) were identified in 1986. Dystrophin is found on the inner side of the membrane that surrounds skeletal muscle fibers (the sarcolemma). It is usually absent or severely deficient in DMD boys, and this causes the sarcolemma to weaken and develop tears, allowing excess calcium to enter the muscle fiber. This eventually leads to the death of muscle fibers, and, when a sufficient number of fibers are involved, muscle weakness results.

The dystrophin gene is the largest known human gene, encompassing two thousand kilobases (two million bases) of genomic DNA. In 55 percent to 65 percent of DMD or BMD cases, large deletions of the dystrophin gene can be found. Duplications within the gene account for about 5 percent of cases. DNA testing, available through a number of commercial laboratories in the United States, is based on the identification of these large deletions and duplications. DNA tests can confirm a diagnosis of DMD or BMD, and they can be used for accurate carrier or prenatal testing.

Myotonic Muscular Dystrophy

Myotonic muscular dystrophy (DM, or dystrophia myotonica) is the most common adult-onset muscular dystrophy, having a frequency of one per twenty thousand persons in the general population. Myotonia, the delayed relaxation of a voluntary muscle after it is contracted, and muscle weakness are the hallmarks of the disorder. For example, a person with DM using a hammer will not immediately be able to release his grip on the handle when finished. It is an autosomal dominant disorder, but there is great variability in the disorder's severity and in the number of manifestations it leads to.

A unique feature of this dystrophy is a genetic phenomenon called pleiotropy, or multisystem involvement, despite the single genetic defect. The potential involvement includes multiple organs and organ systems other than skeletal muscle, including the cardiac, respiratory, gastrointestinal, central nervous, endocrine, and dermatologic systems, as well as bone or eyes. A congenital variety occurs in which infants are born floppy, often require respiratory assistance, have extremity deformities, and are both physically and mentally retarded.

Patients often initially complain of a loss of hand strength (they have difficulty twisting off caps from bottles, for example) or of tripping while walking or climbing stairs, due to the weakness of muscles that extend the feet and toes. Weakness may progress to involve the shoulder and hip girdles and, in some cases, is severe enough to necessitate the use of a wheel-chair. Droopy eyelids, wasting of facial and neck muscles, and frontal balding frequently occur, producing atypical facial appearance.

The gene for DM is a protein kinase gene (known as DMPK) and is located on the long arm of chromosome 19. The disorder arises from a repeated sequence of three nucleotides—cytosine (C), thymine (T), and gua-nine (G)—in the gene. Individuals without DM have C-T-G repeats that contain between 5 and 37 iterations of the triplets. By contrast, repeats that are between 40 and 170 iterations long are found in the mild phenotype, repeats between 100 and 1,000 iterations are found in the "classic pheno-type," and repeats of between 500 and 3,000 are found in the congenital phenotype. A number of laboratories in the United States perform this triplet repeat assay for diagnostic, prenatal, and presymptomatic testing.

Limb-Girdle Muscular Dystrophy

Limb-girdle muscular dystrophy (LGMD) has been described both as a heterogeneous group of disorders and as a diagnosis of exclusion. Any patient who has weakness of the shoulder and hip-girdle muscles and who otherwise has been excluded from the other MDs will be diagnosed with LGMD. Using the patterns of inheritance that exist within LGMD, a classification system has been created to simplify the heterogeneity: Both autosomal dominant (LGMD1) and recessive families (LGMD2) are well recognized. The number of LGMD genes that have already been identified has further improved the classification.

The frequency of LGMD in the general population is reported to be one in twenty-five thousand. The age at onset may vary widely. In some individuals, onset is in early childhood and in others it occurs in the forties and fifties, but most commonly it occurs in the teens to early adulthood. The characteristic pattern of muscle involvement is symmetric weakness, beginning initially in the hip and shoulder girdle, but usually noticed in the hips before the shoulders. Thus slowness in running, difficulty rising from a low seat, and difficulty ascending stairs are all common complaints from affected individuals. As LGMD progresses, it will involve upper-leg and arm muscles and may eventually affect the muscles that extend the feet and wrists. Lower-extremity weakness may become severe enough to require a wheelchair.

Among the LGMD1 types, five have chromosomal linkages, but only in one is the protein product of the gene known. LGMD2 is better characterized, with nine chromosomal localizations, five with known proteins. Almost all these proteins are membrane-associated proteins (just as dystrophin is). When they are abnormal in structure or deficient in quantity, they affect the stability of the muscle membrane, resulting in the same pathological process that was described for DMD. Commercial testing in the United States is only available for some of the LGMD2 types and is performed using muscle tissue.

Treatment of the Muscular Dystrophies

As of mid-2002, gene therapy treatment of LGMD was tried in a very small number of patients. These early experiments delivered a functional gene to a very small muscle in the foot and were designed to test the long-term safety and effectiveness of the treatment. Gene therapy for DMD is much more problematic, because of the immense size of the gene and the distribution throughout the body that would be required for effective treatment. Drug treatment with prednisone or other corticosteroids is being used, although at best this provides another six to twelve months of mobility before a wheelchair becomes necessary. There are no effective treatments for myotonic dystrophy as of 2002, although research continues in many laboratories worldwide.

Bibliography

Emery, Alan E. H., ed. Neuromuscular Disorders: Clinical and Molecular Genetics. Chichester, U.K.: John Wiley & Sons, 1998.

———. Muscular Dystrophy, The Facts. Oxford, U.K.: Oxford University Press, 2000.

Hoffman, Eric P. "Muscular Dystrophy: Identification and Use of Genes for Diagnostics and Therapeutics." Archives of Pathology and Laboratory Medicine 123 (1999): 1050-1052.

Internet Resource

Muscular Dystrophy Association. http://www.mdausa.org.

—Jeffrey M. Stajich

A disease in which there is a progressive wasting of muscle.

From our Archives: Today's Highlights, September 6, 2010

A hereditary disease in which the muscles progressively waste away. The disease can be potentially treated through gene therapy.

A group of genetically transmitted diseases characterized by progressive atrophy of symmetric groups of skeletal muscles without evidence of involvement or degeneration of neural tissue. In all forms of muscular dystrophy there is an insidious loss of strength with increasing disability and deformity. Serum creatine phosphokinase is increased in affected individuals and acts as a diagnostic aid. Diagnosis is confirmed by muscle biopsy, electromyography, and genetic pedigree.

• Diseases and Infestations - muscular dystrophy: inherited muscle disease marked by degeneration of muscle fiber

Muscular dystrophy
Classification and external resources
In affected muscle the tissue becomes disorganized and the concentration of dystrophin (green) is greatly reduced.
ICD-10	G71.0
ICD-9	359.0-359.1
MedlinePlus	001190
eMedicine	orthoped/418
MeSH	D009136

Muscular dystrophy (MD) is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion.^[1][2] Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.^[3]

In the 1860s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of thirteen boys with the most common and severe form of the disease, which now carries his name—Duchenne muscular dystrophy.

It soon became evident that the disease had more than one form. The other major forms are Becker, limb-girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss muscular dystrophy.^[4] These diseases predominately affect males, although females may be carriers of the disease gene. Most types of MD are multi-system disorders with manifestations in body systems including the heart, gastrointestinal system, nervous system, endocrine glands, eyes and brain.^[4]

Apart from the nine major types of muscular dystrophy listed above, several MD-like conditions have also been identified. Normal intellectual, behavioral, bowel and sexual function is noticed in individuals with other forms of MD and MD-like conditions.^[5][6] MD-affected individuals with susceptible intellectual impairment are diagnosed through molecular characteristics but not through problems associated with disability.^[7] However, a third of patients who are severely affected with DMD may have cognitive impairment, behavioral, vision and speech problems.^[8][9]

Contents 1 Signs and symptoms 2 Cause 3 Diagnosis 4 Management 5 Prognosis 6 Types 7 Research funding 8 See also 9 References 10 External links

Signs and symptoms

• Progressive muscular wasting
• Poor balance
• Drooping eyelids
• Atrophy
• Scoliosis (curvature of the spine and the back)
• Inability to walk
• Frequent falls
• Waddling gait
• Calf deformation
• Limited range of movement
• Respiratory difficulty
• Joint contractures
• Cardiomyopathy
• Arrhythmias
• Muscle Spasms

Cause

These conditions are generally inherited, and the different muscular dystrophies follow various inheritance patterns. However, mutations of the dystrophin gene and nutritional defects (with no genetics history) at the prenatal stage are also possible in about 33% of people affected by DMD.^[10] The main cause of the Duchenne and Becker types of muscular dystrophy is the muscle tissue's cytoskeletal impairment to properly create the functional protein dystrophin and dystrophin-associated protein complex.

Dystrophin protein is found in muscle fibre membrane, acting like a spring. It joins the membrane actin filaments. The protein is rod shaped around 150 nm in length, 3684 amino acids long, 427 kDa molecule weight. It is hydrophobic (repels water). Conformation is alpha-helical, allowing protein to act as a shock absorber, preventing overstress. Dystrophin links actin (cytoskeleton) and dystroglycans of the muscle cell plasma membrane, known as the sarcolemma (extracellular). Dystrophin functions in two ways; mechanical stabilisation and regulated calcium levels.

Diagnosis

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase (CpK3), electromyography, electrocardiography and DNA analysis.

A physical examination and the patient's medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.

Often, there is a loss of muscle mass (wasting), which may be hard to see because some types of muscular dystrophy cause a build up of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.

Management

There is no known cure for muscular dystrophy, although significant headway is being made with antisense oligonucleotides.^[11] Physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis), speech therapy and orthopedic instruments (e.g., wheelchairs and standing frames) may be helpful. Inactivity (such as bed rest, sitting for long periods) and bodybuilding efforts to increase myofibrillar hypertrophy can worsen the disease.

There is no specific treatment for any of the forms of muscular dystrophy. Physiotherapy, aerobic exercise, low intensity anabolic steroids, prednisone supplements may help to prevent contractures and maintain muscle tone. Orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine, phenytoin, or mexiletine, but no actual long term treatment has been found.

Occupational therapy assists the individual with MD in engaging in his/her activities of daily living (self-feeding, self-care activities, etc.) and leisure activities at the most independent level possible. This may be achieved with use of adaptive equipment or the use of energy conservation techniques. Occupational therapy may implement changes to a person's environment, both at home or work, to increase the individual's function and accessibility. Occupational therapists also address psychosocial changes and cognitive decline which may accompany MD, as well as provide support and education about the disease to the family and individual.^[12]

High dietary intake of lean meat, sea food, pulses, milk, egg, olive oil, leafy vegetables, bell pepper, fiber, wheat, antioxidants, fruits like blueberry, cherry etc. is advised. Decreased intake of carbohydrates, fats, dairy foods such as butter and milk, and caffeinated and alcoholic beverages is advised.^[13]

Diagnosis, neurology, GI-nutrition, respiratory care, cardiac care, orthopedics, psychosocial, rehabilitation, and oral care form the integral part of disease management, all through the patient's life span.

Prognosis

The prognosis for people with muscular dystrophy varies according to the type and progression of the disorder. Some cases may be mild and progress very slowly over a normal lifespan, while others produce severe muscle weakness, functional disability, and loss of the ability to walk. Some children with muscular dystrophy die in infancy while others live into adulthood with only moderate disability. The muscles affected vary, but can be around the pelvis, shoulder, face or elsewhere. Muscular dystrophy can affect adults, but the more severe forms tend to occur in early childhood.

Types

Type	OMIM	Gene	Description
Becker's muscular dystrophy	300376	DMD	Becker muscular dystrophy (BMD) is a less severe variant of Duchenne muscular dystrophy and is caused by the production of a truncated, but partially functional form of dystrophin.[4] Survival is usually into old age.[14] Affects only boys (with extremely rare exceptions)
Congenital muscular dystrophy	Multiple	Multiple	Age at onset: birth; symptoms include general muscle weakness and possible joint deformities; disease progresses slowly; shortened life span.[15] Congenital muscular dystrophy includes several disorders with a range of symptoms. Muscle degeneration may be mild or severe. Problems may be restricted to skeletal muscle, or muscle degeneration may be paired with effects on the brain and other organ systems. A number of the forms of the congenital muscular dystrophies are caused by defects in proteins that are thought to have some relationship to the dystrophin-glycoprotein complex and to the connections between muscle cells and their surrounding cellular structure. Some forms of congenital muscular dystrophy show severe brain malformations, such as lissencephaly and hydrocephalus.[4]
Duchenne muscular dystrophy	310200	DMD	Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy, it generally affects only boys (with extremely rare exceptions), becoming clinically evident when a child begins walking. By age 10, the child may need braces for walking and by age 12, most patients are confined to a wheelchair.[16] Patients usually die around age 25, but this depends from person to person.[16] In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. The amount of dystrophin correlates with the severity of the disease (i.e. the less dystrophin present, the more severe the phenotype). Since the gene is on the X chromosome, this disorder affects primarily males, and females who are carriers have milder symptoms. Sporadic mutations in this gene occur frequently, accounting for a third of cases. The remaining two-thirds of cases are inherited in a recessive pattern. Dystrophin is part of a complex structure involving several other protein components. The "dystrophin-glycoprotein complex" helps anchor the structural skeleton (cytoskeleton) within the muscle cells, through the outer membrane (sarcolemma) of each cell, to the tissue framework (extracellular matrix) that surrounds each cell. Due to defects in this assembly, contraction of the muscle leads to disruption of the outer membrane of the muscle cells and eventual weakening and wasting of the muscle.[4]
Distal muscular dystrophy	254130	DYSF	Distal muscular dystrophies' age at onset: 20 to 60 years; symptoms include weakness and wasting of muscles of the hands, forearms, and lower legs; progress is slow and not life-threatening.[14] Miyoshi myopathy, one of the distal muscular dystrophies, causes initial weakness in the calf muscles, and is caused by defects in the same gene responsible for one form of LGMD (Limb Girdle Muscular Dystrophy).[4]
Emery-Dreifuss muscular dystrophy	310300, 181350	EMD, LMNA	Emery-Dreifuss Muscular Dystrophy patients normally present in childhood and the early teenage years with contractures. Clinical signs include muscle weakness and wasting, starting in the distal limb muscles and progressing to involve the limb-girdle muscles. Most patients also suffer from cardiac conduction defects and arrhythmias which, if left untreated, increase the risk of stroke and sudden death. There are three subtypes of Emery-Dreifuss Muscular Dystrophy, distinguishable by their pattern of inheritance: X-Linked, autosomal dominant and autosomal recessive. The X-linked form is the most common. Each type varies in prevalence and symptoms. The disease is caused by mutations in the LMNA gene, or more commonly, the EMD gene. Both genes encode for protein componenets of the nuclear envelope. However, how the pathogenesis of these mutations is not well understood.[17]
Facioscapulohumeral muscular dystrophy	158900	DUX4	Facioscapulohumeral muscular dystrophy (FSHD) initially affects the muscles of the face, shoulders, and upper arms with progressive weakness. Symptoms usually develop in the teenage years. Some affected individuals become severely disabled. The pattern of inheritance is autosomal dominant, but there are a significant number of spontaneous mutations. Seminal research published in August 2010 documents that two defects are needed for FSHD, which for the first time provides a unifying theory for the underlying genetics of FSHD. The first is the deletion of D4Z4 repeats and the second is a "toxic gain of function" of the DUX4 gene.[4][18] [19] Facioscapulohumeral muscular dystrophy (FSHD) occurs both in males and females.
Limb-girdle muscular dystrophy	Multiple	Multiple	Limb-girdle muscular dystrophy is also called LGMD. Affects both boys and girls. LGMDs all show a similar distribution of muscle weakness, affecting both upper arms and legs. Many forms of LGMD have been identified, showing different patterns of inheritance (autosomal recessive vs. autosomal dominant). In an autosomal recessive pattern of inheritance, an individual receives two copies of the defective gene, one from each parent. The recessive LGMDs are more frequent than the dominant forms, and usually have childhood or teenage onset. The dominant LGMDs usually show adult onset. Some of the recessive forms have been associated with defects in proteins that make up the dystrophin-glycoprotein complex.[4] Though a person normally leads a normal life with some assistance, in some extreme cases, death from LGMD occurs due to cardiopulmonary complications.[20]
Myotonic muscular dystrophy	160900, 602668	DMPK, ZNF9	Myotonic muscular dystrophy is an autosomal dominant condition that presents with myotonia (delayed relaxation of muscles) as well as muscle wasting and weakness.[21] Myotonic dystrophy varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, eyes, and gastrointestinal tract. Myotonic muscular dystrophy type 1 (DM1), also known as Steinert disease, is the most common adult form of muscular dystrophy. It results from the expansion of a short (CTG) repeat in the DNA sequence of the DMPK (myotonic dystrophy protein kinase) gene. Myotonic muscular dystrophy type 2 (DM2) is much rarer and is a result of the expansion of the CCTG repeat in the ZNF9 (zinc finger protein 9) gene. While the exact mechanisms of action are not known, these molecular changes may interfere with the production of important muscle proteins.[4]
Oculopharyngeal muscular dystrophy	164300	PABPN1	Oculopharyngeal MD's age at onset: 40 to 70 years; symptoms affect muscles of eyelids, face, and throat followed by pelvic and shoulder muscle weakness, has been attributed to a short repeat expansion in the genome which regulates the translation of some genes into functional proteins.[4]

Research funding

The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. Please improve this article and discuss the issue on the talk page. (December 2010)

Within the United States, the three primary federally funded organizations that focus on muscular dystrophy research (Gene therapy, Regenerative medicine) etc. include the National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Institute of Child Health and Human Development (NICHD).^[4]

In 1966, the Muscular Dystrophy Association began its annual Jerry Lewis MDA Telethon, which has arguably done more to raise awareness of muscular dystrophy than any other event or initiative. Disability rights advocates, however, have criticized the Jerry Lewis Telethon for portraying victims of the disease as deserving pity rather than respect.^[22]

On December 18, 2001 the MD CARE Act was signed into law and amends the Public Health Service Act to provide research for the various muscular dystrophies. This law also established the Muscular Dystrophy Coordinating Committee to help focus research efforts through a coherent research strategy.^[23][24]

See also

• Muscular Dystrophy Association (USA)
• Muscular Dystrophy Campaign (UK)
• Muscular Dystrophy Canada (CAN)
• Muscle hypertrophy
• Myostatin

References

1. ^ Harrison's Principles of Internal Medicine. 2005. pp. 2527. doi:10.1036/0071402357. 
2. ^ Muscular Dystrophy Campaign Retrieved 9 April 2007.
3. ^ Emery AE (2002). "The muscular dystrophies". Lancet 359 (9307): 687–695. doi:10.1016/S0140-6736(02)07815-7. PMID 11879882. 
4. ^ ^{a b c d e f g h i j k} May 2006 report to Congress on Implementation of the MD CARE Act, as submitted by Department of Health and Human Service's National Institutes of Health
5. ^ http://www.mda.org/publications/fa-dmdbmd-what.html
6. ^ http://www.ninds.nih.gov/disorders/md/detail_md.htm#180483171
7. ^ http://www.columbia.edu/cu/md/pooraffectrecognition.pdf
8. ^ http://www.sciencedirect.com/science/article/pii/S1071909198800272
9. ^ http://psycnet.apa.org/journals/bul/86/2/250/
10. ^ Motlagh B, MacDonald JR, Tarnoplosky MA. Nutritional inadequacy in adults with muscular dystrophy. Muscle Nerve. 2005;31(6):713-8.
11. ^ http://www.physorg.com/news166974009.html
12. ^ R.M. Lehman & G.L. McCormack, 2001. Neurogenic and Myopathic Dysfunction pp. 802-803. In L. Pedretti and M Early Occupational Therapy Skills for Physical Dysfunction 5th ED St Louis MO: Mosby
13. ^ http://www.umm.edu/altmed/articles/muscular-dystrophy-000113.htm
14. ^ ^{a b} [1]: MD USA Website (accessed 03SEP2007)
15. ^ "Congenital Muscular Dystrophy (CMD)". MDA. http://www.mdausa.org/disease/cmd.html. Retrieved 27 April 2012. 
16. ^ ^{a b} http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm
17. ^ Emedicine re EDMD Retrieved 30 July 2007.
18. ^ Kolata, Gina (19 August 2010). "Reanimated 'Junk' DNA Is Found to Cause Disease". New York Times. http://www.nytimes.com/2010/08/20/science/20gene.html?_r=2&emc=eta1. Retrieved 29 August 2010. 
19. ^ Lemmers, Richard; Patrick J. van der Vliet, Rinse Klooster, Sabrina Sacconi, Pilar Camaño, Johannes G. Dauwerse, Lauren Snider, Kirsten R. Straasheijm, Gert Jan van Ommen, George W. Padberg, Daniel G. Miller, Stephen J. Tapscott, Rabi Tawil, Rune R. Frants, and Silvère M. van der Maarel (19 August 2010). "A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy". Science 329 (5999): 1650–3. doi:10.1126/science.1189044. PMID 20724583. http://www.sciencemag.org/cgi/content/abstract/science.1189044. 
20. ^ Jenkins, Simon P.R. (2005). Sports Science Handbook:I - Z.. Brentwood, Essex: Multi-Science Publ. Co.. pp. 121. ISBN 0906522-37-4. 
21. ^ Turner, C; Hilton-Jones D. (2010). "The myotonic dystrophies: diagnosis and management". J Neurol Neurosurg Psychiatry 81: 358–367. doi:10.1136/jnnp.2008.158261. PMID 20176601. http://jnnp.bmj.com/content/81/4/358.long. 
22. ^ Jon Wiener, "The End of the Jerry Lewis Telethon--It's About Time." TheNation.com, Sept. 2, 2011. http://www.thenation.com/blog/163119/end-jerry-lewis-telethon-its-about-time
23. ^ H.R. 717--107th Congress (2001): MD-CARE Act, GovTrack.us (database of federal legislation), (accessed Jul 29, 2007)
24. ^ Public Law 107-84, PDF as retrieved from NIH website

External links

• Muscular dystrophies at the Open Directory Project

v t e Muscular dystrophy The Nine Primary Muscular Dystrophies Congenital • dystrophin (Becker's, Duchenne) • Distal • Emery-Dreifuss • Facioscapulohumeral • Limb-girdle muscular dystrophy • Myotonic • Oculopharyngeal Related topics National/International Organizations Muscular Dystrophy Association (USA) • Muscular Dystrophy Canada • Myotonic Dystrophy Foundation US government Institutes and Legislation NINDS • NIAMS • NICHD • MD CARE Act • Genetic Information Nondiscrimination Act • Americans with Disabilities Act of 1990 National/International Events MDA Labor Day Telethon (USA) • Décrypthon (France) Recent or Ongoing Clinical Trials Stamulumab (MYO-029) M: MUS, DF+DRCT anat (h/n, u, t/d, a/p, l)/phys/devp/hist noco(m, s, c)/cong(d)/tumr, sysi/epon, injr proc, drug (M1A/3)

v t e Diseases of myoneural junction and muscle / neuromuscular disease (G70–G73, 358–359) Neuromuscular- junction disease autoimmune (Myasthenia gravis, Lambert–Eaton myasthenic syndrome) Myopathy/ congenital myopathy Muscular dystrophy (DAPC) AD Limb-girdle muscular dystrophy 1 · Oculopharyngeal · Facioscapulohumeral · Myotonic · Distal (most) AR Limb-girdle muscular dystrophy 2 · Congenital (Fukuyama, Ullrich, Walker–Warburg) XR dystrophin (Becker's, Duchenne) · Emery–Dreifuss Other structural collagen disease (Bethlem myopathy) · PTP disease (X-linked MTM) · adaptor protein disease (BIN1-linked centronuclear myopathy) · cytoskeleton disease (Nemaline myopathy, Zaspopathy) Channelopathy Myotonia Myotonia congenita · Thomsen disease · Neuromyotonia/Isaacs syndrome · Paramyotonia congenita Periodic paralysis Hypokalemic (Thyrotoxic) · Hyperkalemic Other Central core disease Mitochondrial myopathy MELAS · MERRF · KSS · PEO Other Inflammatory myopathy M: MUS, DF+DRCT anat (h/n, u, t/d, a/p, l)/phys/devp/hist noco(m, s, c)/cong(d)/tumr, sysi/epon, injr proc, drug (M1A/3)

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