Muscular dystrophy

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.

KEY TERMS

Autosomal dominant —A pattern of inheritance in which only one of the two copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. A person with an autosomal dominant disorder has a 50 percent chance of passing it to each of their offspring.

Autosomal recessive —A pattern of inheritance in which both copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. When both parents have one abnormal copy of the same gene, they have a 25 percent chance with each pregnancy that their offspring will have the disorder.

Becker muscular dystrophy (BMD) —A type of muscular dystrophy that affects older boys and men and usually follows a milder course than Duchenne muscular dystrophy.

Contracture —A tightening or shortening of muscles that prevents normal movement of the associated limb or other body part.

Distal muscular dystrophy (DD) —A form of muscular dystrophy that usually begins in middle age or later, causing weakness in the muscles of the feet and hands.

Duchenne muscular dystrophy (DMD) —The most severe form of muscular dystrophy, DMD usually affects young boys and causes progressive muscle weakness, usually beginning in the legs.

Dystrophin —A protein that helps muscle tissue repair itself. Both Duchenne muscular dystrophy and Becker muscular dystrophy are caused by flaws in the gene that tells the body how to make this protein.

Facioscapulohumeral muscular dystrophy (FSH) —This form of muscular dystrophy, also known as Landouzy-Dejerine disease, 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.

Limb-girdle muscular dystrophy (LGMD) —A form of muscular dystrophy that begins in late childhood to early adulthood and affects both men and women. It causes weakness in the muscles around the hips and shoulders.

Myotonic dystrophy —A form of muscular dystrophy, also known as Steinert's disease, that affects both men and women. It is characterized by delay in the ability to relax muscles after forceful contraction (myotonia) and wasting of muscles, as well as other abnormalities.

Oculopharyngeal muscular dystrophy —A type of muscular dystrophy that affects adults of both sexes, causing weakness in the eye muscles and throat.

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 of Medicine, 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, and Annotated Research Guide to Internet References. San Diego, CA: Icon Health Publications, 2003.

Sarnat, Harvey B. "Muscular Dystrophies." In Nelson Textbook 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/

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 Center School of Medicine. Available online at <www.hmc.psu.edu/healthinfo/m/musculardystrophy.htm> (accessed January 7, 2005).

L. Fleming Fallon, Jr., MD, DrPH

Muscular dystrophy

Definition

Muscular dystrophies (MD) are inherited disorders characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement, without a central or peripheral nerve abnormality. The muscles of the heart and other involuntary muscles are also affected in some forms of MD, and a few forms involve other organs as well. The major forms of muscular dystrophy include myotonic, Duchenne, Becker, limb-girdle, facioscapulohumeral, congenital, oculopharyngeal, distal, Emery-Dreifuss and Fukuyama muscular dystrophy.

Description

The commonest form of these inherited disorders is the Duchenne muscular dystrophy (DMD). The disorder was originally described in the mid-nineteenth century by the English physician Edward Meryon. At a meeting of the Royal Medical and Chirurgical Society in 1851, and later published in the transactions of the society, he described in detail the clinical presentation of Duchenne muscular dystrophy, beginning in early childhood with progressive muscle wasting and weakness and leading to death in late adolescence. Furthermore, his detailed histological studies led him to conclude that the muscle membrane or sarcolemma was broken down and destroyed.

Duchenne muscular dystrophy will usually produce symptoms between the ages of three and seven in young boys. It begins with a weakness in the pelvic area first and then progresses to the shoulder muscles. As the disorder escalates, the muscles enlarge although the muscle tissue is weak. The heart muscle will also enlarge, creating problems with the heartbeat that can be detected on an electrocardiogram. In most cases, the affected child has a waddling walk, often falls, has difficulty rising from a sitting position, has a difficult time climbing stairs, is unable to fully extend the arms and legs, and may develop scoliosis (an abnormally curved spine). In most cases, children with DMD are confined to a wheel chair between the ages of ten and twelve.

Most people with Becker muscular dystrophy (BMD) first experience difficulties between the ages of five and fifteen years, although onset in the third or fourth decade or even later can occur. By definition, patients with BMD are able to walk beyond age fifteen, while patients with DMD are typically in a wheelchair by the age of twelve. Patients with BMD have a reduced life expectancy, but most survive into the fourth or fifth decade. Mental retardation may occur in BMD, but it is not as common as in DMD. Cardiac (heart muscle) involvement occurs in BMD and may result in heart failure.

Myotonic muscular dystrophy (MMD) affects the muscles in the hands and feet. Limb-girdle muscular dystrophy (LGMD) begins late in childhood affecting mainly the muscles of the shoulders and hips. Facioscapulohumeral muscular dystrophy (FSHD) affects only the muscles of the upper arms, face and shoulder girdle. Landouzy-Dejerine muscular dystrophy (LDMD), which is transmitted by an autosomal dominant gene, affects the face, shoulder and lower leg muscles.

Other disorders related to muscular dystrophy include Steinert's disease, Thomsen's disease, and Pompe's disease. Steinert's disease affects both males and females, causing the muscles to be unable to relax after contracting, while Thomsen's disease causes a stiffness of the legs, hands and eyelids. Pompe's disease, which is a glycogen storage disease, affects the liver, heart, nerves and muscles.

Demographics

United States

The incidence of muscular dystrophy varies, depending on the specific type. Duchenne muscular dystrophy is the most common condition. It is inherited on the X chromosome, primarily affects boys, and is the most severe type of the disease. Although women with the defective gene are carriers, they usually show no symptoms. DMD has an inheritance pattern of 1 case per 3,500 live male births, and one-third of cases are due to spontaneous new mutations.

Becker muscular dystrophy is the second most common form, with an incidence of 1 case per 30,000 live male births. Like DMD, BMD is linked to the X chromosome. Other types of MD are rare. Limb-girdle muscular dystrophy includes several different illnesses, which can be inherited by both males and females, as can facioscapulohumeral muscular dystrophy.

International

The incidence of muscular dystrophies internationally is similar to that of the United States, however some types are especially frequent in certain populations and are rare elsewhere. For example, autosomal dominant distal muscular dystrophy occurs more often in Scandinavia than elsewhere, Fukuyama muscular dystrophy in Japan, oculopharyngeal muscular dystrophy in French Canada, and several autosomal recessive LGMD in communities in Brazil, North America, and the Middle East.

Causes and symptoms

All types of muscular dystrophy are inherited. They are caused by a defect in one or more of the genes that control muscle structure and function. Some types are inherited as a dominant gene abnormality, while others are inherited as a recessive gene abnormality or an X-linked recessive gene abnormality. In an X-linked recessive gene abnormality, the gene is on the X chromosome, one of the pair of chromosomes that determine a person's sex.

Both DMD and BMD are inherited X-linked recessive diseases affecting primarily skeletal muscle and the myocardium (heart muscle). Dystrophin, a large protein that stabilizes the plasma membrane during muscle contractions, is absent in DMD and reduced in BMD. This results

in an unstable muscle cell membrane and impaired function in the cell. Muscle fibers continually deteriorate and regenerate until the capacity for repair is no longer sufficient. Muscle fiber tissue is eventually replaced by fat and connective tissue. The abnormal gene for DMD and BMD is on the short arm of the X chromosome at position Xp21.

Two types of MMD are well recognized: noncongenital (NC-MMD, not present at birth) and congenital (CMMD, present at birth). In MMD, a DNA sequence within the gene on chromosome 19q 13.3, is repeated many times, leading to an enlarged, unstable area of the chromosome. Called a triplet repeat mutation, the flawed gene grows by sudden leaps when transmitted from generation to generation, causing the disease to occur at a younger age and in a more severe form (a phenomenon called anticipation). C-MMD patients have been shown to have substantially more repeats than those found in NC-MMD patients.

In FSHD, the abnormal gene is known to be near the end of chromosome 4. Exact DNA testing for diagnostic purposes is not yet available except in some cases, a detailed genetic analysis of a particular family can be accomplished.

Genetic studies with LGMD have identified one form linked to chromosome 15q, another form to chromosome 2p, and two more severe forms to 13ql2 and 17ql2-q21.

Symptoms can first appear during early childhood or late in adult life, depending on the type of muscular dystrophy.

• Duchenne muscular dystrophy—Symptoms usually begin between ages two and four. Because of a progressive weakening of leg muscles, the child falls frequently and has difficulty getting up from the ground. The child also has trouble walking or running normally. By age 12, most patients are unable to walk and are limited to a wheelchair. As the illness progresses, there also is an abnormal curvature of the spine.
• Becker muscular dystrophy—Symptoms are similar to those of DMD, but they are milder and begin later, usually between ages five and fifteen.
• Myotonic muscular dystrophy—Muscle myotonia may develop soon after birth or begin as late as early adulthood, and especially affects the hands, wrists and tongue. There also is wasting and weakening of facial muscles, neck muscles, and muscles of the wrists, fingers and ankles. Involvement of the tongue and throat muscles causes speech problems and difficulty swallowing. If the diaphragm and chest muscle also are involved, there may be breathing problems.
• Limb-girdle muscular dystrophy—Symptoms begin in late childhood or early adulthood. They include progressive muscle weakness in the shoulders and hips, together with breathing problems (if the diaphragm is involved). If illness also affects the heart muscle, there may be heart failure or abnormal heart rhythms.
• Facioscapulohumeral muscular dystrophy—Symptoms may begin during infancy, late childhood, or early adulthood. Usually, the first sign is facial weakness with difficulty smiling, whistling and closing the eyes. Later, there is difficulty raising the arms or flexing the wrists and/or ankles.

Diagnosis

The diagnosis of muscular dystrophy is made with a physical examination and diagnostic testing by the child's physician. During the examination, the child's physician obtains a complete prenatal and birth history and asks if other family members are known to have MD. In addition to a clinical history and a physical exam, others exams may be suggested:

• Serum creatine kinase—Measurement of serum (a blood component) concentration of creatine kinase is a simple and inexpensive diagnostic test for severe forms of dystrophy known to be associated with high concentrations of creatine in the blood. In DMD, serum creatine kinase values are raised from birth, and testing in newborns for early diagnosis could reduce the possibility of further affected boys in a family and improve medical assistance before the onset of symptoms.
• Electromyography—This test is important in the establishment of the myopathic (muscle disease not caused by nerve dysfunction) nature of the disease and for the exclusion of neurogenic (from the nerves) causes of weakness, including peripheral nerve disorders. Because electromyography is an invasive technique involving a needle stick, it is becoming less favored in the investigation of children, but it still has an important role in the diagnosis of adult disease.
• Muscle histology—The one unifying feature of the dystrophies is their similar muscle histological (in the tissues) findings, such as variation in muscle fiber size, muscle fiber death, invasion by macrophages (a versatile immune cell), and ultimately, replacement by fat and connective tissue. This picture is aggravated in the more severe forms of dystrophy, such as Duchenne type. However, in FSHD and LGMD, inflammatory changes in tissues are often the main features.
• Immunohistochemistry and mutation analysis—In some muscular dystrophies, certain proteins are deficient in muscle tissue. Immunohistochemistry involves methods of detecting the presence of these specific proteins in muscle cells or tissues. A diagnosis can be made when these protein deficiencies are identified. Analysis of genetic mutations associated with muscular dystrophies is also important for genetic counseling and prenatal diagnosis.

Treatment team

There are many professionals available to help the child with muscular dystrophy, depending on the patient's needs. These include physicians, orthopedic surgeons (bone specialists), physical therapists, orthotists (specialists on equipment to maintain posture and mobility), occupational therapists, dietitians, nurses, social workers , psychologists, teachers, religious advisers, staff from the Muscular Dystrophy Association, parents, and other persons with MD.

Physical therapy involves a program of stretching exercises to maintain muscle length and the flexibility of joints. Physical therapists also work with orthotists. Night splints, calipers, swivel walkers, and braces are some of the aids employed. Physical therapists are the main professionals involved in teaching parents the appropriate exercises and in making sure that any mobility aids are comfortable. Both physical therapy and hydrotherapy (water therapy) contribute significantly to mobility and respiratory function.

Treatment

Although there is no known cure for muscular dystrophy, exercise and physical therapy are recommended to maintain mobility for as long as possible. Corticosteroid drugs and gene therapies are being studied to help relieve the symptoms.

Specific treatment for muscular dystrophy is determined by the child's physician based on age, overall health, medical history, extent of the condition, type of condition, child's tolerance for specific medications, procedures or therapies.

Drug therapies

In children with Duchenne muscular dystrophy, corticosteroids (such as prednisone) may be prescribed to temporarily delay progression of their illness; however, some patients cannot tolerate this medication because of side effects. Powerful medications that suppress the immune system have been reported to help some patients, but their use is controversial. In patients with MMD, myotonia (abnormally long muscular contractions) may be treated with medications such as carbamazepine or phenytoin.

Gene therapy

With advances in molecular biology techniques, another method of treatment currently under intense investigation is somatic gene therapy . The idea is to introduce healthy immature cells into affected muscles, which would fuse and stimulate production of enough dystrophin to reverse the degeneration already taking place. Although this has been achieved successfully in mice, the benefit may not translate into humans. The mice cannot demonstrate muscle strength, and the laboratory-raised mice were not able to mount a rejection response that may occur in humans.

Other therapies

The orthopedic problems in children with MD lead to progressive weakness with walking difficulties, soft-tissue contractures, and spinal deformities. The role of the orthopedic surgeon is to correct deformities and help maintain the child's ambulatory status for as long as possible. The modalities available to obtain these goals include: functional testing; physical therapy; use of orthoses (specialized aids); fracture management; soft tissue, bone, and spinal surgeries; use of a wheelchair when indicated; and genetic and/or psychological testing.

Recovery and rehabilitation

To date, there is no known treatment, medicine, or surgery that will cure MD, or stop the muscles from weakening. The goal of treatment is to prevent deformity and allow the child to function as independently as possible at home and in the community.

Physical therapy

In general, patients are given supportive care, together with leg braces and physical therapy to maximize their ability to function in daily life. Stretching limbs to avoid tightened tendons and muscles is particularly important. When tightness of tendons develops (called contractures), surgery can be performed. When chest muscles are involved, respiratory therapy may be used to delay the onset of breathing problems. In addition, people with MD are given age-appropriate dietary therapy to help them avoid obesity. Obesity is especially harmful to patients with MD because it places additional strain on their already weak muscles. Unfortunately, many MD patients are at a high risk of obesity because their limited physical activity prevents them from exercising.

Wheelchair prescription

If the person with MD becomes nonambulatory, wheelchair mobility is essential. The wheelchair should complement the patient's lifestyle, providing comfort, safety, and functionality. Special attention should be given to the frame, seat, backrest, front rigging, rear wheels, and casters because of the functional weakness and contractures in the upper and lower extremities of patients with limb-girdle dystrophy. An accessible home and work environment and personal or public transportation with safe restraint systems for the wheelchair are also important.

Additional resources

Specific planning for vocational needs and desires may be coordinated with therapists. Resources within the community, such as the Parks and Recreation Department for activity programs, may be explored. Educational institutions, from public schools to community colleges and universities, have resources that may be used. Adaptive physical education program and Disabled Student Services generally are available for persons with MD.

Clinical trials

There are numerous open clinical trials for MD:

• An open-label pilot study of Oxatomide in steroid-naive DMD, sponsored by Cooperative International Neuromuscular Research Group;
• An open-label pilot study of Coenzyme Q10 in steroid-treated DMD, sponsored by Cooperative International Neuromuscular Research Group;
• Study of Inherited Neurological Disorders, sponsored by National Institute of Neurological Disorders and Stroke (NINDS);
• Study of Albuterol and Oxandrolone in Patients With FSHD, sponsored by the Food and Drug Administration Office of Orphan Products Development.

Updated information on clinical trials is available at the National Institutes of Health website for clinical trials at <www.clinicaltrials.org>.

Prognosis

The prognosis varies according to the type of MD and its progression. Some patients have only mild symptoms with a normal lifespan, whereas others have severe symptoms and die at a young age. For example, children with DMD often die before age 18 because of respiratory failure, heart failure, pneumonia or other problems. In persons with BMD, death tends to occur later. Some examples of complications associated with MD that lead to permanent, progressive disability are:

• deformities, such as scoliosis and joint contractures
• decreased mobility
• decreased ability to perform daily self-care tasks, such as bathing and dressing
• mental impairment (varies)
• cardiomyopathy (weakened heart muscle)
• respiratory failure

Special concerns

Genetic counseling is an important aspect of the care and evaluation of patients with DMD and BMD and their family members. A minority of female carriers have MD symptoms, but even in these symptomatic patients, correct diagnosis requires appropriate testing. In families in which an affected male has a known deletion or duplication of the dystrophin gene, testing for carrier status is performed accurately by testing possible carriers for the same mutation, the absence of which would exclude them as a carrier.

Resources

BOOKS

Parker, James N., and Philip M. Parker. The 2002 Official Patient's Sourcebook on Muscular Dystrophy. San Diego: Icon Group International, 2002.

Siegel, Irwin M. Muscular Dystrophy in Children: A Guide for Families. Gardena, CA: Scb Distributors, 1999.

Thompson, Charlotte. Raising a Child with a Neuromuscular Disorder: A Guide for Parents, Grandparents, Friends, and Professionals New York: Oxford Press, 1999.

Wolfson, Penny. Moonrise: One Family, Genetic Identity, and Muscular Dystrophy. New York: St. Martin's Press, 2003.

PERIODICALS

Emery, A. "The muscular dystrophies." The Lancet 359 (February 2002): 687–695.

OTHER

"Facts About Duchenne and Becker Muscular Dystrophies (DMD and BMD)" Muscular Dystrophy Association. (March 20, 2004). <http://www.mdausa.org/publications/fa-dmdbmd.html>.

"NINDS Muscular Dystrophy (MD) Information Page"

National Institute of Neurological Disorders and Stroke. (March 20, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/md.htm>.

ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718-3208. (520) 529-2000 or (800) 572-1717; Fax: (520) 529-5300. mda@mdausa.org. <http://www.mdausa.org/>.

Muscular Dystrophy Family Foundation. 2330 North Meridien Street, Indianapolis, IN 46208. (317) 923-6333 or (800) 544-1213; Fax: (317) 923-6334. mdff@mdff.org. <http://www.mdff.org/>.

Parent Project for Muscular Dystrophy Research. 1012 North University Blvd., Middletown, OH 45042. (413) 424-0696 or (800) 714-KIDS (5437); Fax: (513) 425-9907. ParentProject@aol.com. <http://www.parentprojectmd.org>.

Francisco de Paula Careta

Iuri Drumond Louro, MD, PhD

Muscular Dystrophy

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.

see also Gene Therapy; Genetic Testing; Inheritance Patterns; Prenatal Diagnosis; Triplet Repeat Disease.

Jeffrey M. Stajich

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>.

muscular dystrophy , any of several inherited diseases characterized by progressive wasting of the skeletal muscles. There are five main forms of the disease. They are classified according to the age at onset of symptoms, the pattern of inheritance, and the part of the body primarily affected.

Types of Muscular Dystrophy

The most common form of muscular dystrophy, Duchenne, was first described by the French physician Guillaume Benjamin Amand Duchenne in 1861. Most cases are caused by a recessive sex-linked gene located on the X chromosome and carried only by females. Each son of a carrier has a 50% chance of inheriting the gene and developing the disease. Each daughter has a 50% chance of inheriting the gene and becoming a carrier. In small number of "sporadic" cases there is no family history. The disease begins with leg weakness before age 3 and progresses rapidly, with death often occurring before age 30, often because of involvement of lung or heart muscle. Research has shown that the abnormal gene fails to produce an essential skeletal muscle protein called dystrophin. Becker's muscular dystrophy is similar to the Duchenne form, but appears somewhat later in life and progresses more slowly.

Fascioscapulohumeral muscular dystrophy primarily involves facial and shoulder muscles and affects both sexes. Symptoms can begin from adolescence to around age 40. It is caused by an autosomal dominant trait (at least one parent will have the disease). Progression is usually slow and severe disability is unusual.

Myotonic muscular dystrophy is another autosomally dominant disease affecting both sexes. It appears to be caused by the repetition of a section of DNA on chromosome 4. In a surprising development, researchers found that the number of repetitions on the chromosome increase and the disease becomes more severe with each generation. It is characterized by an inability of the muscles to relax properly after contraction and primarily affects the muscles of the hands and feet. It usually begins in adulthood and is often accompanied by cataracts, baldness, and abnormal endocrine function.

The limb-girdle form of the disease first affects the muscles of the hip and shoulder areas. Symptoms usually become apparent in late adolescence or early adulthood. Caused by an autosomal recessive trait (carried by a gene passed on by both asymptomatic parents), it can affect males and females alike. This form usually progresses slowly.

Treatment

There is no known cure for muscular dystrophy. Corticosteriods may slow the destruction of muscle tissue in persons with Duchenne muscular dystrophy, and phenytoin, procainamide, or quinine is used to treat delayed muscle relaxation in myotonic muscular dystrophy. Supportive measures and exercises can improve the quality of life and preserve mobility for as long as possible. Scientists have begun to identify the genetic abnormalities responsible for multiple dystrophy and hope that further understanding will lead to treatment. Genetic screening is recommended for all family members who might be carriers. Prenatal tests such as chorionic villus sampling and amniocentesis can detect some forms of muscular dystrophy early in a pregnancy.

Bibliography

See A. E. H. Emery, Muscular Dystrophy: The Facts (1994).

MUSCULAR DYSTROPHY

DEFINITION

Muscular dystrophy (MD) is the name for a group of disorders in which muscle size and strength gradually decrease over time. Nine different forms of the disorder have been discovered.

DESCRIPTION

The nine different forms of muscular dystrophy are usually distinguished by the part of the body they affect. They include the following:

• Duchenne muscular dystrophy (DMD). DMD primarily affects young boys. It causes weakness in the muscles that gets worse over time. The problem usually begins in the legs and then spreads to muscles in other parts of the body. It is the severest form of MD. DMD occurs in about 1 out of every 3,500 male births. About 8,000 boys and young men in the United States have the disorder. A milder form of the disorder occurs in a very few females.
• Becker muscular dystrophy (BMD). BMD affects older boys and young men. It is a milder form of MD than DMD, which occurs in about 1 in every 30,000 male births.
• Emery-Dreifuss muscular dystrophy (EDMD). EDMD is a very rare form of MD. It affects young boys exclusively. It causes contracture (permanent tightening) and weakness of the calf muscles and weakness in the shoulders and upper arms. It can also cause problems in the electrical signals that cause the heart to beat. Fewer than 300 cases of EDMD have been seen.
• Limb-girdle muscular dystrophy (LGMD). LGMD begins in later childhood or early adulthood. It affects both men and women. It causes weakness in the muscles around the hips and shoulders. LGMD has the greatest variety of symptoms of all forms of MD. In fact, researchers think it may actually consist of other forms of the disorder. Diagnosis of LGMD is difficult, and some patients with the disorder may have been diagnosed incorrectly in the past. The number of people with LGMD in the United States is probably a few thousand.
• Facioscapulohumeral muscular dystrophy (FSH). (pronounced FAY-shee-o-SKAP-yuh-lo-HYOOM-uh-ruhl) is also known as Landouzy-Dejerine disease. It begins in later childhood or early adulthood. It affects both men and women. FSH is characterized by weakness in the muscles of the face, shoulders, and upper arms. The hips and legs may also be affected. FSH occurs in about 1 out of every 2,000 people. About 13,000 people in the United States have the condition.
• Myotonic dystrophy. Myotonic (pronounced my-uh-TON-ik) dystrophy is also known as Steinert's disease. It affects both men and women. The disorder is usually seen first in the face, feet, and hands. It is characterized by an inability to relax the affected muscles. This condition is known as myotonia (pronounced my-uh-TO-nee-uh). Symptoms may first appear at any time between birth and adulthood. It is the most common form of MD. About 30,000 people in the United States have myotonic dystrophy.
• Oculopharyngeal muscular dystrophy (OPMD). Oculopharyngeal (pronounced OK-yuh-lo-fuh-RIN-jee-uhl) muscular dystrophy OPMD causes weakness in the eye muscles and throat. It affects adults of both sexes. It is most common among French Canadian families in Quebec and in Spanish American families in the southwestern United States.
• Distal muscular dystrophy (DD). DD begins in middle age or later. It causes weakness in the muscles of the feet and hands. It is most common in Sweden and rare in other parts of the world.
• Congenital muscular dystrophy (CMD). CMD appears at birth and progresses slowly thereafter. It causes a generalized weakness in muscles throughout the body. One form of the disorder is called Fukuyama, for a district in Japan where it is relatively common. Fukuyama CMD also causes mental retardation.

Muscular Dystrophy: Words to Know

Becker muscular dystrophy (BMD):

A type of muscular dystrophy that affects older boys and men and usually follows a milder course than DMD.

Contracture:

A permanent shortening and tightening of a muscle or tendon causing a deformity.

Distal muscular dystrophy (DD):

A form of muscular dystrophy that usually begins in middle age or later, causing weakness in the muscles of the feet and hands.

Duchenne muscular dystrophy (DMD):

The severest form of muscular dystrophy, usually affecting young boys, beginning in the legs, and resulting in progressive muscle weakness.

Facioscapulohumeral muscular dystrophy (FSH):

A form of muscular dystrophy that begins in late childhood to early adulthood; affects both men and women; and causes weakness in the muscles of the face, shoulders, and upper arms.

Limb-girdle muscular dystrophy (LGMD):

A form of muscular dystrophy that begins in late childhood to early adulthood; affects both men and women; and causes weakness in the muscles around the hips and shoulders.

Myotonic dystrophy:

A form of muscular dystrophy that affects both men and women and causes generalized weakness in the face, feet, and hands.

Oculopharyngeal muscular dystrophy (OPMD):

A form of muscular dystrophy that affects adults of both sexes and causes weakness in the muscles of the eyes and throat.

CAUSES

All forms of muscular dystrophy are caused by wasting of muscle tissue. Muscle cells die, and muscles become weaker and unable to perform their normal functions. Researchers are still uncertain how this loss of muscle function takes place. They believe that cells may lose their ability to produce certain muscle proteins. Proteins are essential chemicals that occur in all cells and have many different functions. For example, they act as building blocks for cells and as enzymes. Enzymes are special kinds of proteins that control the rate at which chemical reactions take place in cells.

Researchers believe that some forms of MD occur because some muscle proteins are absent or present in smaller-than-average amounts. In such cases, muscle tissue becomes weak. Other muscle proteins may be needed to repair damage in muscle tissue. If those proteins are absent, muscles that are damaged cannot be repaired. In most cases, the connection between absent muscle proteins or reduced amounts of proteins and various forms of MD is simply not yet known.

What scientists do know is that MD is almost entirely a genetic disorder. A genetic disorder is a medical problem caused by defects in a person's genes. Genes are chemical units found within cells that carry essential information telling the cell what functions it should perform. Every person gets two sets of genes, one from each parent. Under most circumstances, the two sets of genes merge to produce a normal set of instructions. A cell follows those instructions to perform a normal set of functions.

Occasionally, a person inherits faulty genes from one or both of his or her parents. In such cases, the instructions provided to a cell can be incorrect and the cell is unable to perform its normal functions.

In the case of MD, a person may receive a single faulty gene from one parent or a pair of faulty genes, one from each parent. A single faulty gene may cause no problem at all. In that case, the person is said to be a carrier. A carrier can transmit the faulty gene to his or her own children. But it will not interfere with the person's own health.

In other cases, one faulty gene is all it takes to cause some form of MD. For example, DMD, FSH, OPMD, and some forms of LGMD and DD are thought to be caused by a single faulty gene. The faulty gene may make it impossible for muscle cells to function as they should. Muscle tissues weaken, and some form of muscular dystrophy results.

Other forms of MD require the presence of two faulty genes, one from each parent. CMD and some forms of LGMD and DD are thought to be caused by this mechanism. Again, the two faulty genes carry incorrect information to a cell and the cell does not function normally. It produces faulty muscle protein, an insufficient amount of the protein, or no protein at all. Muscle tissue weakens and dies, and MD results.

SYMPTOMS

All forms of MD have one characteristic in common—muscular weakness. Other symptoms differ, however, depending on the type of MD involved.

DMD Symptoms

The first symptoms of DMD appear during preschool years. The disorder affects the legs first. A boy has trouble walking and maintaining balance. In most cases, he begins walking three to six months later than average. As his calf muscles begin to weaken, he may change the way he walks. He places his legs farther apart in order to maintain balance. Walking this way produces a waddling effect that is characteristic of DMD.

Contractures usually begin at about the age of five or six. They affect the calf muscles most severely, pulling the foot down and back. This forces a boy to walk on his tiptoes. Balance becomes more of a problem. As a result, falls and broken bones become common at this age. By the age of nine or ten, a boy with DMD might not be able to climb stairs or stand by himself. Most DMD patients have to use a wheelchair by the age of twelve.

FAULTY GENES AND MD

Sometimes faulty genes occur on the Y chromosome but not the X chromosome. Chromosomes are structures in cells that contain many genes. Women have two X chromosomes and no Y chromosomes. Men have one X chromosome and one Y chromosome. Faulty genes that occur in Y chromosomes are only present in men. This explains why some forms of muscular dystrophy affect men only. Men inherit those faulty genes, but women do not.

Muscles in other parts of the body are also weakened. When muscles in the upper body are affected, scoliosis (see scoliosis entry), or curvature of the spine, may result. The most serious problem, however, affects the muscles of the diaphragm. The diaphragm provides the in-and-out force that allows a person to breathe and to cough. As the diaphragm weakens, breathing becomes more difficult and patients will have less energy and stamina. They also become more subject to infection because they cannot cough up infectious agents that get into their lungs. Young men with DMD can live into their twenties provided they have mechanical aids to help with their breathing and good respiratory (breathing system) hygiene.

About a third of the boys with DMD also have learning disorders. These disorders can include problems with learning by ear and trouble paying attention to some tasks. Specialized educational problems can help compensate for these disorders.

BMD Symptoms

The symptoms of BMD usually appear in late childhood to early adulthood. They are similar to those of DMD, but they are usually less severe. They may also develop at a different rate and in a different pattern. For example, young men with BMD can often walk on their own into their twenties or early thirties. Scoliosis may also develop, but it is less severe and develops more slowly. One symptom that is more serious in BMD than DMD involves heart problems. These problems include irregular heartbeats and congestive heart failure. Symptoms related to heart problems include fatigue, shortness of breath, chest pain, and dizziness. Respiratory problems may also develop, requiring the use of a mechanical device to help the patient breathe.

EDMD Symptoms

EDMD usually begins in early childhood. The first symptom is likely to be contractures, which is a permanent shortening of a muscle. Muscle weakness then appears in the shoulders, upper arms, and calves. Most men with EDMD survive into middle age. As with BMD, heart problems may develop and can cause death.

LGMD Symptoms

At least two forms of LGMD occur. One develops during childhood and the other in the teens or twenties. The major symptom is weakening of muscles in the center of the body. Contractures may occur, and most people lose the ability to walk about twenty years after their disorder is diagnosed. In some people, respiratory problems may require the use of a mechanical device to assist with breathing.

FSH Symptoms

FSH varies in its severity and age of onset. Symptoms can begin anywhere from childhood to the early twenties. Symptoms tend to be more severe when the disorder appears earlier. The condition mostly affects muscles of the face, shoulders, and upper arms, although hips and legs may also be affected. Children with FSH often develop partial or complete deafness.

Symptoms of Myotonic Dystrophy

Symptoms of myotonic dystrophy include facial weakness, a slack (loose) jaw, drooping eyelids, and muscle wasting in the forearms and calves. A person with this dystrophy has difficulty letting go of an object, especially if it's cold. Myotonic dystrophy affects heart muscles, causing irregular heartbeats, and the muscles of the digestive system, leading to digestion problems and constipation.

Myotonic dystrophy can also affect other body systems. It can cause cataracts (see cataracts entry), destruction of the retina, mental retardation (see mental retardation entry), skin disorders (see skin disorders entry), wasting of the testicles, sleep problems (see insomnia entry), and diabetes-like problems (see diabetes mellitus entry). Most people with this type of dystrophy are severely disabled within twenty years of first diagnosis. They usually do not require a wheelchair, however.

Symptoms of OPMD

OPMD usually begins when a person has reached his or her thirties or forties. The disorder affects muscles controlling the eyes and throat. Symptoms include drooping eyelids and difficulty swallowing. Muscle weakness later spreads to the face, neck, and sometimes the upper limbs. Difficulty in swallowing can result in problems of the upper respiratory system. Among the most serious of these problems is pneumonia (see pneumonia entry).

Symptoms of DD

DD usually begins in the twenties or thirties. It first appears as a weakness in the hands, forearms, and lower legs. One of the first symptoms may be difficulty with fine movements, such as typing or fastening buttons. Symptoms usually progress slowly. The disorder seldom affects a person's normal life span.

Symptoms of CMD

CMD is marked by severe muscle weakness from birth. Infants with the disorder cannot control their muscles and tend to flop around. Nonetheless, children with CMD may learn to walk, with or without a supporting device, such as crutches. Many live into young adulthood and even beyond. Fukuyama CMD is a far more serious disorder, however. Children with this condition seldom learn to walk and suffer severe mental retardation. They generally die in childhood.

DIAGNOSIS

Diagnosis begins with a medical history and a complete physical examination. A medical history is important to find out if dystrophy has occurred in other family members. Since the disorder is hereditary, family patterns are helpful in diagnosing the condition. A physical examination is necessary to rule out conditions with similar symptoms.

A number of laboratory tests are available for diagnosing MD. These tests include:

• Blood levels of creatine kinase (CK; pronounced KREE-uh-teen KIE-nase). CK is an enzyme present in muscle tissue. Its production increases when muscle tissue is damaged.
• Muscle biopsy. A biopsy is a procedure by which a small sample of tissue is removed with a needle. The sample can then be studied under a microscope. Changes in muscle tissue can be observed, indicating the presence of a dystrophy.
• Electromyogram (EMG; pronounced e-LEK-tro-my-o-gram). An EMG is an electrical test to see how well muscles are functioning. If muscles do not respond normally to the test, a dystrophy may be present.
• Genetic tests. It is now possible to examine the genes present in a person's cells and identify genes that are faulty.
• Other tests for specific forms of MD. Specific tests can be conducted for certain types of MD. For example, a hearing test can be used to help diagnose FSH in children.

Most doctors with experience in dealing with MD can diagnose the disorder quite easily. In some cases, however, MD can be confused with other diseases that have similar symptoms. For example, the disorder known as myasthenia gravis (pronounced MY-uhs-THEE-nee-uh GRA-vuhs) affects the site where nerves and muscles come together. Its symptoms are somewhat similar to those of some forms of MD.

TREATMENT

There are currently no cures for any form of muscular dystrophy. A few drugs have been found that slow the progress of some forms of MD. For example, prednisone (pronounced PRED-nih-zone), a corticosteroid (pronounced kor-tih-ko-STIHR-oid), slows the progress of DMD. Generally speaking, however, drugs have a limited and uncertain value in the treatment of MD.

The primary goal of treatment programs for MD is to prevent complications. The major complications are decreased ability to move on one's own, contractures, scoliosis, heart defects, and respiratory problems.

Physical Therapy

Regular stretching exercises help prevent or delay contractures. Braces may be used to help support ankles, feet, legs, and other body parts with weakened muscles. Patients can sometimes be taught to use another set of muscles in place of muscles damaged by MD. A program of regular, light exercise can help keep muscles in good condition.

Surgery

Surgery may be necessary to correct some severe symptoms of MD. Contractures can be treated, for example, by cutting the damaged muscle. The muscle is then held in place until it grows back normally. In FSH, the shoulder blade can be braced to compensate for muscle weakness. For a person with OPMD, eyelids can be lifted by a surgical procedure to correct for drooping eyelids. Scoliosis can sometimes be corrected by back surgery. In this surgery, the vertebrae that make up the spine are fused (fixed) together. Steel rods are then inserted and attached to the vertebrae to keep the spine in a straight, stiff position.

Occupational Therapy

The purpose of occupational therapy is to help patients find ways of making up for their loss of strength and dexterity. Strategies may include changes in the home environment, learning to use special utensils and dressing aids, and use of a wheelchair and communication devices, such as hearing aids.

Nutrition

Good nutrition helps promote general health in all forms of MD. No special diet is needed or has been shown to relieve any of its symptoms, however.

Cardiac Care

EDMD and BMD may require certain kinds of treatment for heart problems. For example, drugs such as nifedipine (pronounced nie-FED-uh-peen) help maintain a regular heartbeat. An artificial pacemaker may also need to be installed in patients with an irregular heartbeat.

Respiratory Care

Weakness in diaphragm muscles can be a very serious condition that may result in a person losing the ability to breathe on his or her own. In such cases, a mechanical device may be needed to help the patient breathe. For example, air may be administered through a face mask or mouthpiece. Or a tracheotomy (pronounced TRAY-kee-OT-uh-mee) may be necessary. In a tracheotomy, a tube is inserted through a hole cut in the throat. Air can then be provided directly to the person's respiratory system.

Good lung hygiene is always necessary. Without proper care, infections of the lungs are common. Such infections can easily lead to pneumonia and even death. Patients with MD may also need to learn techniques for coughing. The normal cough reaction is usually difficult because of damaged muscles. But coughing is necessary to expel foreign particles that can cause disease and infection.

Experimental Treatments

Two experimental procedures may hold some promise for treating MD. One of these procedures is called myoblast transfer. In this procedure, millions of immature muscle cells are injected into a patient's damaged muscle. The goal of the procedure is to provide the person's body with normal, healthy cells that may be able to function in place of damaged ones. Thus far, there seems to be no evidence that this procedure is successful, although research continues in the hope of success in the future.

The second procedure is gene therapy. In gene therapy, a person with MD is injected with artificially produced genes that are correct copies of the faulty genes in their body. The hope is that the correct genes will function in cells the way the faulty genes are supposed to but don't. Gene therapy is a very difficult task complicated with many side effects. However, many researchers believe that it may be the most likely way of curing MD.

PROGNOSIS

The expected lifetime for a male with DMD has increased significantly in the past two decades. Most young men will now live into their early or mid-twenties. The main cause of death is respiratory infection.

Prognosis for other forms of MD is highly variable. It depends very much on the age at which symptoms first appear and how severe those symptoms are. People with BMD, EDMD, and myotonic dystrophy may have normal life spans. The critical issue for people with these disorders is attention to and care for heart problems that may develop.

PREVENTION

There is no way to prevent any form of MD. Some forms of the disorder can now be detected by genetic tests. Parents can have their unborn children tested for these forms of muscular dystrophy. They can then use that information for family planning purposes.

FOR MORE INFORMATION

Books

Bergman, Thomas. Precious Time: Children Living With Muscular Dystrophy (Don't Turn Away). Milwaukee, WI: Gareth Stevens, 1996.

Emery, Alan. Muscular Dystrophy: The Facts. Oxford Medical Publication, 1994.

Organizations

The Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718. (520) 529–2000; (800) 572–1717. http://www.mdausa.org.

muscular dystrophy n. a group of muscle diseases, marked by weakness and wasting of selected muscles, in which there is a recognizable pattern of inheritance. The affected muscle fibres degenerate and are replaced by fatty tissue. The most common form is Duchenne muscular dystrophy, which is nearly always restricted to boys and usually begins before the age of four. The child has a waddling gait and lordosis of the lumbar spine. The calf muscles – and later the shoulders and upper limbs – often become firm and bulky. See also Becker muscular dystrophy, dystrophia myotonica (myotonic dystrophy).

Muscular Dystrophy

What Is Muscular Dystrophy?

Who Gets Muscular Dystrophy?

What Causes Muscular Dystrophy?

Muscles under a Microscope

What Are the Symptoms of the Dystrophies?

How Is Muscular Dystrophy Diagnosed?

How Is Muscular Dystrophy Treated?

Resources

Muscular dystrophy (DIS-tro-fee) is a group of inherited disorders in which there is a gradual deterioration and weakening of muscles in the body.

KEYWORDS

for searching the Internet and other reference sources

Duchenne

Muscular disorders

Neurology

What Is Muscular Dystrophy?

The term “muscular dystrophy” actually includes a group of disorders that affect different muscles in the body, and that may range from mild to severe. Although all of the muscular dystrophies are known to be caused by genes*, the way in which the genes produce the disorder is as yet only partly understood.

*genes

are chemicals in the body that help determine a person’s characteristics, such as hair or eye color. They are inherited from a person’s parents and are contained in the chromosomes found in the cells of the body.

The muscles that become weakened in muscular dystrophy are mostly the voluntary muscles, those that we can control when we want to move different parts of the body. Another name for voluntary muscle is skeletal muscle. The weakness is usually symmetrical; that is, it occurs more or less equally on both sides of the body. Muscle deterioration is also progressive, or gradually increasing over time. There is no pain connected with the weakening condition, although there may be some cramps and stiffness. Mental retardation sometimes accompanies this condition.

Who Gets Muscular Dystrophy?

All types of muscular dystrophy are uncommon. Still, numbers of individuals affected range in the tens of thousands. Many people have come to know something about muscular dystrophy through the efforts of the famous American comedian and actor Jerry Lewis, who has appeared on television on behalf of the Muscular Dystrophy Association. Similar media appeals, such as the Telethon in France, have raised public awareness about the disease in other countries.

The most common and severe form of the disorder, called Duchenne (du-SHEN) muscular dystrophy, affects about 2 in 1,000 young boys. In the United States, it has been estimated that 40,000 boys and young men are afflicted with this form. In western Europe, an estimated 70,000 are affected. The incidence* is believed to be comparable throughout the world. Muscular dystrophy affects all races, ethnic groups, and social classes equally.

*incidence

means rate of occurrence.

What Causes Muscular Dystrophy?

Whether or not someone has a form of muscular dystrophy has already been determined through hereditary factors by the time they are born (even though its effects are not apparent at birth). It also means that the disease is not in any way contagious, and that it is not brought on by anything that might happen in one’s everyday life.

The defective gene that causes Duchenne muscular dystrophy is located on the X chromosome*. The disorder is therefore said to be sex-linked. It also is recessive, which means that females who inherit the defective gene will not usually develop the disease (because they need to have the defective gene on both X chromosomes) but are carriers of it. They can pass it on to the next generation. Affected males always inherit the gene for Duchenne

*chromosome

(KRO-mo-som) is α threadlike structure inside cells on which the genes are located. The X chromosome is one of two that determine whether a person is male or female. If you have two X chromosomes, then you are female; if you have one X and one Y chromosome, then you are male.

muscular dystrophy from their mothers, and each male born to a mother who is a carrier for the disease has a 50-50 chance of inheriting the gene.

Myotonic (mi-o-TON-ik) dystrophy, an adult form of the disorder, is inherited as an autosomal dominant. Autosomal means that the gene that causes the disorder is not located on a sex chromosome. Dominant means that just one defective gene in a pair is able to produce the disease. Males and females are equally affected by the faulty gene, and both can transmit the disease to their children.

Other types of muscular dystrophy follow various different patterns of inheritance, and they can affect both children and adults.

Muscles under a Microscope

The gene responsible for the Duchenne form of muscular dystrophy was discovered in 1986. That was an important breakthrough, but scientists still needed to know how the gene caused muscle weakness. The following year, a protein that was named dystrophin (DIS-tro-fin) was found to be absent in the muscles of Duchenne patients and present in normal tissue. Therefore, the defective Duchenne gene does not produce dystrophin, while the same gene in its normal form does produce this protein. To understand why dystrophin is important in muscle function, a powerful microscope is needed.

Seen under a microscope, muscles are made up of bundles of individual muscle fibers. Under greater magnification, each fiber is seen to have an outer membrane. Dystrophin is believed to be responsible for maintaining the structure of the muscle fiber membrane. Without it, the membrane tends to fall apart and become “leaky” One of the substances that leaks out from inside the muscle fibers is creatine kinase (KREE-a-tin KI-naze), which is needed for the chemical reactions that produce energy for muscle contraction.

In other types of muscular dystrophy, the defect lies in an abnormality in another substance closely associated in function with dystrophin.

What Are the Symptoms of the Dystrophies?

There are several forms of muscular dystrophy. Some experts have listed as many as 20 types. Classification of types is based upon a persons age at the start of the disease, the location of the muscles affected, the rate at which the disorder progresses, and the pattern of inheritance. The following are signs and symptoms of the more common and well-defined forms.

Duchenne Muscular Dystrophy

The signs of Duchenne muscular dystrophy may not be noticed until ages 3 to 7, when the young boy is likely to start having difficulty walking. (Because of the way it is inherited, only boys usually have Duchenne muscular dystrophy.) Another characteristic sign is that the calf muscles, although becoming weaker, are enlarged partly because of accumulating deposits of fat in them.

Muscle weakness steadily advances from the lower to the upper body, and a wheelchair is usually needed by about age 12. Complications such as scoliosis (side-to-side curving of the spine) and lung infections commonly occur in the teen years, and the person may not live past his late teens or early twenties.

Becker Muscular Dystrophy

In this form, the signs and symptoms are the same as those of Duchenne muscular dystrophy, but begin later in life and progress more slowly. The same gene that causes the Duchenne form is responsible, but its defects are less damaging to muscle. Most affected men must eventually use a wheelchair, but some do not, and many live past middle age.

Myotcnic Dystrophy

Myotonic dystrophy usually develops in adulthood, but may occur as early as infancy. Males and females are affected equally. The characteristic symptom is myotonia, a delayed relaxation of muscle after it has contracted. Weakness commonly occurs in the muscles of the hands, face, neck, forearms, and lower legs.

Unlike other dystrophies, myotonic dystrophy may involve parts of the body other than the voluntary muscles. For example, the heart rate may be abnormally slowed. Cataracts may develop in the eyes. As in other dystrophies, mental retardation sometimes accompanies the condition. Nonetheless, people with mild forms of myotonic dystrophy may have relatively normal lives and survive beyond middle age.

What’s in a Name?

The word “dystrophy” comes originally from the Greek “dys,” which means “difficult” or “faulty,” and “trophe,” meaning “nourishment.” This word was chosen many years ago because it was at first believed that poor nourishment of the muscles was in some way to blame for muscular dystrophy. Today we know that muscle wasting in the disorder is caused by defective genes rather than poor nutrition.

The “Duchenne” in Duchenne muscular dystrophy may have been a bit of a misnomer as well. The French neurologist Guillaume Benjamin Amand Duchenne (1806-1875) described the disorder in detail in 1868. However, recent research has shown that the English physician Edward Meryon (1809-1880) had independently described the condition several years before Duchenne.

Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral (fay-she-o-skap-yoo-lo-HU-me-ral) muscular dystrophy gets its long name from the fact that it weakens the muscles of the face, shoulders (the scapula is the shoulder blade), and upper arms (the humerus is the upper arm bone). Facial expression is altered, and the shoulders tend to droop. Both males and females are affected, and the progression of symptoms is usually slow. Symptoms most often begin to appear between the ages of 10 and 40.

Limb Girdle Muscular Dystrophy

Muscle weakness in this form occurs mostly around the hips and shoulders (limb girdles). Symptoms may eventually extend to other muscles. Often, however, worsening of the condition is slow. Both sexes are affected, and symptoms may begin in late childhood or early adult life.

How Is Muscular Dystrophy Diagnosed?

A doctor may suspect that someone has muscular dystrophy just by observing certain signs of muscle weakness. If someone in the patients immediate family is known to have the disorder, the diagnosis becomes clearer.

To confirm the diagnosis, a blood test may be performed to look for high levels of creatine kinase, mentioned earlier as a sign of Duchenne muscular dystrophy. Blood samples may also be analyzed for defective genes, and can help determine the specific type of the disorder. Other tests can measure muscle activity, and a muscle biopsy, in which a tiny sample of muscle tissue is removed to be examined under the microscope, can show specific abnormalities.

How Is Muscular Dystrophy Treated?

At present there is no cure for muscular dystrophy. Sometimes treatment with steroids can slow progress of muscular weakness. Treatment is aimed at maintaining general good health and mobility for as long as possible. An important goal is preventing scoliosis and often fatal lung infection. Moderate exercise, physical therapy, the use of braces, and sometimes surgery can assist walking.

Genetic counselors, using medical tests and family history, can help prospective parents make informed decisions about having children. The disease can be diagnosed in a baby before it is born; this is called prenatal testing.

Meanwhile, medical scientists in the laboratory are working on ways to attack the cause of muscular dystrophy directly, through a technique called gene therapy.

See also

Genetic Diseases

Scoliosis

Resources

Emery, Alan E. M. Muscular Dystrophy: The Facts. Oxford: Oxford University Press, 1994. This book provides in nontechnical language much helpful information about the disorder for patients and their caregivers.

Muscular Dystrophy Association provides general information on its website.
http://www.mdusa.org/

Muscular Dystrophy Association of Canada also provides information on its website.
http://www.mdac.ca/

muscular dystrophy Any of a group of hereditary disorders in which the characteristic feature is progressive weakening and atrophy of the muscles. The commonest type, Duchenne muscular dystrophy, affects boys, usually before the age of four. Muscle fibres degenerate, to be replaced by fatty tissue.

mus·cu·lar dys·tro·phy • n. a hereditary condition marked by progressive weakening and wasting of the muscles.