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Table of Contents (click to jump to sections)IntroductionWhat is muscular dystrophy?What causes MD?How many people have MD?How does MD affect muscles?Are there other MD-like conditions?How do the muscular dystrophies differ?How are the muscular dystrophies diagnosed?How are the muscular dystrophies treated?What is the prognosis?What research is being done?Where can I get more information?GlossaryIntroduction
The first historical account of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that caused progressive weakness in boys. Six years later, another scientist reported on two brothers who developed generalized weakness, muscle damage, and replacement of damaged muscle tissue with fat and connective tissue. At that time the symptoms were thought to be signs of tuberculosis. 

In the 1850s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of 13 boys with the most common and severe form of the disease (which now carries his name-Duchenne muscular dystrophy). It soon became evident that the disease had more than one form, and that these diseases affected people of either sex and of all ages. 
topWhat is muscular dystrophy?
Muscular dystrophy (MD) refers to a group of more than 30 genetic diseases that cause progressive weakness and degeneration of skeletal muscles used during voluntary movement. The word dystrophy is derived from the Greek dys, which means "difficult" or "faulty," and troph, or "nourish." These disorders vary in age of onset, severity, and pattern of affected muscles. All forms of MD grow worse as muscles progressively degenerate and weaken. The majority of patients eventually lose the ability to walk. 

Some types of MD also affect the heart, gastrointestinal system, endocrine glands, spine, eyes, brain, and other organs. Respiratory and cardiac diseases are common, and some patients may develop a swallowing disorder. MD is not contagious and cannot be brought on by injury or activity. 
topWhat causes MD?
All of the muscular dystrophies are inherited and involve a mutation in one of the thousands of genes that program proteins critical to muscle integrity. The body's cells don't work properly when a protein is altered or produced in insufficient quantity (or sometimes missing completely). Many cases of MD occur from spontaneous mutations that are not found in the genes of either parent, and this defect can be passed to the next generation. 

Genes are like blueprints: they contain coded messages that determine a person's characteristics or traits. They are arranged along 23 rod-like pairs of chromosomes, * with one half of each pair being inherited from each parent. Each half of a chromosome pair is similar to the other, except for one pair, which determines the sex of the individual. Muscular dystrophies can be inherited in three ways: 
- Autosomal dominant inheritance occurs when a child receives a   normal gene from one parent and a defective gene from the other parent.   Autosomal means the genetic mutation can occur on any of the 22 non-sex   chromosomes in each of the body's cells. Dominant means only one parent needs   to pass along the abnormal gene in order to produce the disorder. In families   where one parent carries a defective gene, each child has a 50 percent chance   of inheriting the gene and therefore the disorder. Males and females are   equally at risk and the severity of the disorder can differ from person to   person.   
- Autosomal recessive inheritance means that both parents must   carry and pass on the faulty gene. The parents each have one defective gene   but are not affected by the disorder. Children in these families have a 25   percent chance of inheriting both copies of the defective gene and a 50   percent chance of inheriting one gene and therefore becoming a   carrier, able to pass along the defect to their children. Children of   either sex can be affected by this pattern of inheritance.   
- X-linked (or sex-linked) recessive inheritance occurs   when a mother carries the affected gene on one of her two X chromosomes and   passes it to her son (males always inherit an X chromosome from their mother   and a Y chromosome from their father, while daughters inherit an X chromosome   from each parent). Sons of carrier mothers have a 50 percent chance of   inheriting the disorder. Daughters also have a 50 percent chance of inheriting   the defective gene but usually are not affected, since the healthy X   chromosome they receive from their father can offset the faulty one received   from their mother. Affected fathers cannot pass an X-linked disorder to their   sons but their daughters will be carriers of that disorder. Carrier females   occasionally can exhibit milder symptoms of MD. 

*Terms in Italics are defined in the glossary.
topHow many people have MD?
MD occurs worldwide, affecting all races. Its incidence varies, as some forms are more common than others. Its most common forms in children, Duchenne and Becker muscular dystrophy, alone affect approximately 1 in every 3,500 to 5,000 boys, or between 400 and 600 live male births each year in the United States.** Some types of MD are more prevalent in certain countries and regions of the world. Most muscular dystrophies are familial, meaning there is some family history of the disease. 

** Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, July 27, 2005
topHow does MD affect muscles?
Muscles are made up of thousands of muscle fibers. Each fiber is actually a number of individual cells that have joined together during development and are encased by an outer membrane. Muscle fibers that make up individual muscles are bound together by connective tissue. 

Muscles are activated when an impulse, or signal, is sent from the brain along the peripheral nerves (nerves that connect the central nervous system to sensory organs and muscles) to the neuromuscular junction (the space between the nerve fiber and the muscle it activates). There, a release of the chemical acetylcholine triggers a series of events that cause the muscle to contract. 

The muscle fiber membrane contains a group of proteins-called the dystrophin-glycoprotein complex-which prevents damage as muscle fibers contract and relax. When this protective membrane is damaged, muscle fibers begin to leak the protein creatine kinase (needed for the chemical reactions that produce energy for muscle contractions) and take on excess calcium, which causes further harm. Affected muscle fibers eventually die from this damage, leading to progressive muscle degeneration. 

Although MD can affect several body tissues and organs, it most prominently affects the integrity of muscle fibers. The disease causes muscle degeneration, progressive weakness, fiber death, fiber branching and splitting, phagocytosis (in which muscle fiber material is broken down and destroyed by scavenger cells), and, in some cases, chronic or permanent shortening of tendons and muscles. Also, overall muscle strength and tendon reflexes are usually lessened or lost due to replacement of muscle by connective tissue and fat. 
topAre there other MD-like conditions?
There are many other heritable diseases that affect the muscles, the nerves, or the neuromuscular junction. These diseases may produce symptoms that are very similar to those found in some forms of MD (such as inflammatory myopathy, progressive muscle weakness, mental impairment, and cardiomyopathy) but they are caused by different genetic defects. The sharing of symptoms among multiple neuromuscular diseases, and the prevalence of sporadic cases in families not previously affected by MD, often makes it difficult for MD patients to obtain a quick diagnosis. Studies of other related muscle diseases may, however, contribute to what we know about MD. 
topHow do the muscular dystrophies differ?
There are nine major groups of the muscular dystrophies. The disorders are classified by the extent and distribution of muscle weakness, age of onset, rate of progression, severity of symptoms, and family history (including any pattern of inheritance). Although some forms of MD become apparent in infancy or childhood, others may not appear until middle age or later. Overall, incidence rates and severity vary, but each of the dystrophies causes progressive skeletal muscle deterioration, and some types affect cardiac muscle. 

There are four forms of MD that begin in childhood:

Duchenne MD is the most common childhood form of MD, as well as the most common of the muscular dystrophies overall, accounting for approximately 50 percent of all cases. It affects approximately one in 3,500 male births. Because inheritance is X-linked recessive (caused by a mutation on the X, or sex, chromosome), Duchenne MD primarily affects boys, although girls and women who carry the defective gene may show some symptoms. About one-third of the cases reflect new mutations and the rest run in families. Sisters of boys with Duchenne MD have a 50 percent chance of carrying the defective gene. 

Duchenne MD usually becomes apparent when an affected child begins to walk. Progressive weakness and muscle wasting (a decrease in muscle strength and size) caused by degenerating muscle fibers begins in the upper legs and pelvis before spreading into the upper arms. Other symptoms include loss of some reflexes, a waddling gait, frequent falls and clumsiness (especially when running), difficulty when rising from a sitting or lying position or when climbing stairs, changes to overall posture, impaired breathing, lung weakness, and cardiomyopathy (heart muscle weakness that interferes with pumping ability). Many children are unable to run or jump. The wasting muscles, in particular the calf muscle (and, less commonly, muscles in the buttocks, shoulders, and arms), may be enlarged by an accumulation of fat and connective tissue, causing them to look larger and healthier than they actually are (called pseudohypertrophy). As the disease progresses, the muscles in the diaphragm that assist in breathing and coughing may weaken. Patients may experience breathing difficulties, respiratory infections, and swallowing problems. Bone thinning and scoliosis (curving of the spine) are common. Some children are mildly mentally impaired. Between ages 3 and 6, children may show brief periods of physical improvement followed by progressive muscle degeneration. Children with Duchenne MD are typically wheelchair-bound by age 12 and usually die in their late teens or early twenties from progressive weakness of the heart muscle, respiratory complications, or infection. 

Duchenne MD results from an absence of the muscle protein dystrophin. And blood tests of children with Duchenne MD show an abnormally high level of creatine kinase, which is apparent from birth. 

A rare, autosomal recessive form of MD is seen primarily in the Middle East and North Africa. The disease is clinically similar to Duchenne but is less severe and progresses more slowly. Onset of muscle weakness is typically between ages 5 and 10. Most patients lose the ability to walk in their early twenties, and most die in their forties from cardiac or respiratory complications. 

Becker MD is less severe than but closely related to Duchenne MD. Persons with Becker MD have partial but insufficient function of the protein dystrophin. The disorder usually appears around age 11 but may occur as late as age 25, and patients generally live into middle age or later. The rate of progressive, symmetric (on both sides of the body) muscle atrophy and weakness varies greatly among affected individuals. Many patients are able to walk until they are in their mid-thirties or later, while others are unable to walk past their teens. Some affected individuals never need to use a wheelchair. As in Duchenne MD, muscle weakness in Becker MD is typically noticed first in the upper arms and shoulders, upper legs, and pelvis. 

Early symptoms of Becker MD include walking on one's toes, frequent falls, and difficulty rising from the floor. Calf muscles may appear large and healthy as deteriorating muscle fibers are replaced by fat, and muscle activity may cause cramps in some people. Cardiac and mental impairments are not as severe as in Duchenne MD. 

Congenital MD refers to a group of autosomal recessive muscular dystrophies that are either present at birth or become evident before age 2. They affect both boys and girls. The degree and progression of muscle weakness and degeneration vary with the type of disorder. Weakness may be first noted when children fail to meet landmarks in motor function and muscle control. Muscle degeneration may be mild or severe and is restricted primarily to skeletal muscle. The majority of patients are unable to sit or stand without support, and some affected children may never learn to walk. There are three groups of congenital MD: 
- merosin-negative disorders, where the protein merosin (found in   the connective tissue that surrounds muscle fibers) is missing;   
- merosin-positive disorders, in which merosin is present but other needed   proteins are missing; and   
- neuronal migration disorders, in which very early in the development of   the fetal nervous system the migration of nerve cells (neurons) to their   proper location is disrupted. 

Defects in the protein merosin cause nearly half of all cases of congenital MD.

Patients with congenital MD may develop contractures (chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely), scoliosis, respiratory and swallowing difficulties, and foot deformities. Some patients have normal intellectual development while others become severely impaired. Weakness in diaphragm muscles may lead to respiratory failure. Congenital MD may also affect the central nervous system, causing vision and speech problems, seizures, and structural changes in the brain. Some children with the disorders die in infancy while others may live into adulthood with only minimal disability. 

Emery-Dreifuss MD primarily affects boys. The disorder has two forms: one is X-linked recessive and the other is autosomal dominant. 

Onset of Emery-Dreifuss MD is usually apparent by age 10, but symptoms can appear as late as the mid-twenties. This disease causes slow but progressive wasting of the upper arm and lower leg muscles and symmetric weakness. Contractures in the spine, ankles, knees, elbows, and back of the neck usually precede significant muscle weakness, which is less severe than in Duchenne MD. Contractures may cause elbows to become locked in a flexed position. The entire spine may become rigid as the disease progresses. Other symptoms include shoulder deterioration, toe-walking, and mild facial weakness. Serum creatine kinase levels may be moderately elevated. Nearly all Emery-Dreifuss MD patients have some form of heart problem by age 30, often requiring a pacemaker or other assistive device. Female carriers of the disorder often have cardiac complications without muscle weakness. Patients often die in mid-adulthood from progressive pulmonary or cardiac failure. 

Youth/adolescent-onset muscular dystrophies are classified two ways:

Facioscapulohumeral MD (FSHD) initially affects muscles of the face (facio), shoulders (scapulo), and upper arms (humera) with progressive weakness. Also known as Landouzy-Dejerine disease, this third most common form of MD is an autosomal dominant disorder. Life expectancy is normal, but some individuals become severely disabled. Disease progression is typically very slow, with intermittent spurts of rapid muscle deterioration. Onset is usually in the teenage years but may occur as late as age 40. Muscles around the eyes and mouth are often affected first, followed by weakness around the lower shoulders and chest. A particular pattern of muscle wasting causes the shoulders to appear to be slanted and the shoulder blades to appear winged. Muscles in the lower extremities may also become weakened. Reflexes are impaired only at the biceps and triceps. Changes in facial appearance may include the development of a crooked smile, a pouting look, flattened facial features, or a mask-like appearance. Some patients cannot pucker their lips or whistle and may have difficulty swallowing, chewing, or speaking. Other symptoms may include hearing loss (particularly at high frequencies) and lordosis, an abnormal swayback curve in the spine. Contractures are rare. Some FSHD patients feel severe pain in the affected limb. Cardiac muscles are not affected, and the pelvic girdle is rarely significantly involved. An infant-onset form of FSHD can also cause retinal disease and some hearing loss. 

Limb-girdle MD refers to more than a dozen inherited conditions marked by progressive loss of muscle bulk and symmetrical weakening of voluntary muscles, primarily those in the shoulders and around the hips. At least three forms of autosomal dominant limb-girdle MD (known as type 1) and eight forms of autosomal recessive limb-girdle MD (known as type 2) have been identified. Some autosomal recessive forms of the disorder are now known to be due to a deficiency of any of four dystrophin-glycoprotein complex proteins called the sarcoglycans. 

The recessive limb-girdle muscular dystrophies occur more frequently than the dominant forms, usually begin in childhood or the teenage years, and show dramatically increased levels of serum creatine kinase. The dominant limb-girdle muscular dystrophies usually begin in adulthood. In general, the earlier the clinical signs appear, the more rapid the rate of disease progression. Limb-girdle MD affects both males and females. Some forms of the disease progress rapidly, resulting in serious muscle damage and loss of the ability to walk, while others advance very slowly over many years and cause minimal disability, allowing a normal life expectancy. In some cases, the disorder appears to halt temporarily, but symptoms then resume. 

Weakness is typically noticed first around the hips before spreading to the shoulders, legs, and neck. Patients develop a waddling gait and have difficulty when rising from chairs, climbing stairs, or carrying heavy objects. Patients fall frequently and are unable to run. Contractures at the elbows and knees are rare but patients may develop contractures in the back muscles, which gives them the appearance of a rigid spine. Proximal reflexes (closest to the center of the body) are often impaired. Some patients also experience cardiomyopathy and respiratory complications. Intelligence remains normal. Most persons with limb-girdle MD become severely disabled within 20 years of disease onset. 

There are three forms of MD that usually begin in adulthood.

Distal MD, also called distal myopathy, describes a group of at least six specific muscle diseases that primarily affect distal muscles (those farthest away from the shoulders and hips) in the forearms, hands, lower legs, and feet. Distal dystrophies are typically less severe, progress more slowly, and involve fewer muscles than other forms of MD, although they can spread to other muscles. Distal MD can affect the heart and respiratory muscles, and patients may eventually require the use of a ventilator. Patients may not be able to perform fine hand movement and have difficulty extending the fingers. As leg muscles become affected, walking and climbing stairs become difficult and some patients may be unable to hop or stand on their heels. Onset of distal MD, which affects both men and women, is typically between the ages of 40 and 60 years. In one form of distal MD, a muscle membrane protein complex called dysferlin is known to be lacking. 

Although distal MD is primarily an autosomal dominant disorder, autosomal recessive forms have been reported in young adults. Symptoms are similar to those of Duchenne MD but with a different pattern of muscle damage. An infantile-onset form of autosomal recessive distal MD has also been reported. Slow but progressive weakness is often first noticed around age 1, when the child begins to walk, and continues to progress very slowly throughout adult life. 

Myotonic MD, also known as Steinert's disease and dystrophia myotonica, may be the most common adult form of MD. Myotonia, or an inability to relax muscles following a sudden contraction, is found only in this form of MD. People with myotonic MD can live a long life, with variable but slowly progressive disability. Typical disease onset is between ages 20 and 30, but it may develop earlier. Myotonic MD affects the central nervous system and other body systems, including the heart, adrenal glands and thyroid, eyes, and gastrointestinal tract. Muscles in the face and the front of the neck are usually first to show weakness and may produce a haggard, "hatchet" face and a thin, swan-like neck. Wasting and weakness noticeably affect forearm muscles. Other symptoms include cardiac complications, difficulty swallowing, droopy eyelids (called ptosis), cataracts, poor vision, early frontal baldness, weight loss, impotence, testicular atrophy, mild mental impairment, and increased sweating. Patients may also feel drowsy and have an excess need to sleep. 

This autosomal dominant disease affects both men and women. Females may have irregular menstrual periods and may be infertile. The disease occurs earlier and is more severe in successive generations. A childhood form of myotonic MD may become apparent between ages 5 and 10. Symptoms include general muscle weakness (particularly in the face and distal muscles), lack of muscle tone, and mental impairment. 

An expectant mother with myotonic MD can give birth to an infant with a rare congenital form of the disorder. Symptoms at birth may include difficulty swallowing or sucking, impaired breathing, absence of reflexes, skeletal deformities (such as club feet), and noticeable muscle weakness, especially in the face. Children with congenital myotonic MD may also experience mental impairment and delayed motor development. This severe infantile form of myotonic MD occurs almost exclusively in children who have inherited the defective gene from their mother, who may not know she is a carrier of the disease. 

The inherited gene defect that causes myotonic MD is an abnormally long repetition of a three-letter "word" in the genetic code. In unaffected people, the word is repeated a number of times, but in people with myotonic MD, it is repeated many more times. This triplet repeat gets longer with each successive generation. The triplet repeat mechanism has now been implicated in at least 15 other disorders, including Huntington's disease and the spinocerebellar ataxias. 

Oculopharyngeal MD (OPMD) generally begins in a person's forties or fifties and affects both men and women. In the United States, the disease is most common in families of French-Canadian descent and among Hispanic residents of northern New Mexico. Patients first report drooping eyelids, followed by weakness in the facial muscles and pharyngeal muscles in the throat, causing difficulty swallowing. The tongue may atrophy and changes to the voice may occur. Eyelids may droop so dramatically that some patients compensate by tilting back their heads. Patients may have double vision and problems with upper gaze, and others may have retinitis pigmentosa (progressive degeneration of the retina that affects night vision and peripheral vision) and cardiac irregularities. Muscle weakness and wasting in the neck and shoulder region is common. Limb muscles may also be affected. Persons with OPMD may find it difficult to walk, climb stairs, kneel, or bend. Those persons most severely affected will eventually lose the ability to walk. 
topHow are the muscular dystrophies diagnosed?
Both the patient's medical history and a complete family history should be thoroughly reviewed to determine if the muscle disease is secondary to a disease affecting other tissues or organs or is an inherited condition. It is also important to rule out any muscle weakness resulting from prior surgery, exposure to toxins, or current medications that may affect the patient's functional status. Thorough clinical and neurological exams can rule out disorders of the central and/or peripheral nervous systems, identify any patterns of muscle weakness and atrophy, test reflex responses and coordination, and look for contractions. 

Various laboratory tests may be used to confirm the diagnosis of MD.

Blood and urine tests can detect defective genes and help identify specific neuromuscular disorders. For example: 
- The level of serum aldolase, an enzyme involved in the breakdown of   glucose, is measured to confirm a diagnosis of skeletal muscle disease. High   levels of the enzyme, which is present in most body tissues, are noted in   patients with MD and some forms of myopathy.   
- Creatine kinase is an enzyme that leaks out of damaged muscle. Elevated   creatine kinase levels may indicate muscle damage, including some forms of MD,   before physical symptoms become apparent. Levels are significantly increased   in patients in the early stages of Duchenne and Becker MD. Testing can also   determine if a young woman is a carrier of the disorder.   
- Myoglobin is measured when injury or disease in skeletal muscle   is suspected. Myoglobin is an oxygen-binding protein found in cardiac and   skeletal muscle cells. High blood levels of myoglobin are found in patients   with MD.   
- Polymerase chain reaction (PCR) can detect mutations in the dystrophin   gene. Also known as molecular diagnosis or genetic testing, PCR is a method   for generating and analyzing multiple copies of a fragment of DNA.   
- Serum electrophoresis is a test to determine quantities of various   proteins in a person's DNA. A blood sample is placed on specially treated   paper and exposed to an electric current. The charge forces the different   proteins to form bands that indicate the relative proportion of each protein   fragment. 

Electron microscopy can identify changes in subcellular components of muscle fibers. Electron microscopy can also identify changes that characterize cell death, mutations in muscle cell mitochondria, and an increase in connective tissue seen in muscle diseases such as MD. Changes in muscle fibers that are evident in a rare form of distal MD can be seen using an electron microscope. 

Exercise tests can detect elevated rates of certain chemicals following exercise and are used to determine the nature of the MD or other muscle disorder. Some exercise tests can be performed at the patient's bedside while others are done at clinics or other sites using sophisticated equipment. These tests also assess muscle strength. They are performed when the patient is relaxed and in the proper position to allow technicians to measure muscle function against gravity and detect even slight muscle weakness. If weakness in respiratory muscles is suspected, respiratory capacity may be measured by having the patient take a deep breath and count slowly while exhaling. 

Genetic testing looks for genes known to either cause or be associated with inherited muscle disease. DNA analysis and enzyme assays can confirm the diagnosis of certain neuromuscular diseases, including MD. Genetic linkage studies can identify whether a specific genetic marker on a chromosome and a disease are inherited together. They are particularly useful in studying families with members in different generations who are affected. An exact molecular diagnosis is necessary for some of the treatment strategies that are currently being developed. 

Genetic counseling can help parents who have a family history of MD determine if they are carrying one of the mutated genes that cause the disorder. Two tests can be used to help expectant parents find out if their child is affected. 
- Amniocentesis, done usually at 14-16 weeks of pregnancy, tests a   sample of the amniotic fluid in the womb for genetic defects (the fluid and   the fetus have the same DNA). Under local anesthesia, a thin needle is   inserted through the woman's abdomen and into the womb. About 20 milliliters   of fluid (roughly 4 teaspoons) is withdrawn and sent to a lab for evaluation.   Test results often take 1-2 weeks.   
- Chorionic villus sampling, or CVS, involves the removal and   testing of a very small sample of the placenta during early pregnancy. The   sample, which contains the same DNA as the fetus, is removed by catheter or a   fine needle inserted through the cervix or by a fine needle inserted through   the abdomen. The tissue is tested for genetic changes identified in an   affected family member. Results are usually available within 2 weeks. 

Magnetic resonance imaging (MRI) is used to examine muscle quality, any atrophy or abnormalities in size, and fatty replacement of muscle tissue, as well as to monitor disease progression. MRI scanning equipment creates a strong magnetic field around the body. Radio waves are then passed through the body to trigger a resonance signal that can be detected at different angles within the body. A computer processes this resonance into either a three-dimensional picture or a two-dimensional "slice" of the tissue being scanned. MRI is a noninvasive, painless procedure. Other forms of diagnostic imaging for MD include phosphorus magnetic resonance spectroscopy, which measures cellular response to exercise and the amount of energy available to muscle fiber, and ultrasound imaging (also known as sonography), which uses high-frequency sound waves to obtain images inside the body. The sound wave echoes are recorded and displayed on a computer screen as a real-time visual image. Ultrasound may be used to measure muscle bulk. 

Muscle biopsies are used to monitor the course of disease and treatment effectiveness. Using a local anesthetic, a small sample of muscle is removed and studied under a microscope. The sample may be gathered either surgically, through a slit made in the skin, or by needle biopsy, in which a thin hollow needle is inserted through the skin and into the muscle. A small piece of muscle remains in the hollow needle when it is removed from the body. The muscle specimen is stained and examined to determine whether the patient has muscle disease, nerve disease (neuropathy), inflammation, or another myopathy. Muscle biopsies also assist in carrier testing. With the advent of accurate molecular techniques, muscle biopsy is no longer essential for diagnosis. 

Immunofluorescence testing can detect specific proteins such as dystrophin within muscle fibers. Following biopsy, fluorescent markers are used to stain the sample that has the protein of interest. 

Neurophysiology studies can identify physical and/or chemical changes in the nervous system. 
- Electromyography (EMG) can record muscle fiber and motor unit   activity. A tiny needle containing an electrode is inserted through the skin   into the muscle. The electrical activity detected in the muscle can be   displayed either in printout form or on a monitor, and can also be heard when   played through a speaker. Results may reveal electrical activity   characteristic of MD. Each electrode displays an average of that muscle's   activity. Several electrodes may be needed to display activity in large   skeletal muscles.   
- Nerve conduction velocity studies measure the speed with which an   electrical signal travels along a nerve. A small electrode sends a signal to a   receiving electrode placed elsewhere along the nerve. The length of the nerve   between the electrodes is divided by the time needed for the signal to travel   between them. The response can be used to determine any nerve damage.   
- Repetitive stimulation studies involve electrically stimulating a nerve 5   to 10 times, at a frequency of 2-3 shocks per second, to study muscle   function. A mild shock is sent via electrodes that are taped to the skin on   top of the muscle(s) to be tested and the response is displayed on an   oscilloscope, an instrument used to examine electrical signals. A nerve is   then stimulated at another site to evaluate electrical activity down the   nerve, across the neuromuscular junction, and into the muscle. 
topHow are the muscular dystrophies treated?
There is no specific treatment that can stop or reverse the progression of any form of MD. All forms of MD are genetic and cannot be prevented. Treatment is aimed at keeping the patient independent for as long as possible and preventing complications that result from weakness, reduced mobility, and cardiac and respiratory difficulties. Treatment may involve a combination of approaches, including physical therapy, drug therapy, and surgery. 

Assisted ventilation is often needed to treat respiratory muscle weakness that accompanies many forms of MD, especially in the later stages. Oxygen is fed through a flexible mask (or, in some cases, a tube inserted through the esophagus and into the lungs) to help the lungs inflate fully. Since respiratory difficulty may be most extreme at night, some patients may need overnight ventilation. A mask worn over the face is connected by tube to a machine that puts out intermittent bursts of forced oxygen. Obese patients with Duchenne MD may develop obstructive sleep apnea and require nighttime ventilation. Patients on a ventilator may also require the use of a gastric feeding tube. 

Drug therapy may be prescribed to delay muscle degeneration. Corticosteroids such as prednisone can slow the rate of muscle deterioration in Duchenne MD and help children retain strength and prolong independent walking by as much as several years. However, these medicines have side effects such as weight gain and bone fragility that can be especially troubling in children. Immunosuppressive drugs such as cyclosporin and azathioprine can delay some damage to dying muscle cells. Drugs that may provide short-term relief from myotonia (muscle spasms and weakness) include mexiletine; phenytoin; baclofen, which blocks signals sent from the spinal cord to contract the muscles; dantrolene, which interferes with the process of muscle contraction; and quinine. (Drugs for myotonia are not effective in myotonic MD but work well for myotonia congenita, a genetic neuromuscular disorder characterized by the slow relaxation of the muscles.) Anticonvulsants, also known as antiepileptics, are used to control seizures and some muscle activity. Commonly prescribed oral anticonvulsants include carbamazepine, phenytoin, clonazepam, gabapentin, topiramate, and felbamate. Respiratory infections may be treated with antibiotics. 

Physical therapy can help prevent deformities, improve movement, and keep muscles as flexible and strong as possible. Options include passive stretching, postural correction, and exercise. A program is developed to meet the individual patient's needs. Therapy should begin as soon as possible following diagnosis, before there is joint or muscle tightness. 
- Passive stretching can increase joint flexibility and prevent contractures   that restrict movement and cause loss of function. When done correctly,   passive stretching is not painful. The therapist or other trained health   professional slowly moves the joint as far as possible and maintains the   position for about 30 seconds. The movement is repeated several times during   the session. Passive stretching on children may be easier following a warm   bath or shower.   
- Regular, moderate exercise can help MD patients maintain range of motion   and muscle strength, prevent muscle atrophy, and delay the development of   contractures. Persons with a weakened diaphragm can learn coughing and deep   breathing exercises that are designed to keep the lungs fully expanded.   
- Postural correction is used to counter the muscle weakness, contractures,   and spinal irregularities that force MD patients into uncomfortable positions.   When possible, patients should sit upright, with feet at a 90-degree angle to   the floor. Pillows and foam wedges can help keep the person upright,   distribute weight evenly, and cause the legs to straighten. Armrests should be   at the proper height to provide support and prevent leaning.   
- Support aids such as wheelchairs, splints and braces, other orthopedic   appliances, and overhead bed bars (trapezes) can help maintain mobility.   Braces are used to help stretch muscles and provide support while keeping the   patient ambulatory. Spinal supports can help delay scoliosis. Night splints,   when used in conjunction with passive stretching, can delay contractures.   Orthotic devices such as standing frames and swivel walkers help patients   remain standing or walking for as long as possible, which promotes better   circulation and improves calcium retention in bones.   
- Repeated low-frequency bursts of electrical stimulation to the thigh   muscles can produce a slight increase in strength in boys with Duchenne MD.   
- Speech therapy may help patients whose facial and throat muscles have   weakened. Patients can learn to use special communication devices, such as a   computer with voice synthesizer.   
- Special exercises, or a special diet and feeding techniques, can help MD   patients who have a swallowing disorder. Some patients may find it difficult   to pass food or liquid from the mouth to the stomach, which can lead to poor   nutrition and increased susceptibility to infection. 

Dietary changes have not been shown to slow the progression of MD. Proper nutrition is essential, however, for overall health. Limited mobility or inactivity resulting from muscle weakness can contribute to obesity, dehydration, and constipation. A high-fiber, high-protein, low-calorie diet combined with recommended fluid intake may help. MD patients with swallowing or breathing disorders and those persons who have lost the ability to walk independently should be monitored for signs of malnutrition. 

Occupational therapy may help some patients deal with progressive weakness and loss of mobility. Some individuals may need to learn new job skills or new ways to perform tasks while other persons may need to change jobs. Assistive technology may include modifications to home and workplace settings and the use of motorized wheelchairs, wheelchair accessories, and adaptive utensils. 

Corrective surgery is often performed to ease complications from MD. 
- Tendon or muscle-release surgery is recommended when a contracture becomes   severe enough to lock a joint or greatly impair movement. The procedure, which   involves severing a tendon or muscle to free movement, is usually performed   under general anesthesia. Unfortunately, lengthening a muscle or tendon makes   it weaker. Rehabilitation includes the use of braces and physical therapy to   strengthen muscles and maintain the restored range of motion.   
- Patients with either Emery-Dreifuss or myotonic MD may eventually require   a pacemaker to treat cardiac problems.   
- Surgery to reduce the pain and postural imbalance caused by scoliosis may   help some patients. Scoliosis occurs when the muscles that support the spine   begin to weaken and can no longer keep the spine straight. The spinal curve,   if too great, can interfere with breathing and posture, causing pain. One or   more metal rods may need to be attached to the spine to increase strength and   improve posture. Another option is spinal fusion, in which bone is inserted   between the vertebrae in the spine and allowed to grow, fusing the vertebrae   together to increase spinal stability.   
- Persons with myotonic MD often develop cataracts, a clouding of the lens   of the eye that blocks light. Cataract surgery involves removing the cloudy   lens to improve the person's ability to see. 
topWhat is the prognosis?
The prognosis varies according to the type of MD and the speed of progression. Some types are mild and progress very slowly, allowing normal life expectancy, while others are more severe and result in functional disability and loss of ambulation. Life expectancy may depend on the degree of muscle weakness and any respiratory and/or cardiac complications. 
topWhat research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) supports a broad program of research on MD. The goals of these studies are to increase understanding of MD and its causes, develop better therapies, and, ultimately, find ways to prevent and cure it. The NINDS and its sister institutes, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute of Child Health and Human Development (NICHD), lead the MD research efforts conducted at the National Institutes of Health (NIH) or at grantee institutions throughout the country. 

Drug-based therapy to delay muscle wastingProgressive loss of muscle mass is primarily responsible for reduced quality and length of life in MD. In the absence of a genetic cure, drug treatment strategies designed to slow this muscle degeneration can have substantial impact on quality of life. 

Corticosteroids are known to extend the ability of Duchenne MD patients to walk by up to 2 years, but steroids have substantial side effects and their mechanism of action is unknown. NIH-funded scientists have established clinical standards for steroid treatment of Duchenne MD. A recent study identified one mechanism of steroid action, raising the prospect that a modified steroid may be designed to minimize or eliminate side effects. 

Researchers at the NINDS and several universities are exploring the potential of using agents that inhibit enzymes that degrade muscle as a treatment for various types of MD. 

Scientists are also exploring several other drugs that may help delay the loss of muscle mass:
- The drugs albuterol and oxandrolone, either alone or in combination, are   being studied to determine if they are able to increase strength and muscle   mass in patients with FSHD. The study will also determine if albuterol given   in "pulsed" fashion (controlled drug release) has more effect than when given   continuously.   
- The nutritional supplement Coenzyme Q10 has been found to protect cell   membranes from oxidative injury. It may also be essential for proper   mitochondrial function and cellular energy production. Scientists are   investigating the safety and efficacy of Coenzyme Q10 when added to steroids   as a treatment for boys with Duchenne MD.   
- The drug mexiletine is being studied for effectiveness in reducing   myotonia and improving muscle function in patients with myotonic MD.   
- The protein creatine, which is produced naturally and is also absorbed   through food intake, has been shown in animal models to increase energy in   nerve cells and improve muscle strength. Persons who show symptoms of MD and   other neuromuscular diseases generally have low creatine kinase levels.   Creatine may help prevent the loss of mitochondria components within cells   that break down other intercellular material and produce energy. Studies in   humans are examining the protein's effect on mitochondria and are identifying   optimal dosage levels.   
- Oxatomide, a steroid that interferes with the release of histamine from   mast cells (involved with inflammatory diseases), is being clinically tested   for safety and efficacy in increasing strength among boys with Duchenne MD.   Participants will have their strength tested monthly for 6 months.   
- Using the mdx mouse model for Duchenne MD, scientists are   evaluating the combination of glutamine and creatine monohydrate as a possible   therapy. Glutamine, an amino acid, is essential for muscle strength.   (Additional animal models for Duchenne MD include other strains of mice and   the xmd golden retriever.) 

Enhancing natural muscle repair mechanismsSkeletal muscle has the ability to repair itself, but its regeneration and repair mechanisms are progressively depleted during the course of several types of MD. Understanding the repair mechanisms may provide new therapies to slow, and possibly stabilize, muscle degeneration. 

NIH-supported studies have provided a broad understanding of the mechanisms of muscle regeneration. Additional NIH-funded studies are identifying points in the regeneration-repair pathways that can be targeted by either drug or gene therapy for muscle rescue. For example, researchers have shown that chronic blockade of the muscle growth inhibitor myostatin can enhance muscle repair in animal models of MD. Other NIH-funded investigators have found that increased expression of a muscle repair protein, dysferlin, can help offset muscle damage in dystrophic animals. And the strategy of enhancing natural muscle repair mechanisms with insulin-like growth factor 2 is being used in a clinical trial for myotonic dystrophy. If effective, this approach is translatable to other types of MD. 

Cell-based therapyThe muscle cells of MD patients often lack a critical protein, such as dystrophin in Duchenne MD or sarcoglycan in the limb-girdle MDs. Scientists are exploring the possibility that the missing protein can be replaced by introducing muscle stem cells capable of making the missing protein in new muscle cells. Such new cells would be protected from the progressive degeneration characteristic of MD and potentially restore muscle function in affected persons. 

The natural regenerative capacity of muscle provides possibilities for treatment of MD. Attempts to take muscle precursor cells from fathers of Duchenne patients and implant them into patients' muscles originally failed. However, more recent studies have focused on using stem cells to try to restore missing proteins in MD patients. Researchers have shown that stem cells can be used to deliver a functional dystrophin gene to skeletal muscles of dystrophic mice. 

Gene replacement therapyA true cure for Duchenne, congenital, and limb-girdle MD might be obtained if the defective dystrophin gene could be replaced by a functional gene. The large size of the dystrophin gene and the early inability of gene-delivery systems (viral vectors) to target muscle have been substantive barriers to development of gene therapy for Duchenne MD. 

Over the last several years, a mini-dystrophin gene (one that is small enough for a viral carrier to deliver it) has proven successful in animal models of Duchenne MD. Viral delivery systems are much better today than they once were (viral vector delivery can set off a serious immune response). As a result, NIH-funded researchers have made important progress in delivering a dystrophin mini-gene to muscles of a mouse model of Duchenne MD. 

Scientists also are using high-throughput screening (HTS) to find drugs that increase the muscle production of the protein utrophin, which is similar to dystrophin and can help compensate for its loss. HTS lets scientists test hundreds of chemical compounds quickly to find leads for further drug development. 

Genetic modification therapy to bypass inherited mutationsApproximately 80 percent of Duchenne MD patients have mutations in the dystrophin gene that causes it to function improperly and stop producing the dystrophin protein. By manipulating the protein synthesis process, production of a gene that "reads through" the genetic mutation that stops production can result in functional dystrophin. 

Two strategies are currently under study to bypass dystrophin mutations. First, the antibiotic gentamicin has been shown to be effective in causing the synthesis machinery to ignore the premature stop signal and produce functional dystrophin. This strategy may be useful in about 15 percent of Duchenne MD patients. An NINDS-funded clinical trial using gentamicin in Duchenne MD patients is under way. Second, a more recent approach uses splicing technology to skip past the mutations in the dystrophin gene to a point where the genetic information is complete and can produce a functional protein. This strategy has shown promise in a mouse model of Duchenne MD. As many as 80 percent of patients could benefit from this new technology. 

Moving forward with research in MDMany of the strategies for developing new therapies are directed toward Duchenne MD, since it is the best understood MD at the moment. Progress in treatment for Duchenne MD may, however, have application for other types of MD. The NIH has recently undertaken several new initiatives in training, career development, and research that are targeted toward MD. These advances, along with the NINDS focus on translational and clinical research, will lead to the growth of clinical trials and promising treatment strategies. 

The NINDS and the NIAMS fund a research registry for FSHD and myotonic MD. This national registry serves as a resource for scientists seeking a cure for these diseases, in addition to enhancing research on what changes occur in MD. The registry, based at the University of Rochester in New York, recruits patients and stores medical and family history data for individuals with clinically diagnosed FSHD and myotonic MD. Scientists have access to statistical analyses of the registry data and to registry members who have agreed to assist with particular research studies. Similar registries for Duchenne MD are supported by the Centers for Disease Control and Prevention. 

The MD CARE Act and the federal commitment to muscular dystrophyIn December 2001, President George W. Bush signed into law the Muscular Dystrophy Community Assistance, Research, and Education Amendments Act of 2001 (the MD CARE Act, Public Law 107-84). As part of the Act, the NIH is expanding and intensifying its research efforts on the muscular dystrophies and has established the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers of Excellence to promote basic and clinical research on these disorders. The Act also authorized the Centers for Disease Control and Prevention to award grants for epidemiologic studies and data collection. Other federal agencies contribute to this research initiative. 

In response to the MD CARE Act, the NIH formed the Muscular Dystrophy Coordinating Committee to help guide research on MD. The MD Coordinating Committee is made up of physicians, scientists, NIH professional staff, and representatives of other federal agencies and voluntary health organizations with a focus on MD. The purpose of the group is to help NIH add new capabilities to the national effort to understand and treat MD, without duplicating existing programs. The MD Coordinating Committee has developed a broad research and education plan and continues to refine the plan to improve basic, translational, and clinical research in MD, with the goal of improving the quality of life for patients with MD. Information about the committee and plan is available at http://www.ninds.nih.gov/find_people/groups/mdcc/. 

Past research has led to the discovery of disease mechanisms and improved treatment for many forms of MD. Current research promises to generate further improvements. In the coming years, physicians and patients can look forward to new forms of therapy developed through an understanding of the unique traits of MD. 
topWhere can I get more information?
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at: 

BRAINP.O. Box 5801Bethesda, MD 20824(800) 352-9424http://www.ninds.nih.gov/

Information also is available from the following organizations:
Facioscapulohumeral Muscular Dystrophy (FSH)       Society64 Grove StreetWatertown, MA   02472info@fshsociety.orghttp://www.fshsociety.org/Tel:       781-275-7781 617-658-7878Fax: 781-860-0599Facilitates support       groups, publishes a newsletter, organizes conferences and meetings, and       awards research grants towards the prevention, cause and treatment of       FacioScapuloHumeral muscular dystrophy worldwide. Provides public       awareness of FSHD by providing information, referrals, education, and       advocacy programs and services. Promotes collaborative research and       collects and disseminates research information.Muscular Dystrophy Association3300       East Sunrise DriveTucson, AZ   85718-3208mda@mdausa.orghttp://www.mda.org/Tel: 520-529-2000       800-572-1717Fax: 520-529-5300Voluntary health agency that fosters       neuromuscular disease research and provides patient care funded almost       entirely by individual private contributors. MDA addresses the muscular       dystrophies, spinal muscular atrophy, ALS, Charcot-Marie-Tooth disease,       myasthenia gravis, Friedreich's ataxia, metabolic diseases of muscle, and       inflammatory diseases of muscle, for a total of more than 40 neuromuscular       diseases.Muscular Dystrophy Family       Foundation7220 U.S. 31 SouthIndianapolis, IN         46227mdff@mdff.orghttp://www.mdff.org/Tel: 317-923-6333       800-544-1213Fax: 317-923-6334Provides services, resources,       adaptive equipment, and home medical equipment to individuals with       muscular dystrophy and their families to improve independence and quality       of life. Focuses on meeting the day-to-day needs of individuals and       families.Parent Project Muscular Dystrophy       (PPMD)158 Linwood PlazaSuite 220Fort Lee, NJ         07024info@parentprojectmd.orghttp://www.parentprojectmd.org/Tel:       201-944-9985 800-714-KIDS (5437)Fax: 201-944-9987PPMD is a       parent-led organization dedicated to encouraging efforts to expedite       treatments for DMD/BMD while improving quality of life for the boys       affected.International Myotonic Dystrophy       OrganizationP.O. Box 1121Sunland, CA         91041-1121info@myotonicdystrophy.orghttp://www.myotonicdystrophy.org/Tel:       818-951-2311 866-679-7954International foundation dedicated to       improved management and treatment of Myotonic Dystrophy. Supports patients       with information and services worldwide.National Institute of Arthritis and Musculoskeletal       and Skin Diseases (NIAMS)National Institutes of Health,       DHHS31 Center Dr., Rm. 4C02 MSC 2350Bethesda, MD         20892-2350NIAMSinfo@mail.nih.govhttp://www.niams.nih.gov/Tel:       301-496-8190 877-22-NIAMS (226-4267)National Institute of Child Health and Human       Development (NICHD)National Institutes of Health, DHHS31       Center Drive, Rm. 2A32 MSC 2425Bethesda, MD   20892-2425http://www.nichd.nih.gov/Tel:       301-496-5133Fax: 301-496-7101Centers for Disease Control and Prevention       (CDCP)U.S. Department of Health and Human Services1600       Clifton Road, N.E.Atlanta, GA   30333inquiry@cdc.govhttp://www.cdc.gov/Tel: 800-311-3435       404-639-3311/404-639-3543top
Glossary

amniocentesis - a process of prenatal genetic analysis that uses a sample of the amniotic fluid taken from the womb. 

atrophy - a decrease in size or wasting away of a body part or tissue. 

autosomal dominant - a pattern of inheritance in which a child acquires a disease by receiving a normal gene from one parent and a defective gene from the other parent. 

autosomal recessive - a pattern of inheritance in which both parents carry and pass on a defective gene to their child. 

biopsy - a procedure in which tissue or other material is removed from the body and studied for signs of disease. 

cardiomyopathy - heart muscle weakness that interferes with the heart's ability to pump blood. 

carrier - an individual who doesn't have a disease but has one normal gene and one gene for a genetic disorder and is therefore capable of passing this disease to her or his children. 

chorionic villus sampling - a prenatal genetic test that involves removal and examination of a piece of the placenta. 

chromosomes - genetic structures that contains DNA. 

contracture - chronic shortening of a muscle or tendon that limits movement of a bony joint, such as the elbow. 

creatine kinase - a protein needed for the chemical reactions that produce energy for muscle contractions; high levels in the blood indicate muscle damage. 

dystrophin - a protein that helps maintain the shape and structure of muscle fibers. 

electromyography - a recording and study of the electrical properties of skeletal muscle. 

glycoprotein - a molecule that has a protein and a carbohydrate component. 

linkage studies - tests conducted among family members to determine how a genetic trait is passed on through generations. 

lordosis - an abnormal forward curving of the spine. 

merosin - a protein found in the connective tissue that surrounds muscle fibers. 

myoglobin - an oxygen-binding protein in muscle cells that generates energy by turning glucose into carbon dioxide and water. 

myopathy - any disorder of muscle tissue or muscles. 

myotonia - an inability to relax muscles following a sudden contraction. 

phagocytosis - a process in which material is taken into the cell and digested. 

pseudohypertrophy -a condition in which muscles may be enlarged by an accumulation of fat and connective tissue, causing them to look larger and healthier than they actually are. 

ptosis - an abnormal drooping of the eyelids. 

scoliosis - an abnormal lateral, or sideways, curving of the spine. 

X-linked recessive - a pattern of disease inheritance in which the mother carries the affected gene on the chromosome that determines the child's sex and passes it to her son. 
top"Muscular Dystrophy: Hope Through Research," NINDS. 
Back to Muscular Dystrophy Information Page 

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Prepared by:Office of Communications and Public LiaisonNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda, MD 20892 

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history. 

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated December 18, 2009

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