Duchenne muscular dystrophy (also known as pseudohypertrophic muscular dystrophy or muscular dystrophy - Duchenne type) is an inherited disorder characterized by rapidly progressive muscle weakness which starts in the legs and pelvis and later affects the whole body. Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy. It usually affects only boys, but in rare cases it can also affect girls. It is an X-linked recessive inherited disease.

It is named after the French neurologist Guillaume Benjamin Amand Duchenne. One third of the cases are known to be caused by development of spontaneous mutations in the dystrophin gene, while the remainder are inherited. Boys with DMD develop weak muscles because the muscle fibers that were present at birth are destroyed. It is due to mutations in the dystrophin gene, which encodes a cell membrane protein in myocytes (muscle cells).

Contents

1 Onset 2 Genetics 3 Symptoms 4 Signs and tests 5 Treatment 5.1 Support Groups 5.2 Expectations (prognosis) 5.3 Physiotherapy 5.4 Mechanical Ventilatory Assistance: Volume Ventilators 6 Complications 7 Prevention

Onset

Symptoms usually appear in males 1 to 6 years old. By age 10, braces may be required for walking, and by age 12, most patients are confined to a wheelchair. Bones may develop abnormally, causing skeletal deformities of the spine and other areas due to contractures. Muscular weakness and skeletal deformities contribute to frequent breathing disorders. Cardiomyopathy occurs in almost all cases. Intellectual impairment occurs in approximately 30% of Duchenne's patients, but does not worsen as the disorder progresses. Duchenne muscular dystrophy occurs in approximately 1 out of 3,500 males. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy. A mother carrying the Duchenne gene has a 50% change of passing the disease on to any male children.

In contrast, Becker muscular dystrophy is a form that progresses much more slowly.

Genetics

Duchenne dystrophy is a type of dystrophinopathy which includes a spectrum of muscle disease caused by mutations in the DMD gene, which encodes the protein dystrophin. Becker's muscular dystrophy is a milder type of dystrophinopathy. Although it is caused by a defective gene, it often occurs in people from families without a known family history of the condition.

Duchenne muscular dystrophy is inherited in an X-linked recessive pattern. This means that women are almost never affected; women normally have two X chromosomes, one of which contains a normal, dominant copy of the gene that will make enough of the protein for them to avoid symptoms. Women who carry the defective gene can pass an abnormal X on to their sons, however. Since boys have an X from their mother and a Y from father, there is no second X to make up for the defective gene from the carrier mother. The sons of carrier females each have a 50% chance of having the disease, and the daughters each have a 50% chance of being carriers.

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

Symptoms

• Muscle weakness
• Rapidly progressive
• Frequent falls
• Difficulty with motor skills (running, hopping, jumping)
• Progressive difficulty walking
• Ability to walk may be lost by age 12
• Fatigue
• Intellectual impairment (in approx. 30% of Duchenne's patients)
• Skeletal deformities
• Chest and back (scoliosis)
• Muscle deformities
• Contractures of heels, legs
• Pseudohypertrophy of calf muscles

Symptoms usually appear before age 6 and may appear as early as infancy. There is progressive muscle weakness of the legs and pelvis, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body. Calf muscles initially enlarge -- the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy). Muscle contractures occur in the legs, rendering the muscles unusable because the muscle fibers shorten and fibrosis occurs in connective tissue.

Signs and tests

Muscle wasting (atrophy) begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy is commonly present, but signs of congestive heart failure or arrhythmias (irregular heartbeats) are rare. Respiratory disorders are common during the later stages, including pneumonia and aspiration of food or fluid into the lungs.

• A serum CPK is highly elevated.
• A neurologic exam demonstrates weaness and lack of coordination or balance.
• An EMG (electromyography) shows that weakness is caused by destruction of muscle tissue rather than nerve damage.
• Genetic testing
• A muscle biopsy.

DMD may be suspected in generalised muscular weakness in a child. Many display the Gower sign: to get up from sitting on the floor, they support their back muscles by putting their hands on their knees and thighs.

Increased creatine kinase levels may be an indication of increased muscle breakdown. The formal diagnosis is made on biopsy of the muscle and DNA sequencing of the dystrophin gene.

Molecular genetic testing of the DMD gene is available clinically and can establish the diagnosis of a dystrophinopathy without muscle biopsy in the majority of cases of DMD and BMD. In the remaining cases of DMD, BMD, and DMD-related dilated cardiomyopathy, a combination of clinical findings, family history, serum CK concentration, and muscle biopsy with dystrophin studies confirms the diagnosis. Virtually all males with DMD and at least 85% of males with BMD have identifiable DMD gene mutations.

Treatment

There is no known cure for Duchenne muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life. Activity is encouraged. Inactivity (such as bed rest) can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength and function. Orthopaedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care.

Support Groups

Joining a support group where members share common experiences and problems can often help relieve the stress of this illness. See muscular dystrophy - support group. The Muscular Dystrophy Association is an excellent source of information on this disease.

Expectations (prognosis)

Duchenne muscular dystrophy results in rapidly progressive disability. Death usually occurs by age 25, typically from respiratory (lung) disorders.

Physiotherapy

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

• minimise the development of contractures and deformity by developing a programme of stretches and exercises where appropriate
• anticipate and minimise other secondary complications of a physical nature
• prescribe equipment such as orthoses, callipers, wheelchairs and standing frames
• advise on moving and handling issues and equipment
• monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

Mechanical Ventilatory Assistance: Volume Ventilators

Modern "volume ventilators," which deliver a preset volume (amount) of air to the child with each breath, are valuable in the treatment of children with muscular dystrophy related respiratory problems.

When the vital capacity has dropped below 40 percent of normal, a volume ventilator may be used during sleeping hours, a time when the child is most likely to be underventilating ("hypoventilating"). Hypoventilation during sleep is determined by a thorough history of sleep disorder with an oximetry study and a capillary blood gas (See Pulmonary Function Testing). The ventilator requires a nasal or facemask for connection to the airway. The masks are constructed of comfortable plastic with Velcro straps to hold them in place during sleep.

As the vital capacity declines to less than 30 percent of normal, a volume ventilator may also be needed during the day for more assistance. The child gradually will increase the amount of time using the ventilator during the day as needed. A mouthpiece can be used in the daytime and a nasal or facemask can be used during sleep. The machine can easily fit on a ventilator tray on the bottom of a power wheelchair.

There may be times such as during a respiratory infection when a child needs to rest his/her respiratory muscles during the day even when not yet using full-time ventilation. The versatility of the volume ventilator can meet this need, allowing tired breathing muscles to rest and also allowing aerosol medications to be delivered.

Complications

• Deformities
• Permanent, progressive disability
• Decreased mobility
• Decreased ability for self-care
• Mental impairment (varies, usually minimal)
• Pneumonia or other respiratory infections
• Respiratory failure
• Cardiomyopathy
• Congestive heart failure (rare)
• Heart arrhythmias (rare)
• Calling your health care provider
• Call your health care provider if symptoms indicate Duchenne muscular dystrophy.

Prevention

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