Duchenne Muscular Dystrophy (DMD)

Pseudohypertrophic muscular dystrophy; Muscular dystrophy - Duchenne type

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty walking, breathing, and death. The incidence is 1 in 3,000.

Females and males are affected, though females are rarely affected and are more often carriers. The disorder is caused by a mutation in the dystrophin gene, located in humans on the X chromosome (Xp21).

The dystrophin gene codes for the protein dystrophin, an important structural component within muscle tissue. Dystrophin provides structural stability to the dystroglycan complex (DGC), located on the cell membrane.

Symptoms usually appear in male children before age 5 and may be visible in early infancy. Progressive proximal muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed first.

 Eventually this weakness spreads to the arms, neck, and other areas. Early signs may include pseudohypertrophy (enlargement of calf and deltoid muscles), low endurance, and difficulties in standing unaided or inability to ascend staircases. As the condition progresses, muscle tissue experiences wasting and is eventually replaced by fat and fibrotic tissue (fibrosis). By age 10, braces may be required to aid in walking but most patients are wheelchair dependent by age 12.

Later symptoms may include abnormal bone development that lead to skeletal deformities, including curvature of the spine. Due to progressive deterioration of muscle, loss of movement occurs, eventually leading to paralysis. Intellectual impairment may or may not be present but if present, does not progressively worsen as the child ages.

The average life expectancy for patients afflicted with DMD varies from late teens to early to mid 20s. There have been reports of a few DMD patients surviving to the age of 40, but this is extremely rare.

Duchenne muscular dystrophy is an inherited disorder that involves rapidly worsening muscle weakness.

Causes, incidence, and risk factors

Duchenne muscular dystrophy is a rapidly-worsening form of muscular dystrophy. Other muscular dystrophies (including Becker's muscular dystrophy) get worse much more slowly.

US President Barack Obama met Dusty Brandom, 18,
at the White House in Washington, D.C., recently.
Obama jokingly said that he would love to join the
expedition to climb Mount Kinabalu. Brandon one the
boys who affected by Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition.

Because of the way the disease is inherited, males are more likely to develop symptoms than are women. The sons of females who are carriers of the disease (women with a defective gene but no symptoms themselves) each have a 50% chance of having the disease. The daughters each have a 50% chance of being carriers.

Duchenne muscular dystrophy occurs in approximately 1 out of every 3,600 male infants. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy.

Symptoms

Symptoms usually appear before age 6 and may appear as early as infancy. They may include:

• Fatigue
• Mental retardation (possible, but does not worsen over time)
• Muscle weakness
  
  • Begins in the legs and pelvis, but also occurs less severely in the arms, neck, and other areas of the body
  • Difficulty with motor skills (running, hopping, jumping)
  • Frequent falls
  • Rapidly worsening weakness
• Progressive difficulty walking
  
  • Ability to walk may be lost by age 12

By age 10, the person may need braces for walking. By age 12, most patients are confined to a wheelchair.

Signs and tests

A complete nervous system (neurological), heart, lung, and muscle exam may show:

• Abnormal heart muscle (cardiomyopathy)
• Congestive heart failure or irregular heart rhythm (arrhythmias) -- rare
• Deformities of the chest and back (scoliosis)
• Enlarged calf muscles, which are eventually replaced by fat and connective tissue (pseudohypertrophy)
• Loss of muscle mass (wasting)
• Muscle contractures in the heels, legs
• Muscle deformities
• Respiratory disorders, including pneumonia and aspiration of food or fluid into the lungs (in late stages of the disease)

Tests may include:

• Electromyography (EMG)
• Genetic tests
• Muscle biopsy
• Serum CPK

Treatment

There is no known cure for Duchenne muscular dystrophy. Treatment aims to control symptoms to maximize quality of life. Gene therapy may become available in the future.

Activity is encouraged. Inactivity (such as bedrest) can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength and function. Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability to care for yourself.

There is no current cure for DMD, although phase 1-2a trials with exon-skipping treatment for certain mutations have halted decline and produced small clinical improvements in walking.

Treatment is generally aimed at controlling the onset of symptoms to maximize the quality of life, and include the following:

• Corticosteroids such as prednisolone and deflazacort increase energy and strength and defer severity of some symptoms.
• Randomised control trials have shown that beta2-agonists increase muscle strength but do not modify disease progression. Follow-up time for most RCTs on beta2-agonists is only around 12 months and hence results cannot be extrapolated beyond that time frame.^{[citation needed]}
• Mild, non-jarring physical activity such as swimming is encouraged. Inactivity (such as bed rest) can worsen the muscle disease.
• Physical therapy is helpful to maintain muscle strength, flexibility, and function.
• Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care. Form-fitting removable leg braces that hold the ankle in place during sleep can defer the onset of contractures.
• Appropriate respiratory support as the disease progresses is important

Comprehensive multi-disciplinary care standards/guidelines for DMD have been developed by the Centers for Disease Control and Prevention (CDC), and were published in two parts in The Lancet Neurology in 2010. To download the two articles in PDF format, go to the TREAT-NMD website: http://www.treat-nmd.eu/patients/DMD/dmd-care/

Support Groups

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

Expectations (prognosis)

Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age 25, typically from lung disorders.

Complications

• Cardiomyopathy
• Congestive heart failure (rare)
• Deformities
• Heart arrhythmias (rare)
• Mental impairment (varies, usually minimal)
• Permanent, progressive disability
  
  • Decreased mobility
  • Decreased ability to care for self
• Pneumonia or other respiratory infections
• Respiratory failure

Calling your health care provider

Call your health care provider if:

• Your child has symptoms of Duchenne muscular dystrophy
• Symptoms worsen, or new symptoms develop, particularly fever with cough or breathing difficulties

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.

References

1. Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Muscular dystrophies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa:Saunders Elsevier; 2007:chap 608.