Muscular dystrophy

The muscular dystrophies are a wide group of genetic and hereditary muscle diseases. Muscular dystrophies cover more than 20 specific genetic defects. Most of the dystrophies can be characterized by the same symptoms, but they usually differ in the course of disease. These diseases are characterized mainly by progressive skeletal muscle weakness, defects in muscle proteins and the death of muscle cells and tissue. In some forms of muscular dystrophy cardiac and smooth muscles are affected.

Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophies. This disorder is characterized by rapidly progressive muscle weakness, which starts in the legs and pelvis and later affects the whole body. DMD occurs in approximately 1 in 3500 male births. It was first described in 1860s by French neurologist G. B. A. Duchenne.

Duchenne muscular dystrophy is caused by mutations in the gene responsible for the production of the dystrophin protein (the second largest gene in mammals). DMD is an X-linked recessive inherited disease - the dystrophin gene is located on the X chromosome, therefore this disease is sex-linked (it can be found in males, because males have only one copy of the X chromosome, while females have two).

Women with defective gene can pass an abnormal X chromosome on to their sons. Since boys have an X chromosome from their mother and a Y chromosome from their father, there is no second X chromosone to make up for the defective gene from the carrier mother. The sons of carrier females have a 50% chance of having the disease, and the daughters have a 50% chance of being carriers. Daughters of men with Duchenne will always be carriers, because they will inherit an affected X chromosome from their father.

In 30% of cases, the disease is a result of a spontaneous mutation. In very rare cases daughters can be also affected and can develop symptoms (random X inactivation).

The main symptoms of Duchenne muscular dystrophy are rapidly progressive muscle weakness and muscle wasting with the proximal muscles being first affected (especially the pelvis and calf muscles). 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. First symptomsof the disease can appear at the age of 3. The other symptoms of DMD include:

• awkward gait
• frequent falls
• difficulty with motor skills (running, hopping, jumping)
• progressive difficulty walking
• ability to walk is usually lost by the age of 12
• fatigue
• skeletal deformities (including scoliosis in some cases)
• muscle deformities
• pseudohypertrophy of tongue and calf muscles
• musclar contractures of the heels and legs, rendering them unusable

Duchenne muscular dystrophy eventually affects all voluntary muscles, and the heart and breathing muscles. Symptoms result in death by age 30 and respiratory failure (most common cause of death in this case) usually results in a life expectancy of 20 years.

Becker muscular dystrophy

Becker muscular dystrophy (BMD) is a milder form of Duchenne muscular dystrophy. In this case most of the symptoms are similar to the DMD, but the onset is later and the course of the disease is milder. BMD can be characterized by slowly progressive muscle weakness of the legs and pelvis associated with a loss of muscle mass. Muscle weakness also occurs in the arms, neck, and other areas, but not to such an extent as in the lower half of the body.

Mechanisms causing Becker muscular dystrophy are similar to the mechanisms causing Duchenne muscular dystrophy. Both diseases result from a mutation in the dystrophin gene. The difference is that in the case of DMD no functional dystrophin is produced, while in the case of BMD a small amount of dystrophin of poor quality is produced. The Duchenne muscular dystrophy is therefore much more severe than the Becker's type.

Becker muscular dystrophy is named after German physician P. E. Becker, who first described this type of disease in 1950.

BMD occurs in approximately 1 in 170000 male births. Symptoms usually appear in males at the age of 12 or 13 (sometimes later). The average age of becoming unable to walk is 25-30.

Symptoms of Becker muscular dystrophy usually include:

• slowly progressive muscle weakness (difficulty running, hopping, jumping; progressive difficulty walking)
• ability to walk may continue into adulthood (up to age 40)
• frequent falls
• difficulty breathing
• cognitive dysfunction
• skeletal deformities
• muscle deformities
• fatigue
• heart disease

In the case of BMD death usually occurs in the fifth decade but some patients live to an advanced age.

Treatment

Currently there is no known cure for Duchenne/Becker muscular dystrophy. Treatment of patients is aimed at the control of symptoms to prolong life and maximize its quality. Physical activity is encouraged, because inactivity can often make muscle disease worse. Physical and occupational therapy can help to support muscles and their functionality.

Prevalence

DMD/BMD prevalence:

Numbers of female carriers are approximately the same.

References

• Department of Health and Human Services, Centers for Disease Control and Prevention [www.cdc.gov]
• Encyclopaedia Britannica [http://www.britannica.com]
• European Neuromuscular Centre [http://www.enmc.org]
• Parent Project Czech Republic [http://www.parentproject.cz]
• Wikipedia [http://wikipedia.org]