MUSCULAR DYSTROPHY DEFINITION
Muscular dystrophy is a group of diseases that cause progressive weakness and loss of muscle mass. In muscular dystrophy, abnormal genes (mutations) interfere with the production of proteins needed to form healthy muscle.
There are many different kinds of muscular dystrophy. Symptoms of the most common variety begin in childhood, primarily in boys. Other types don’t surface until adulthood.
Some people who have muscular dystrophy will eventually lose the ability to walk. Some may have trouble breathing or swallowing.
There is no cure for muscular dystrophy. But medications and therapy can help manage symptoms and slow the course of the disease.
MUSCULAR DYSTROPHY CAUSES
Researchers are quickly learning more about what causes the genetic disorder that leads to muscular dystrophy, and about possible treatments for the disease.
There are many types of muscular dystrophy that are caused by mutations in several different genes. For example, Duchenne muscular dystrophy and Becker muscular dystrophy are caused by mutations in the dystrophin gene, whereas limb-girdle muscular dystrophies are caused by mutations in other genes.
MUSCULAR DYSTROPHY PATHOPHYSIOLOGY
Multiple proteins are involved in the complex interactions of the muscle membrane and extracellular environment. For sarcolemmal stability, dystrophin and the dystrophin-associated glycoproteins (DAGs) are important elements.
The dystrophin gene is located on the short arm of chromosome X near the p21 locus and codes for the large protein Dp427, which contains 3685 amino acids. Dystrophin accounts for only approximately 0.002% of the proteins in striated muscle, but it has obvious importance in the maintenance of the muscle’s membrane integrity.
Dystrophin aggregates as a homotetramer at the costomeres in skeletal muscles, as well as associates with actin at its N-terminus and the DAG complex at the C-terminus, forming a stable complex that interacts with laminin in the extracellular matrix. Lack of dystrophin leads to cellular instability at these links, with progressive leakage of intracellular components; this result in the high levels of creatine phosphokinase (CPK) noted on routine blood workup of patients with Duchenne MD.
Less-active forms of dystrophin may still function as a sarcolemmal anchor, but they may not be as effective a gateway regulator because they allow some leakage of intracellular substance. This is the classic Becker dystrophy. In both Duchenne and Becker MD, the muscle-cell unit gradually dies, and macrophages invade. Although the damage in MD is not reported to be immunologically mediated, class I human leukocyte antigens (HLAs) are found on the membrane of dystrophic muscles; this feature makes these muscles more susceptible to T-cell mediated attacks.
Selective monoclonal antibody hybridization was used to identify cytotoxic T cells as the invading macrophages; complement-activated membrane attack complexes have been identified in dystrophic muscles as well. Over time, the dead muscle shell is replaced by a fibrofatty infiltrate, which clinically appears as pseudohypertrophy of the muscle. The lack of functioning muscle units causes weakness and, eventually, contractures.
Other types of MDs are caused by alterations in the coding of one of the DAG complex proteins. The gene loci coding for each of the DAG complex proteins is located outside the X chromosomes. Gene defects in these protein products also lead to alterations in cellular permeability; however, because of the slightly different mechanism of action and because of the locations of these gene products within the body, there are other associated effects, such as those in ocular and limb-girdle type dystrophies
MUSCULAR DYSTROPHY SYMPTOMS
The main sign of muscular dystrophy is progressive muscle weakness. Specific signs and symptoms begin at different ages and in different muscle groups, depending on the type of muscular dystrophy.
Duchenne muscular dystrophy
About half of people with muscular dystrophy have this variety. Although girls can be carriers and mildly affected, the disease typically affects boys.
About one-third of boys with Duchenne muscular dystrophy don’t have a family history of the disease, possibly because the gene involved may be subject to sudden abnormal change (spontaneous mutation).
Signs and symptoms typically appear between the ages of 2 and 3, and may include:
- Frequent falls
- Difficulty getting up from a lying or sitting position
- Trouble running and jumping
- Waddling gait
- Walking on the toes
- Large calf muscles
- Muscle pain and stiffness
- Learning disabilities
Becker muscular dystrophy
Signs and symptoms are similar to those of Duchenne muscular dystrophy, but typically are milder and progress more slowly. Symptoms generally begin in the teens but may not occur until the mid-20s or even later.
Other types of muscular dystrophy
Some types of muscular dystrophy are defined by a specific feature or by where in the body symptoms first begin. Examples include:
- Myotonic. Also known as Steinert’s disease, this form is characterized by an inability to relax muscles at will following contractions. Myotonic muscular dystrophy is the most common form of adult-onset muscular dystrophy. Facial and neck muscles are usually the first to be affected.
- Facioscapulohumeral (FSHD). Muscle weakness typically begins in the face and shoulders. The shoulder blades might stick out like wings when a person with FSHD raises his or her arms. Onset usually occurs in the teenage years but may begin in childhood or as late as age 40.
- Congenital. This type affects boys and girls and is apparent at birth or before age 2. Some forms progress slowly and cause only mild disability, while others progress rapidly and cause severe impairment.
- Limb-girdle. Hip and shoulder muscles are usually the first affected. People with this type of muscular dystrophy may have difficulty lifting the front part of the foot and so may trip frequently. Onset usually begins in childhood or the teenage years.
MUSCULAR DYSTROPHY DIAGNOSIS
If a pediatrician suspects that a child may have muscular dystrophy, they will likely begin by testing the creatine kinase (CK) level in the blood. This muscle enzyme is very high in children with muscular dystrophy.
After finding a high CK level, the pediatrician will likely do DNA testing to look for mutations in the gene that makes dystrophin, an important muscle protein. If this genetic testing is negative, then a muscle biopsy may be done to confirm the diagnosis of muscular dystrophy.
Although it is possible to screen newborns for muscular dystrophy by testing their level of creatine kinase, it is not routinely done. One of the big problems is that only about 10 percent of newborns with a high CK level will actually have muscular dystrophy. The other 90 percent will have CK levels that return to normal when they are a few weeks old.
Often, there is a loss of muscle mass, which may be hard to see because some types of muscular dystrophy cause a buildup of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.
MUSCULAR DYSTROPHY TREATMENT
There’s no cure for any form of muscular dystrophy. But treatment can help prevent or reduce problems in the joints and spine to allow people with muscular dystrophy to remain mobile as long as possible. Treatment options include medications, physical therapy, and surgical and other procedures.
Your doctor may recommend:
- Corticosteroids, such as prednisone, which can help improve muscle strength and delay the progression of certain types of muscular dystrophy. But prolonged use of these types of drugs can cause weight gain and weaken bones, increasing fracture risk.
- Heart medications, such as angiotensin-converting enzyme (ACE) inhibitors or beta blockers, if muscular dystrophy damages the heart.
Several types of therapy and assistive devices can improve quality and sometimes length of life in people who have muscular dystrophy. Examples include:
- Range-of-motion and stretching exercises. Muscular dystrophy can restrict the flexibility and mobility of joints. Limbs often draw inward and become fixed in that position. Range-of-motion exercises can help to keep joints as flexible as possible.
- Exercise. Low-impact aerobic exercise, such as walking and swimming, can help maintain strength, mobility and general health. Some types of strengthening exercises also might be helpful. But it’s important to talk to your doctor first because some types of exercise might be harmful.
- Braces. Braces can help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Braces can also aid mobility by providing support for weakened muscles.
- Mobility aids. Canes, walkers and wheelchairs can help maintain mobility and independence.
- Breathing assistance. As respiratory muscles weaken, a sleep apnea device may help improve oxygen delivery during the night. Some people with severe muscular dystrophy may need to use a machine that forces air in and out of their lungs (ventilator).
Surgery may be needed to correct a spinal curvature that could eventually make breathing more difficult.