What is Duchenne muscular dystrophy?

Risk Factors

Male children and children with a family history of DMD are at risk for the disease. Parents should tell their child’s doctor if their child has any of these risk factors.

Etiology and Genetics

All individuals with Duchenne muscular dystrophy have a mutation in the DMD gene, which is located on the short arm of the X chromosome at position Xp21.2. This is one of the largest human genes known, spanning more than two million base pairs of deoxyribonucleic acid (DNA). Its protein product is called dystrophin, a large molecule found primarily in skeletal muscles and cardiac muscles, but small amounts of the protein are also present in nerve cells in the brain. In muscle cells, dystrophin is the major protein in a complex of proteins that serves to anchor the internal cytoskeleton to the cell membrane and ultimately to the extracellular matrix. It also appears to participate in aspects of cell signaling, since it interacts with other proteins that are known to transmit chemical signals within and between cells. In muscles that lack dystrophin altogether or have a nonfunctioning version, the cell membrane becomes permeable, allowing extracellular matrix elements to enter the cell. The damage to the membrane increases with repeated muscle contractions and relaxations until eventually the cell dies. The resulting immune response can exacerbate the damage.

The inheritance pattern of Duchenne muscular dystrophy is typical of all sex-linked recessive mutations (those found on the X chromosome). Mothers who carry the mutated gene on one of their two X chromosomes face a 50-percent chance of transmitting this disease to each of their male children. Female children have a 50-percent chance of inheriting the gene and becoming carriers like their mothers. Females usually do not exhibit this disorder, since in order to be affected they would have to inherit the defective gene from both parents. Affected males almost never live to reproduce.

Symptoms

Parents whose child has any of these symptoms should not assume it is due to DMD. These symptoms may be caused by other conditions. Parents should tell their child’s doctor if their child has any of the symptoms.

Children who are late in learning to walk, have larger than normal calf muscles, frequently fall, walk clumsily, have difficulty climbing stairs, have trouble running, walk on their toes or the balls of their feet, have trouble with balance, walk with their shoulders back and belly out, and do not run may have DMD. Additional symptoms include trouble keeping up with friends when playing and using their hands to climb up their bodies when getting up from floor (Gower’s maneuver). Additional symptoms can occur later in the disease, including muscle contractures (a shortening of the muscle that traps a joint in a contracted position), scoliosis, weakness in respiratory muscles, cardiomyopathy (weakness of heart muscle), and learning disabilities.

Screening and Diagnosis

The doctor will ask about a child’s symptoms and medical history. A physical exam will be done. The doctor will also ask if there is any family history of neuromuscular disease. The exam will focus on the child’s muscles. The doctor will look for signs of weakness. Parents will likely be referred to a specialist.

Tests may include a muscle biopsy, a test that removes a small piece of muscle for examination and is used to detect abnormalities in the muscle; a creatine kinase (CK) level test, a blood test used to measure CK, an enzyme found in damaged muscle; genetic testing, a blood test that identifies the genetic mutation of DMD; and electromyography (EMG), a test that measures how well the nerves and muscles work and is used to detect muscle problems.

Treatment and Therapy

Parents should talk with their child’s doctor about the best plan for their child. The disease worsens over time; a child may need different treatments as the disease progresses.

Options include physical therapy, which plays a large role in treating DMD. A child will work with a therapist to try to keep muscles strong. The disease causes contractures; this is when a muscle shortens, making it difficult to move. The therapist will focus on preventing this with range of motion exercises. Scoliosis is common in DMD. Exercises can help to keep the back as straight as possible.

Braces are used to keep the legs straight and prevent contractures. A walker and wheelchair may be needed later, when the leg muscles become too weak to walk.

The doctor may prescribe a steroid medication like prednisone. This can help to improve muscle strength and slow muscle weakening. Steroids can weaken bones; to keep bones healthy, a child will take vitamin D and calcium supplements. A child who experiences heart problems may be given certain medications to slow the damage.

As the disease progresses, the muscles that support breathing may weaken. A child may need a ventilator, which will deliver air through a mask, tube, or sometimes through a tracheotomy (a surgical hole in the windpipe).

Surgery is sometimes used to treat symptoms of DMD. For severe contractures, surgery may be performed to release specific tendons. Scoliosis can sometimes interfere with a child’s breathing. In this case, back surgery may be done.

Prevention and Outcomes

There are no known guidelines to prevent this progressive muscle disease.

Bibliography

Brown, Robert H., Jr., Anthony A. Amato, and Jerry R. Mendell. “Muscular Dystrophies and Other Muscle Diseases.” Harrison’s Principles of Internal Medicine. Ed. Anthony S. Fauci et al. 18th ed. New York: McGraw-Hill Medical, 2012. Print.

Chamberlain, Jeffrey S., and Thomas A. Rando, eds. Duchenne Muscular Dystrophy: Advances in Therapeutics. New York: Taylor, 2006. Print.

"Duchenne Muscular Dystrophy." MedlinePlus. US Natl. Lib. of Medicine, 1 Feb. 2012. Web. 21 July 2014.

Emery, Alan E. H. Muscular Dystrophy: The Facts. 3rd ed. New York: Oxford UP, 2008. Print.

Emery, Alan E. H., and Francesco Muntoni. Duchenne Muscular Dystrophy. 3rd ed. New York: Oxford UP, 2003. Print.

Kellicker, Patricia Griffin. "Duchenne Muscular Dystrophy." Health Library. EBSCO Information Services, 23 May 2014. Web. 21 July 2014.