Duchenne muscular dystrophy, or DMD, is the most common type of muscular dystrophy. The disease is characterized by progressive muscle weakness and wasting, and it more commonly affects males than females.
Causes of DMD
Duchenne muscular dystrophy is caused by mutations in the DMD gene, which provides cells with instructions for making a protein called dystrophin. Working in a complex with other proteins, dystrophin acts like a “shock absorber” in muscle cells, helping to protect the cells from wear-and-tear during the rigorous processes of muscle movements.
Thousands of different disease-causing mutations have been identified in the DMD gene. Most mutations that cause Duchenne result in a complete lack of functional dystrophin protein being produced. Mutations that result in a lower amounts of a working dystrophin protein tend to cause another form of muscular dystrophy, Becker muscular dystrophy (BMD), which usually has milder symptoms and later onset than DMD. Both DMD and BMD are dystrophinopathies, a broader term for disorders caused by dysfunctional dystrophin protein.
Inheritance of DMD
In most cases, mutations in DMD are passed from parents to their biological children. About one-third of DMD cases arise from de novo germline mutations — that is, non-inherited or newly occurring mutations that affect sperm or egg cells prior to conception.
The DMD gene is located on the X chromosome, which is one of the two sex-determining chromosomes in people: usually, females have two X chromosomes, while males have one X chromosome and one Y chromosome. DMD is much more common in males than in females because females get two X chromosomes and therefore copies of the DMD gene — so if one copy is mutated, the other copy is usually able to compensate. DMD affects about one in 3,500 male births, while less than one in one million girls are born with the disease.
Females with one mutated copy of the DMD gene are often referred to as “carriers,” because they will not develop the disease themselves but they can pass the disease-causing mutation to their biological children. While most carriers show no symptoms of DMD, some may experience milder symptoms associated with muscular dystrophy.
Symptoms of DMD
DMD’s main symptom is muscle wasting that progressively worsens over time. The disease usually first affects the proximal muscles, or muscles that are closer to the trunk of the body — muscles around the hips and upper legs are often the first affected, with other parts of the body impacted as the disease progresses.
Usually, children with DMD first show signs of the disease around age 2 or 3. The earliest symptoms often include trouble standing and climbing stairs, a waddling (duck-like) gait, and frequent falls.
Children often miss normal developmental milestones; for example, being unable to walk by 15 months, or having difficulty talking compared to similarly aged peers. The calves may be enlarged due to the buildup of scar and fat tissue in damaged muscles. About one in three people with DMD exhibit cognitive impairment or learning disabilities.
As the disease progresses, muscle weakness makes walking difficult. Most people with DMD rely on a wheelchair to get around by the time they are teenagers. As muscle wasting continues, patients often develop scoliosis (a sideways curvature of the spine) and contractures — when muscles become shortened, restricting movement of the joints. Weakness in muscles that move food through the digestive tract can cause constipation and other digestive problems.
DMD also can cause damage to muscles of the heart, as well as the muscles in the chest needed for breathing. Patients may often require a ventilator to help them breathe by the time they reach adulthood.
Management and prognosis of DMD
Although DMD currently has no cure, advances in medical care have made it possible for patients to live longer and more fulfilling lives. A major component of caring for people with DMD is providing regular monitoring, and giving support where needed, to help slow or stop problems from developing.
Current guidelines strongly recommend that people with DMD be regularly treated with anti-inflammatory medications called corticosteroids from the time they start experiencing symptoms. There are also several approved exon-skipping therapies, which promote the production of a working dystrophin protein, for people with specific disease-causing mutations.
Non-pharmaceutical interventions also can be beneficial for many people with DMD — for example, physical therapy can help maintain motor function, speech therapy may aid patients with difficulty speaking, and occupational therapy can help patients in navigating day-to-day life while managing their disease. Ventilators can help patients with breathing difficulties, and surgeries can be helpful for managing severe scoliosis.
With optimal care, most people with DMD now live to be 20 to 40 years old; the most common causes of death are heart failure and respiratory failure. While living with DMD can certainly affect a person’s quality of life, patients often report life quality that is similar or only moderately lower than their peers without the disease.
Notably, studies have shown that people with DMD usually rate their own life quality more positively than their caregivers do.
Last updated: Jan. 19, 2022, by Marisa Wexler MS
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