Introduction to Duchenne Muscular Dystrophy.
"Muscular Dystrophy" is a broad term used to label gene-related disorders that affect muscles throughout the body. There are more than 20 specific genetic disorders considered to be Muscular Dystrophy. Most have the same result (a reduction in muscle strength due to weakening and deterioration) but these various types of Muscular Dystrophies are specific to different muscles in the body and different rates of degeneration.
All forms of Muscular Dystrophy are considered rare, but Duchenne Muscular , which is 100% fatal, affects approximately 1 in every 2,400 boys. Another type of Muscular Dystrophy, first diagnosed in the 1950s, is Becker Muscular Dystrophy (BMD). BMD occurs in about 1 in 18,000 male births and is considered to be a less severe form of Duchenne MD.
What does “dystrophy” mean?
The word “dystrophy” was coined in the 1860s by a French physician named Guillaume Duchenne when he noticed that the muscles in some young boys were weakening and wasting away. He called it a “dystrophy,” after the Greek word roots, "dys-" meaning abnormal, diseased or faulty and "-trophy" which refers to nutrition or growth. Duchenne believed that dystrophy progressed as muscles continued to develop without the nutrients they needed. Muscular dystrophy is always a genetic disorder, which means that it always results from a gene defect. This mutation may be inherited from a parent who also has it, even if it is not “expressed” (manifested). Such an inherited genetic flaw is called a “familial mutation.” All mutations begin somewhere, and it is possible that the mutation occurred long ago, in a previous generation. It is also possible that the mutation occurs only in the afflicted individual (or in the egg or sperm that created that person), in which case the new mutation is considered “spontaneous.” Duchenne MD is notable for the large proportion of cases (roughly 40%) that occur spontaneously.
The high incidence of spontaneous mutation in Duchenne MD is due to the large size of the dystrophin gene. The larger the gene, the greater the odds are that some error will occur. The term "muscular dystrophy" is considered by many to be misleading when it comes to DMD and BMD because technically, the muscles in boys with DMD do not lack any required nutrients. The problem actually stems from the absence of a critical muscle protein, called dystrophin. So DMD and BMD are best referred to as “myopathies” (from the Greek root "myo-" for muscle and "-pathos" for abnormal or diseased).
Myopathies occur when the fault lies in the muscle itself rather than in some other tissue that controls, serves or attaches to the muscle. But due to the common use and familiarity of the term “muscular dystrophy”, Duchenne Muscular Dystrophy is referred to as a muscular dystrophy.
What causes DMD?
Within our gene makeup, the dystrophin gene, one of the largest genes found to date, “codes” for an important muscle protein also called dystrophin. Dystrophin acts as the glue that holds muscles together by maintaining the structure of muscle cells. Dystrophin is also believed to carry signals between the inside and outside of muscle fibers. Without dystrophin, muscles are not able to operate properly and eventually suffer progressive damage.The dystrophin gene is carried on the X-chromosome. Boys are therefore more susceptible to dystrophin damage because they have only one X-chromosome. When a boy is diagnosed with Duchenne MD, his body is not able to produce any dystrophin. In Becker MD, a distorted, over-sized version of dystrophin is generated. In either disorder, without fully functional dystrophin, muscle cells within the body gradually weaken and eventually die.
What is dystrophin and what does it do?
Each gene, such as the dystrophin gene, “codes” for (carries the message to make) a specific and unique protein. These proteins help build the body, and help it to run smoothly. There are thought to be roughly 100,000 genes, and as many proteins, in each human. When a gene mutates, it produces a different protein than what it’s supposed to. Depending on which gene is altered and the severity of the mutation, it may not be a serious problem. But in the case of DMD, it is lethal. If the gene that codes for dystrophin is never turned on, or if a faulty type of dystrophin is produced, the fatal DMD results.
Dystrophin’s main function is to serve as a "connector" in the cell’s structural support system (or cytoskeleton). Dystrophin anchors contractile muscle filaments to the membrane (surrounding surface) of a muscle cell. Each protein has a unique three-dimensional structure. Different portions of this structure enable the protein to fold over onto itself or to connect with other molecules. This allows the entire cell to shorten during muscle contraction, generating the forces needed to move the skeleton. When any of these connecting membrane proteins is faulty, two things happen. First, muscle cannot contract normally, which leads to weakness since less force can be generated. Second, as a muscle cell contracts, its delicate membrane tears, spilling the contents of the cell into the surrounding fluid. Not only do vital substances leak out of muscle fibers, but harmful substances (like calcium ions) pour in. As with any injury to the body, normal immune cells (or lymphocytes) arrive to mend or remove the damaged cells and debris. The injured muscle cells are "cleared away" and are replaced with hard, fibrous or rubbery scar tissue. This leads to “pseudohypertrophy,” in which muscles (particularly of the calf) appear much larger than normal. Ironically, what appears to be a sign of strength is really a sign of weakness, as the increased mass consists not of strong muscle, but rather of useless scar tissue. This pseudohypertrophy is one of the early indicators that physicians use to diagnose Duchenne MD in young boys.
Yes. There are three types of muscle tissue. By far, the most common and familiar is the “skeletal” muscle that attaches to the bones. Skeletal muscle is what people typically think of when they hear the word "muscle." It is the prime target of Duchenne MD. Dystrophin is also found in the other two kinds of muscle: “cardiac” (of the heart) and “smooth” (of the digestive tract). Unlike skeletal, these muscles are involuntary, meaning that they cannot be moved at will. But like skeletal, dystrophin is integral in them as well.
How is DMD detected?
Duchenne MD is typically diagnosed in boys between the ages of 3 and 7. Usually parents will notice that their son is behind other boys their age in developmental milestones. Often, parents will notice that their son’s calves appear to be enlarged (pseudohypertrophy), which is another indicator that may result in a DMD diagnosis. Boys between the ages of 3 and 5 (pre-school) may appear to be clumsy and will often lose their balance, causing them to fall down a lot during regular activity. Climbing stairs, running and rising up from the floor becomes very difficult. By school age, Duchenne MD causes contractures (loss of elasticity) in their Achilles tendons, which forces them to walk either on their toes or on the balls of their feet, resulting in a "walk" that appears to be a waddle. In order to keep their balance and maintain their center of gravity, boys with Duchenne MD will stick out their bellies and push their shoulders back. This condition is called Lordosis. Between the ages of 7 and 12, most boys with Duchenne MD will lose their ability to walk and depend on a wheelchair for mobility. Throughout the years that follow, all activities that call for the use of arms, legs or trunk muscles will require assistance. Fatigue is a problem for boys with Duchenne MD. They struggle with normal levels of activity, but especially when much walking or stair climbing is required. If parents notice that their son grows excessively tired from these everyday tasks, they should consult a doctor. The doctor (or often physical therapist) will have the boy perform certain functional tests to assess the contractile ability of various muscles and the flexibility of joints, indicating a possible Duchenne MD diagnosis. These tests include walking, running, climbing, pulling, and rising from a sitting position.
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