The disease is caused by a mutation in the DMD gene , which encodes for a protein called dystrophin. Dystrophin acts to protect the muscles at each contraction, and a lack of dystrophin results in an accumulation of damage and eventual death of the muscle cells.
Genes are organized in chromosomes , long pieces of tightly packaged DNA. We all have 23 pairs of chromosomes. Pairs 1 to 22 have the same genes on them. Females inherit two copies of the X chromosome one from their mother and one from their father , while males inherit one X chromosome from their mother and one Y chromosome from their father.
The DMD gene is located on the X chromosome, so Duchenne muscular dystrophy is an X-linked disease and mostly affects males because they have only one copy of the X-chromosome. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence.
The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate. Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy.
This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat arrhythmia , shortness of breath, extreme tiredness fatigue , and swelling of the legs and feet.
These heart problems worsen rapidly and become life-threatening in most cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond. A related condition called X-linked dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy.
People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. Duchenne and Becker muscular dystrophies together affect 1 in 3, to 5, newborn males worldwide. Between and boys in the United States are born with these conditions each year.
The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells. Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use.
The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Although DMD often runs in a family, it is possible for a family with no history of DMD to suddenly have a son with the disease. There are two possible explanations. The first is that the genetic mutation leading to DMD may have existed in the females of a family for some generations without anyone knowing.
Perhaps no male children were born with the disease, or, even if a boy in an earlier generation was affected, relatives may not have known what disease he had. A man with DMD cannot pass the flawed gene to his sons because he gives a son a Y chromosome, not an X. They will then be carriers, and each of their sons will have a 50 percent chance of developing the disease and so on.
A good way to find out more about the inheritance pattern in your family is to talk to your MDA Care Center physician or a genetic counselor. When a girl inherits a flawed dystrophin gene from one parent, she usually also gets a healthy dystrophin gene from her other parent, giving her enough of the protein to protect her from the disease.
Males who inherit the mutation get the disease because they have no second dystrophin gene to make up for the faulty one. Early in the embryonic development of a female, either the X chromosome from the mother maternal X or the one from the father paternal X is inactivated in each cell. Chromosomes become inactivated at random. In each cell, there is a 50 percent chance that either the maternal or paternal X chromosome will be inactivated, with the other left active.
Usually, girls do not experience the full effects of DMD the way boys do, although they still have symptoms of muscle weakness. A minority of females with the mutation, called manifesting carriers , have some signs and symptoms of DMD. For these women, the dystrophin deficiency may result in weaker muscles in the back, legs, and arms that fatigue easily.
Manifesting carriers may have heart problems, which can show up as shortness of breath or an inability to do moderate exercise.
The heart problems, if untreated, can be quite serious, even life-threatening. In very rare instances, a girl may lack a second X chromosome entirely, or her second X may have sustained serious damage. In these cases, she makes little or no dystrophin depending on the type of dystrophin mutation , and she develops a dystrophinopathy just as a boy would.
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