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| DiseaseID |
HGD59 |
| Genetic
Disorder |
Duchenne muscular dystrophy
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| Gene
Name |
myogenic factor 6 (herculin) |
| Description |
Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy that is characterized by decreasing muscle mass and progressive loss of muscle function in male children. This disorder is caused by a mutation in a specific gene within the X chromosome that provides instructions for the formation of the dystrophin protein, an important component of muscle tissue. Females can be carriers but generally do not experience the symptoms of the condition. Symptoms usually appear in male children before age 6 and may occur as early as infancy. Progressive muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed and eventually spreads to the arms, neck, and other areas. Early signs may include enlarged calf muscles (pseudohypertrophy), low strength and endurance levels, and difficulties in standing up and walking on stairs. As the condition progresses, muscle tissue experiences wasting and fibrosis, and is eventually replaced by fat and connective tissue. By age 10, braces may be required for walking, and most patients are confined to a wheelchair by age 12. Later symptoms include contractures, abnormal bone development that leads to skeletal deformities including curvature of the spine, complete loss of movement, and increasing difficulty in breathing. Intellectual impairment may also be present but does not progress as the child ages. The condition is terminal and death usually occurs before the age of 30. Duchenne muscular dystrophy occurs in approximately 2 out of 10,000 people and can either be inherited or occur spontaneously. A family history of Duchenne muscular dystrophy is a significant risk factor.
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| Symptoms |
The main symptom of Duchenne muscular dystrophy is rapidly progressive muscle weakness associated with muscle wasting with the proximal muscles being first affected, especially the pelvis and calf muscles. Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body. Symptoms usually appear before age 6 and may appear as early as infancy. Generalized weakness and muscle wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged. The other physical symptoms are:
Awkward gait (patients tend to walk on their forefeet, because of an increased calve tonus)
Frequent falls
Difficulty with motor skills (running, hopping, jumping)
Progressive difficulty walking
Eventual loss of ability to walk (usually by the age of 12)
Fatigue
Higher risk of behaviour and learning difficulties.
Skeletal deformities (including scoliosis in some cases)
Muscle deformities.
Pseudohydrotrophy of tongue and calf muscles. The enlarged muscle tissue is eventually replaced by fat and connective tissue, hence the term pseudohypertrophy.
Mscle contractors of heels and legs, rendering them unusable because the muscle fibers shorten and fibrosis occurs in connective tissue.
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| Causes |
Duchenne muscular dystrophy is a rapidly-worsening form of muscular dystrophy . It is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition. This disorder is marked by worsening loss of muscle function, which begins in the lower limbs.
Duchenne muscular dystrophy is inherited in what is known as an X-linked recessive pattern. The defective gene is found on the X chromosome. Because women have two X chromosomes, if one contains a normal copy of the gene, that gene will make enough of the protein to prevent symptoms. But boys have an X chromosome from their mother and a Y from father, so if the X chromosome is defective, there is no second X to make up for it and they will develop the disease.
The sons of carrier females (women with one defective chromosome but no symptoms themselves) each have a 50% chance of having the disease, and the daughters each have a 50% chance of being carriers.
Symptoms usually appear before age 6 and may appear as early as infancy. There is progressive muscle weakness of the legs and pelvis, which is associated with a loss of muscle mass ( wasting ). Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body.
Calf muscles initially grow larger -- the enlarged muscle tissue is eventually replaced by fat and connective tissue (a condition called pseudohypertrophy). Muscle contractures occur in the legs. Thus, the muscles are unusable because the muscle fibers shorten and fibrosis (scarring) occurs in connective tissue.
By age 10, braces may be required for walking, and by age 12, most patients are confined to a wheelchair. Bones develop abnormally, causing skeletal deformities of the spine and other areas.
Muscular weakness and skeletal deformities contribute to frequent breathing disorders. Cardiomyopathy occurs in almost all cases. Intellectual impairment may occur, but it is not inevitable and does not worsen as the disorder progresses. |
| Diagnosis |
The diagnosis of MD is based upon a combination of a characteristic clinical presentation and the results of muscle biopsy.
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| Treatment |
There is no specific treatment to cure or halt MD. Physical therapy, exercise, orthopedic appliances (such as braces and wheelchairs), or corrective orthopedic surgery may help to preserve muscle function and prevent joint contractures as much as possible and improve quality of life. Steroids have been used to slow disease progression, but do not effect the final outcome. Identification of the specific genes responsible for the various types of MD has led to extensive research on gene and molecular therapy, but all such treatments are still experimental. Genetic counseling is recommended for families of affected individuals to ascertain the carrier status of other family members so that prenatal testing can be offered. |
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