Definitions

becker muscular dystrophy

Becker's muscular dystrophy

Becker's muscular dystrophy (also known as Benign pseudohypertrophic muscular dystrophy) is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis.

It is a type of dystrophinopathy, which includes a spectrum of muscle diseases in which there is insufficient dystrophin produced in the muscle cells, resulting in instability in the structure of muscle cell membrane. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker's muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but in Duchenne muscular dystrophy no functional dystrophin is produced making DMD much more severe than BMD. Both Duchenne and Becker's muscular dystrophy have traditionally been called "X-linked" recessive diseases, but in view of modern molecular biology and identification of the dystrophin gene, it might be more appropriate to say they are X-chromosome recessive diseases.

Eponym

Becker's is named after the German doctor Peter Emil Becker.

Genetics

The disorder is inherited with an X-linked recessive inheritance pattern. The gene is located on the X chromosome. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate. In these cases, some women have much milder symptoms because of this ability to compensate. For example, carrier females of mutations are at increased risk for dilated cardiomyopathy. Since men have an X and a Y chromosome and because they don't have another X to compensate for the defective gene, they will develop symptoms if they inherit the non-working gene.

All dystrophinopathes are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother. Carrier females have a 50% chance of passing the DMD mutation in each pregnancy. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker's muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their father's mutation. Prenatal testing through amniocentesis or chorionic villus sampling (CVS) for pregnancies at risk is possible if the DMD mutation is found in a family member or if informative linked markers have been identified.

Becker's muscular dystrophy occurs in approximately 3 to 6 in 100,000 male births. Symptoms usually appear in men at about ages 8-25, but may sometimes begin later. Patients can lose the ability to walk as early as age 15. Women rarely develop symptoms.

Genetic counseling is indicated for individuals or families who may carry this condition.

Symptoms

  1. Muscle weakness, slowly progressive (Difficulty running, hopping, jumping; Progressive difficulty walking)
  2. Ability to walk may continue into adulthood (up to age 40). Patients don't generally live past age 60.
  3. Frequent falls
  4. Difficulty breathing
  5. Non progressive cognitive dysfunction only in rare cases: not as common as in duchenne because the brain only needs small amounts of dystrophin
  6. Skeletal deformities, chest and back (scoliosis)
  7. Muscle deformities (contractions of heels, legs; Pseudohypertrophy of calf muscles)
  8. Fatigue
  9. Heart disease

People with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the arms, neck, and other areas, but not as noticeably severe as in the lower half of the body.

Calf muscles initially enlarge during the ages of 5-15 (an attempt by the body to compensate for loss of muscle strength), but the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy) as the legs become less used (use of wheelchair).

Muscle contractions occur in the legs and heels, causing inability to use the muscles because of shortening of muscle fibers and fibrosis of connective tissue. Bones may develop abnormally, causing skeletal deformities of the chest and other areas.

Cardiomyopathy (damage to the heart) does not occur as commonly with this disorder as it does with Duchenne's muscular dystrophy. Cognitive problems may accompany the disorder, but they are not inevitable and do not worsen as the disorder progresses.

Signs and tests

The pattern of symptom development resembles that of Duchenne's muscular dystrophy, but with a later, and much slower rate of progression. Noticeable signs of Muscular Dystrophy also include the lack of pectroral and upper arm muscles, especially when the disease is unnoticed through the early teen years. Muscle wasting begins in the legs and pelvis (or core), then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy may occur, but the development of congestive heart failure or arrhythmias (irregular heartbeats) is rare.

Treatment

There is no known cure for Becker's muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life.

Activity is encouraged. Inactivity (such as bed rest) can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength. Orthopedic appliances such as braces and wheelchairs may improve mobility and self-care.

Genetic counseling may be advisable. Sons of a man with Becker's muscular dystrophy do not develop the disorder, but daughters will be carriers. The daughters' sons may develop the disorder.

Immunosuppressant steroids like Prednisone have been known to help slow the progression of Becker Muscular Dystrophy. The drug contributes to an increased production of the protein Utrophin which closely resembles Dystrophin, the protein that is defective in BMD.

A hepatitis C drug "Debio-025" that has proven safe for use in Europe shows much promise for halting the muscle necrosis seen in the disease. The investigational drug Debio-025 is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researches decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the disease’s muscle-damaging characteristics. The mice were engineered as models of Duchenne muscular dystrophy and forms caused by a deficiency of two structural proteins, delta-sarcoglycan and laminin alpha2.

“Similar to deleting the gene encoding cyclophilin D, we found that treatment with Debio-025 reduced mitochondrial swelling and necrotic manifestations in mice with muscular dystrophy. This is why we believe inhibiting cyclophilin D could be a new treatment strategy,” said Jeff Molkentin, Ph.D., corresponding author of the study and a researcher in the Division of Molecular Cardiovascular Biology at Cincinnati Children’s. “Debio-025 has already passed Phase II clinical trials in Europe and is considered safe in people, so we want to explore the possibility of conducting clinical trials in patients with Duchenne MD.”

During the onset of muscular dystrophy, the loss of certain proteins critical to muscle function – such as dystrophin – can lead to contraction-related micro-tears in muscle fibers and an influx of calcium around muscle tissue. When this happens, cyclophilin D is instructed to make the membranes of mitochondria more permeable. This causes mitochondria to be flooded by calcium and reorganize, swell and eventually rupture. This triggers cell death in muscle fibers and leads to the progressive muscle weakness, wasting and often early death associated with muscular dystrophy.

Expectations (prognosis)

Becker's muscular dystrophy results in slowly progressive disability. Death can occur in the 60s but some patients live to an advanced age.

Complications

Quality of Life

The quality of life for patients with Becker's muscular dystrophy need not be impacted by the symptoms of the disorder. With assistive devices, independence can be maintained indefinitely. People affected by Becker's muscular dystrophy can still drive, work, own businesses, and maintain active lifestyles. Those affected by the disorder can also still participate in sports for the disabled, such as wheelchair tennis, Power Soccer, and sled hockey

References

External links

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