|
Hey Folks
I've read the Wikipedia page for BMD many times and don't think it does a very good job of describing BMD. I've edited sections of it, but I think we need to give it a work over, since it's what most people find when they are searching about BMD. I'm going to copy the text below....just post a reply with the sections that you want to change and give us your changes....you don't have to rewrite the whole thing....just pick a small chunk that you think needs to be revised. At some point I'll compile all the feedback into a single revised text that we can submit to Wiki...
Make sure that this description covers your experience...I think together we can paint a better picture.
******************
Becker 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 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 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 Muscular Dystrophy is named after the German doctor Peter Emil Becker. [1][2][3]
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 dystrophinopathies 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 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. A significant number of Becker muscular dystrophy mutations are spontaneous and are not inherited from a parent.
Becker muscular dystrophy occurs in approximately 3 to 6 in 100,000 male births, making it much less common than Duchenne muscular dystrophy. 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 in the very rare severe form. Women rarely develop symptoms, but may do so due to mosaicism.
Genetic counseling is indicated for individuals or families who may carry this condition.
Symptoms
- Muscle weakness, slowly progressive (Difficulty running, hopping, jumping; Progressive difficulty walking)
- Toe-walking (walking on toes; also known as equinus)
- Use of Gower's Maneuver or a modified form of Gower's Maneuver to get up from floor.
- Ability to walk may continue well into adulthood. (Very variable.)
- Frequent falls
- Difficulty breathing
- Non progressive cognitive dysfunction only in rare cases: not as common as in Duchenne Muscular Dystrophy because the brain only needs small amounts of dystrophin.
- Skeletal deformities, chest and back (scoliosis)
- Muscle deformities (contractions of heels, legs; Pseudohypertrophy of calf muscles)
- Fatigue
- Heart disease
- Elevated CPK (creatine phosphokinase) levels in blood: Elevated CK levels are more common at younger ages and decreases later in life, perhaps due to the fact that muscle degeneration occurs more rapidly at younger ages, when there is also more muscle mass to deteriorate.
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, which may be painful, 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 or may not 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 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 (some men are not diagnosed with BMD until they are in their thirties). 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 muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life.
Activity is encouraged. Inactivity (such as bed rest) or sitting down for too long on plane or car rides 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 when potential carriers or patients want to have children. Sons of a man with Becker muscular dystrophy do not develop the disorder, but daughters will be carriers (and some carriers can experience some symptoms of muscular dystrophy). 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. IVIG has proved better in the long term, but its price is a limiting factor.
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.
The progression of Becker muscular dystrophy is highly variable-- much more so than Duchenne muscular dystrophy. There is also a form that may be considered as an intermediate between Duchenne and Becker MD (mild DMD or severe BMD). Severity of the disease may be indicated by age of patient at the onset of the disease. One study showed that there may be two distinct patterns of progression in Becker muscular dystrophy: one subgroup which experiences its onset at around age 7 to 8 years of age- this group typically has more cardiac involvement and has trouble climbing stairs by age 20; the other subgroup, which has its onset at around age 12, typically has significantly less cardiac involvement and can still easily climb stairs by age 20.[4] The mean age of onset is age 11, with variation from age 2 to 21. [5]
Becker's muscular dystrophy results in slowly progressive disability, and patients eventually use a cane or wheelchair. Death can occur from age 40 but some patients enjoy a nearly normal lifespan.
Complications
Quality of Life
The quality of life for patients with Becker muscular dystrophy need not be impacted by the symptoms of the disorder. With assistive devices, independence can be maintained. People affected by Becker muscular dystrophy can still drive, work, own businesses, start families, 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. |
