| Duchenne Muscular Dystrophy |
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Information AboutDuchenne Muscular Dystrophy |
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| muscular dystrophy | |
| genetic disorders | |
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DMD is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806-1875), who first described the disease in the 1860s. One third of the cases are known to be caused by development of Spontaneous Mutation s in the dystrophin gene, while the remainder are inherited. Boys with DMD develop weak muscles because the muscle fibers that were present at birth are destroyed. It is due to mutations in the Dystrophin gene, which encodes a cell membrane protein in myocytes (muscle cells). GENETICS Duchenne dystrophy is a type of dystrophinopathy which includes a spectrum of muscle disease caused by mutations in the DMD Gene , which encodes the protein dystrophin. Becker's Muscular Dystrophy is a milder type of dystrophinopathy. Although it is caused by a defective gene, it often occurs in people from families without a known family history of the condition. Duchenne muscular dystrophy is inherited in an X-linked Recessive pattern. Because of random X Inactivation , some women carriers can actually be partially affected by this disease, despite its recessive nature. X inactivation leads to women being in a state of X0, not XX as is usually thought (see below). Women who carry the defective gene can pass an abnormal X on to their sons. Since boys have an X from their mother and a Y from father, there is no second X to make up for the defective gene from the carrier mother. The sons of carrier females each have a 50% chance of having the disease, and the daughters each have a 50% chance of being carriers. Daughters of men with Duchenne will always be carriers, since they will inherit an affected X chromosome from their father (note that the diagram only shows the results from an unnaffected father).Some females will also have very mild degrees of MD, and it is known as a manifesting carrier. Prenatal Testing , such as Amniocentesis , for pregnancies at risk is possible if the DMD disease-causing mutation has been identified in a family member or if informative linked markers have been identified. In 30% of the cases, the disease is a result of a spontaneous mutation. In some female cases, DMD is caused by skewed x inactivation. In these cases, two copies of the x chromosome exist, but for reasons currently unknown, the flawed x chromosome manifests instead of the unflawed copy. In these cases, a mosaic form of DMD is seen, in which some muscle cells are completely normal while others exhibit classic DMD findings. The effects of a mosaic form of DMD on long-term outlook is not known. SYMPTOMS
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 enlarge -- the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy). Muscle contractures occur in the legs, rendering the muscles unusable because the muscle fibers shorten and Fibrosis occurs in Connective Tissue . TREATMENT There is no known cure for Duchenne muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life. Physical activity is encouraged. Inactivity (such as bed rest) can worsen the muscle disease. Physical and occupational therapy may be helpful to maintain muscle strength and function. Orthopaedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care. Support Groups Joining a support group where members share common experiences and problems can often help relieve the stress of this illness. See muscular dystrophy - support group. The Muscular Dystrophy Association (www.mda.org) is an excellent source of information on this disease. Also, the Parent Project (parentprojectmd.org) is another excellent source of support and information. Expectations (prognosis) Duchenne muscular dystrophy results in rapidly progressive disability. Death usually occurs by age 25, typically from respiratory (lung) disorders. Physiotherapy Physiotherapists are concerned with enabling children to reach their maximum physical potential. Their aim is to:
Mechanical Ventilatory Assistance: Volume Ventilators Modern "volume ventilators," which deliver a preset volume (amount) of air to the child with each breath, are valuable in the treatment of children with muscular dystrophy related respiratory problems. When the vital capacity has dropped below 40 percent of normal, a volume ventilator may be used during sleeping hours, a time when the child is most likely to be underventilating ("hypoventilating"). Hypoventilation during sleep is determined by a thorough history of sleep disorder with an oximetry study and a capillary blood gas (See Pulmonary Function Testing). The ventilator requires a nasal or facemask for connection to the airway. The masks are constructed of comfortable plastic with Velcro straps to hold them in place during sleep. As the vital capacity declines to less than 30 percent of normal, a volume ventilator may also be needed during the day for more assistance. The child gradually will increase the amount of time using the ventilator during the day as needed. A mouthpiece can be used in the daytime and a nasal or facemask can be used during sleep. The machine can easily fit on a ventilator tray on the bottom of a power wheelchair. There may be times such as during a respiratory infection when a child needs to rest his/her respiratory muscles during the day even when not yet using full-time ventilation. The versatility of the volume ventilator can meet this need, allowing tired breathing muscles to rest and also allowing aerosol medications to be delivered. RESEARCHING A CURE Promising research is being conducted around the globe to find a cure, or at the least a therapy that is able to mitigate some of the devastating effects of the disease. For example, at the Généthon Institute in Evry near Paris by the team of Olivier Danos and Luis García. This new technique is a combination of Exon Skipping and the transfer of a gene that instructs the muscle cells to continuously produce the Antisense-oligonucleotides (AONs) themselves so that they do not have to be injected repeatedly. The AONs are potential drugs which are able to modify the genetic information in such a way that the fast progressing Duchenne muscular dystrophy is converted into the much slower developing Becker muscular dystrophy. Early research into the effects of this treatment (known as U7 Gene Transfer) have been very promising. Treated mice have gone on to show very little muscle weakness even after being stressed. Treated monkeys have retained the active AONs 6 years after injection, and treated dogs have developed 80% of the normal muscle mass within 2 months of treatment. First round tests in humans are due to begin soon, but given the need for multiple rounds of testing before a treatment can be released to the public, it will be at least a few years before this cure is widely available (if indeed these results are possible in humans). For a comprehensive report on the studies prepared by Dr. Guenter Scheuerbrandt, you may download the PDF file . Although this report is intended to be undertsandable by the families of those affected, it is written in a highly technical manner and many readers may find it incomprehenisble. PREVENTION Genetic counseling is advised if there is a family history of the disorder. Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy. EXTERNAL LINKS |