|Duchenne muscular dystrophy|
Classification and external resources
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. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books 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 structural component of muscle tissue. Dystrophin is a rod-shaped Cytoplasmic Protein, and a vital part of a Protein complex that connects the Cytoskeleton of a Muscle fiber 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. Fibrosis is the formation or development of excess fibrous Connective tissue in an organ or tissue as a reparative or reactive process as opposed to a formation of Fibrous By age 10, braces may be required for walking, and most patients are confined to a wheelchair by age 12. Later symptoms include abnormal bone development that leads to skeletal deformities including curvature of the spine, which can be corrected by orthapedic surgery improving the quality of life and extending life. Progressive loss of movement may lead to eventual paralysis, and may increase difficulty in breathing. Intellectual impairment may also be present but does not progress as the child ages. The Life Expectancy of someone with DMD varies from the late teens to age 35, however there have been people with the disease who make it to age 40.
Duchenne muscular dystrophy occurs in approximately 1 out of 4,000 people and can either be inherited or occur spontaneously. A family history of Duchenne muscular dystrophy is a significant risk factor.
DMD is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806-1875), who first described the disease in the 1860s. Guillaume Benjamin Amand Duchenne (born September 17, 1806 in Boulogne; died September 15, 1875) was a French Neurologist 
Duchenne muscular dystrophy is caused by a mutation of the dystrophin gene at locus Xp21. In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Dystrophin is responsible for the connection of muscle fibers to the extracellular matrix through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (cell membrane). Dystrophin is a rod-shaped Cytoplasmic Protein, and a vital part of a Protein complex that connects the Cytoskeleton of a Muscle fiber Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 The sarcolemma is the Cell membrane of a muscle cell It consists of a true cell membrane called the plasma membrane and an outer coat made up of a thin layer of polysaccharide In a complex cascading process that involves several pathways and is not clearly understood, increased oxidative stress within the cell damages the sarcolemma, eventually results in the death of the cell. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily The sarcolemma is the Cell membrane of a muscle cell It consists of a true cell membrane called the plasma membrane and an outer coat made up of a thin layer of polysaccharide Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue. Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. "Adipose" redirects here For the Doctor Who monster see " Partners in Crime " Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial, Muscle, and Nervous tissue)
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 (or "lack of strength" is a direct term for the inability to exert force with one's Muscles to the degree that would be expected given the individual's Muscle atrophy is defined as a decrease in the mass of the muscle it can be a partial or complete wasting away of muscle 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:
Muscle wasting begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Scoliosis is a medical condition in which a person's spine is curved from side to side and may also be rotated Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy may occur, but the development of congestive heart failure or arrhythmias (irregular heartbeats) is rare. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply Dysrhythmia redirects here For the American band see Dysrhythmia (band.
If a physician suspects DMD after examining the boy they will use a CPK (creatine phosphokinase) test to determine if the muscles are damaged. Creatine kinase (CK also known as creatine phosphokinase (CPK or phosphocreatine kinase, is an Enzyme ( expressed by various tissue types This test measures the amount of CPK in the blood. In DMD patients CPK leaks out of the muscle cell into the bloodstream, so a high level (50 to 100 times normal) confirms that there is muscle damage. Affected individuals may have a value as high as 15,000 to 35,000iu/l (normal = 60iu/l).
The muscle-specific isoform of the dystrophin gene is composed of 79 exons, and DNA testing and analysis can usually identify the specific type of mutation of the exon or exons that are affected. An exon is a Nucleic acid sequence that is represented in the mature form of an RNA molecule after a portions of a precursor RNA Introns have been DNA testing confirms the diagnosis in most cases. 
If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted and a dye is applied that reveals the presence of dystrophin. Complete absence of the protein indicates the condition.
Over the past several years DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of Duchenne's.
If one or both parents are 'carriers' of a particular condition there is a risk that their unborn child will be affected by that condition. 'Prenatal tests' are carried out during pregnancy, to try to find out if the fetus (unborn child) is affected. The tests are only available for some neuromuscular disorders. Different types of prenatal tests can be carried out after about 10 weeks of pregnancy. Chorion villus sampling (CVS) can be done at 10-12 weeks, and amniocentesis at about 14-16 weeks, while placental biopsy and foetal blood sampling can be done at about 18 weeks. Women and/or couples need to consider carefully which test to have and to discuss this with their genetic counselor. Earlier testing would allow early termination which would probably be less traumatic for the couple, but it carries a slightly higher risk of miscarriage than later testing (about 2%, as opposed to 0. 5%).
There is no known cure for Duchenne muscular dystrophy, although recent stem-cell research is showing promising vectors that may replace damaged muscle tissue. Treatment is generally aimed at control of symptoms to maximize the quality of life, and include the following.
Duchenne muscular dystrophy eventually affects all voluntary muscles and involves the heart and breathing muscles in later stages. The life expectancy can range from the late teens to the age of 35, However there have been people with duchennes who made it to age 40.  Recent advancements in medicine are extending the lives of those afflicted. Orthapedic Surgery for scoliosis also extend the life of someone with the illness. All People W/ the DMD illness is affected differently.
Physical therapists are concerned with enabling children to reach their maximum physical potential. Their aim is to:
Modern "volume ventilators/respirators," which deliver an adjustable volume (amount) of air to the person with each breath, are valuable in the treatment of people with muscular dystrophy related respiratory problems. Ventilator treatment can begin in the mid to late teens when the respiratory muscles can begin to collapse. However there are people with the disease in there 20's who have no need for a ventillator.
If the vital capacity has dropped below 40 percent of normal, a volume ventilator/respirator may be used during sleeping hours, a time when the person is most likely to be under ventilating ("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). In Medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate ( hypo means "below" to perform needed A sleep disorder (somnipathy is a medical disorder of the Sleep patterns of a person or animal Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement The ventilator may require an endotracheal or tracheotomy tube through which air is directly delivered, however, for some people delivery through a face mask is sufficient. Tracheotomy and tracheostomy are Surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe
If the vital capacity continues to decline to less than 30 percent of normal, a volume ventilator/respirator may also be needed during the day for more assistance. The person gradually will increase the amount of time using the ventilator/respirator during the day as needed. A tracheotomy tube may be used in the daytime and during sleep, however, delivery through a face mask may be sufficient. The machine can easily fit on a ventilator tray on the bottom or back of a power wheelchair with an external battery for portability.
Promising research is being conducted around the globe to find a cure or a therapy that is able to mitigate some of the effects of the disease. Finding a cure is made more complex by the number and variation of genetic mutations in the dystrophin gene that result in DMD.
In the area of stem cell research, a recent paper was published in Nature Cell Biology that describes the identification of pericyte-derived cells from human skeletal muscle. These cells, mesoangioblasts, have been shown to fulfill important criteria for consideration of therapeutic uses. That is, they are easily accessible in postnatal tissue, they are able to grow to a large enough number in vitro to provide enough cells for systemic treatment of a patient, they have been shown to differentiate into skeletal muscle, and, very important, they can reach skeletal muscle through a systemic route. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism This means that they can be injected arterially and cross through arterial walls into muscle, unlike therapeutic cell types used earlier such as muscle satellite cells which require the impractical task of intramuscular injection. These findings show potential for stem cell therapy of DMD. In this case a small biopsy of skeletal muscle from the patient would be collected, the pericyte-derived cells would be extracted and grown in culture, and then these cells would be injected into the blood stream where they could navigate into and differentiate into skeletal muscle.
The research group of Kay Davies works on the upregulation of utrophin, a smaller but similar protein that is found in fetal humans, as a substitute for dystrophin. Dame Kay Elizabeth Davies, DBE, FRS, is a British human Geneticist born on April 1 1951 Utrophin, also known as UTRN, is a human Gene. The protein encoded by this gene is a component of the Cytoskeleton. Dystrophin is a rod-shaped Cytoplasmic Protein, and a vital part of a Protein complex that connects the Cytoskeleton of a Muscle fiber
At the Généthon Institute in Evry near Paris under Olivier Danos and Luis García the U7 gene transfer technique is under development. 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. An exon is a Nucleic acid sequence that is represented in the mature form of an RNA molecule after a portions of a precursor RNA Introns have been Sense, when applied in a Molecular biology context is a general concept used to compare the polarity of Nucleic acid molecules such as DNA or RNA An oligonucleotide (or oligo) is a short segment of RNA or DNA, typically with twenty or fewer bases. 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 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).
Antisense techniques can also modify splicing of pre-mRNA, similarly converting Duchenne to Becker-like muscular dystrophy in animal models but without the need for insertion of DNA by virus. Because these techniques do not permanently modify the DNA, they are more accurately considered as potential treatments rather than cures. Especially promising for this application are Morpholino antisense oligos. In Molecular biology, a Morpholino is a Molecule used to modify Gene expression.  Morpholinos are commencing Phase 1 clinical trials in the EU. An experiment in Leiden with an oligonucleotide has shown partial restoration(3-12% of normal) of dystrofin synthesis in locally injected muscle in human patients. Although this is an important finding it is not a practical form of treatment .
More information on the new PTC124 trials, currently nearing the end of Phase II, is available at the MDA. PTC124 is a novel small-molecular agent that makes Ribosomes less sensitive to Stop codons However it is not equally effective with every stop codon working best org website. This potential treatment would address from 5 to 15 percent of DMD cases where the dystrophin protein cannot be completed due to an incorrect stop codon in the genetic sequence. In the Genetic code, a stop codon (or termination codon) is a Nucleotide triplet within Messenger RNA that signals a termination of translation The PTC124 treatment skips the improper "stop" instruction, allowing reading through of the remaining sequence and completion of the dystrophin protein assembly process. In recent mouse trials, PTC124 was found to repair damaged muscle tissues. 
Recent research shows losartan, a currently available drug used for treating hypertension, to be effective in halting the progress of the disease in mice that were genetically engineered to have Duchenne's. Losartan ( rINN) (loʊˈsɑrtən is an Angiotensin II receptor antagonist drug used mainly to treat high blood pressure ( Hypertension)  Human trials are in planning.
Some parents of children with Duchenne's are noting reductions of symptomatic severity from a regimen of Protandim, a non-prescription nutritional supplement that increases levels of two specific antioxidant enzymes. Other parents report no benefit. Controlled clinical trials have not yet been conducted, and parent observations may have been influenced by confounding factors such as expectation bias, normal developmental progress, and the common practice of implementing additional nutritional supplements and/or corticosteroids concurrent with the Protandim. However, Protandim is promising on a theoretical level, in that it has the potential to modify the inflammatory/cell death cycle. DMD mouse-model trials of the therapy are in progress, and human trials are planned. 
Research from a group in France led by L. Ségalat has identified a number of drugs that are currently licenced for other applications as halting or reducing dramatically the advance of muscle degeneration in a worm model of DMD.  They are now using mouse models to confirm these findings, which so far are looking very promising, confirming the efficacy of these drugs. However, work in mice seems to be moving slowly. The main classes of drugs they identified were SSRI (ie antidepressants such as prozac) and muscle relaxants, such as those used by athletes after heavy training. There is conflicting evidence from animal models suggeseting that doing less exercise slows down the rate of degeneration of the muscle; therefore there is a possibility that both these drugs act somewhat as sedatives, although the reality seems to be that the worms and mice are more active overall, as they have less muscle damage and so can remain active for much longer.
More recently, a group at the Montreal Heart Institute and McGill University reported that a mouse model of Duchenne's muscular dystrophy demonstrated early metabolic alterations that precede overt cardiomyopathy and may represent an early "subclinical" signature of a defective nitric oxide (NO)/cGMP pathway. Cardiomyopathy, which literally means "heart muscle disease" is the deterioration of the function of the Myocardium (i Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] Accordingly, they used genetic and pharmacological approaches to test the hypothesis that enhancing cGMP, downstream of NO formation, improves the contractile function, energy metabolism, and sarcolemmal integrity. Treatment with sildenafil delayed the appearance of symptoms in mouse hearts with Duchenne's and allowed to withstand an acutely increased cardiac workload. Sildenafil citrate, sold as Viagra, Revatio and under various other trade names is a drug used to treat Erectile dysfunction (male impotence 
Genetic counseling is advised for people with a family history of the disorder. Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.
In addition to charities devoted to muscular dystrophies in general (such as MDA), these charities are devoted exclusively to DMD: