The Genetics of Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is the most common genetic disease fatal in children, it is a severe and rapidly progressive muscle disease with symptoms that first become evident due to the affected child showing early motor developmental delay; for example, presentation of Gower’s sign, a diagnostic indicator of proximal muscle weakness characterised by the affected having to “walk” their hands up their body to stand due to little strength being present in the lower limb.
By thirteen years of age the proximal muscle weakness is so advanced that the affected will be wheelchair dependent, and as involuntary muscles (cardiac and respiratory) grow more affected towards the age of eighteen, cardiomyopathy and respiratory diseases are common and often cause death, with very few survivors past the age of thirty and the average lifespan at twenty-five.
The cause of Duchenne Muscular Dystrophy is the occurrence of mutations in the Dystrophin (DMD) gene. The cytogenetic location off the DMD gene is Xp21.2; meaning at location 21.2 on the short arm of the X chromosome from base pair 31,119,219 to base pair 33,339,609. DMD is the biggest human gene currently known and instructs for the production of a 427 kDa protein by the same name. The dystrophin protein is part of the dystrophin associated protein complex which is expressed at the sarcolema and anchors muscle cellcytoskeletons to the extracellular matrix in skeletal and cardiac muscle,
Boys begin to have difficulty sitting up and standing, weakness that progresses to muscles in the trunk and shoulder, and later affecting the heart muscle. By the age of twenty years individuals affected with Duchenne dystrophy die.
Duchenne muscular dystrophy was first discovered by Guillaume Benjamin Amand Duchenne in the 1860’s, but due to lack of medical knowledge little was known until the 1980’s. It was in 1986 that researchers that were supported by the MDA, muscular dystrophy association, identified the particular X-chromosome that leads to DMD, Duchenne muscular dystrophy. Dystrophin is the protein that is associated with the gene and was named in 1987.The DMD gene is the second largest gene to date, and it produces dystrophin.(Genome, 2013) Lack of the protein Dystrophin in the muscle cells causes them to weaken and become fragile. (MDA, 2015). DMD is an inherited disorder, but there are rare cases where it can spontaneously appear in a child with no previous family history due to a random mutation in moms X-chromosome. DMD is a gender specific disease that only appears in males.
Credibility Statement: According to the "Muscular Dystrophies" by Harvey B.Sarnat in Nelson Textbook of Pediatrics, 20th Ed 2016, "A muscular dystrophy is distinguished from all other neuromuscular diseases by 4 obligatory criteria: It is a primary myopathy, it has a genetic basis,
Listener Relevance: Duchenne Muscular Dystrophy (DMD), is more common than people think and chances are sooner or later you will know of or see somebody affected by this disease.
Muscular dystrophy is an inherited disease that was discovered in 1861, by Guillaume B.A. Duchenne. Muscular dystrophy is a group of heredity disorders characterized by rapidly-worsening muscle weakness. The trait for muscular dystrophy may be transmitted as an autosomal dominant which means a disorder that has two copies of an abnormal gene that must be present in order for the disease or trait to develop. In this case, if some original carrier of the disease had children, the children would have a fifty-fifty chance of inheriting the disease. It is also carried as an autosomal recessive trait, in which case the offspring of the original carrier would have a very small chance of
Duchenne muscular Dystrophy (DMD) is the most common out of nine types of muscular dystrophy. This genetic disorder causes progressive muscular weakness, and deterioration due to the lack of a protein called Dystrophin. This protein keeps the muscles in tack, so when it's missing, the muscles slowly break down. (MDA, 2015)
Duchenne Muscular Dystrophy (also referred to as DMD) is a type of muscular dystrophy that weakens the muscles that we need to support our body, body weight, to stand, and to move around. It also can cause you to have scoliosis. Some of the main causes for DMD are genetic disorders, mutations, and DMD has to be passed down throughout everyone in that family for generations. The symptoms you can have if you have DMD are weak muscles, lack of strength, and difficulty walking. DMD is a negative mutation because it affects your muscles horribly bad that you can get a disability of walking and even moving. You need to tell your doctor immediately if you experience any symptoms. If you don't tell your doctor, you may find yourself in a very difficult situation where you can't get up or can't get something you need. When you do talk to your doctor, you will have an advantage of getting the help you need.
muscular dystrophy has many forms and therefore symptoms can vary between the variations. Overall symptoms include the weakening of skeletal muscles and the defect and death muscle tissues. Duchenne muscular dystrophy is the most common and affects young boys such as Eddie.
Duchenne Muscular Dystrophy is a sex-linked disease, which is inherited in a recessive fashion (National Human Genome Research Institute, 2013). Over thirty similar genetic disorders exist (Duchenne Foundation Australia, 2015). All types of muscular dystrophy are considered to be a rare disorder (Duchenne Foundation Australia, 2015). Duchenne Muscular Dystrophy is most common in children and causes muscle weakness and wasting, which commonly begins in the lower limbs (Duchenne Foundation Australia, 2015; National Human Genome Research Institute, 2013). The disease itself is caused by changes to the DMD gene, which is responsible for providing instructions regarding the creation of the dystrophin protein in one’s muscles (Duchenne Foundation Australia, 2015). This protein is responsible for protecting muscles from damage, and without it the cells of a person’s muscles deteriorate and symptoms of Duchenne Muscular Dystrophy are exhibited (Duchenne Foundation Australia, 2015). The disease results from changes in the DMD gene, or other genetic changes in a child (Duchenne Foundation Australia, 2015).
Duchenne muscular dystrophy, classified as a genetic disorder, is marked by progressive muscle degeneration and weakness. It is only one of the nine forms of muscular dystrophy; however, around half of the people diagnosed with muscular dystrophy have Duchenne muscular dystrophy.
Muscular Dystrophy is a genetic disease in which muscle fibers are usually susceptible to damage and cause muscle wasting and weakness. There are bundles of fibers that make up muscles; proteins are involved in these muscles and help to keep the muscle working properly. If
Duchenne Muscular Dystrophy (DMD) refers to the muscle appearing poorly nourished because of degeneration, which leads to muscle weakness and lost of muscle mass. DMD is a disorder that is caused by genetic mutations in the dystrophin gene. Dystrophin is a muscle that connects the cytoskeleton to the extracellular matrix (ECM). Tidy, D. C. (2016, April 15). When nonsense mutation or frameshift mutation occurs in dystrophin, it results in no protein at all, which causes a severe form of DMD. A dystrophin gene has more base pairs and more exons in comparison to most genes, which means the dysophin gene has a higher chance for mistakes during meiosis. The disorder affects one in 5000 newborn males. Tidy, D. C. (2016, April 15). Males have one
(Chad Haldeman-Englert, 2014) The symptoms usually appear before age 6 and may appear as early as infancy. One of the first noticeable symptom of this disease is the delay in motor milestones; many with Duchenne will take longer to independently stand, sit or walk than average child. (National Human Genome Research Institute, 2013) In toddlers, their enlarged calf muscles causing them to frequently fall over whilst moving. The child may experience occasional pain in the calves and may have some difficulty raising their arms. There is a steady decline in muscle strength between the ages of 6 and 11 years. Most boys are confined to a wheelchair by the age of 12. Muscular weakness and skeletal deformities often leads to respiratory issue. The diaphragm and other muscles that operates the lungs may start to weaken, making it hard to circulate fresh air into the body. The risk of serious respiratory infection is very high. Cardiomyopathy, a chronic disease of the heart muscle that is often a result of the DMD. Most boys will develop this heart disease in their early teens. One third of boys with DMD have some degree of learning disability. Majority of their learning problems occurs in focusing, verbal learning and memorising, and personal interaction. (The Muscular Dystrophy Association (MDA), 2016) Some of the symptoms, such as respiratory infection and cardiomyopathy are common causes of death in DMD
Currently, there are 9 major forms of muscular dystrophy which include: Myotonic, Becker, Limb-girdle, Facioscapulohumeral, Congenital, Oculopharyngeal, Distal, Emery-Dreifuss, and Duchenne muscular dystrophy (Mayo Clinic, 2014). For the purpose of this paper, the cause, as well as the impact of Duchenne muscular dystrophy on development, will be discussed.
Muscular dystrophy can be diagnosed with a physical exam and diagnostic testing completed by the child’s pediatrician. Additional information that will be obtained during the examination will be family history, pregnancy history, and birth history. Diagnostic studies for muscular dystrophy include muscle serum enzymes (especially creatine kinase), electromyogram (EMG) testing, muscle fiber biopsy, electrocardiogram abnormalities reflective of cardiomyopathy, and genetic pedigree (Lewis, 2011). Duchenne muscular dystrophy is caused by the lack of dystrophin. A muscle biopsy can be done to confirm a diagnosis of muscle dystrophy. The biopsy will show evidence of significant fat and connective tissue deposits, deterioration and necrosis of muscle fibers, and a lack of the muscle