2011 Group Project 10

--Mark Hill 12:44, 5 August 2011 (EST) This belongs on your discussion page.

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Your Project Goes Here.

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2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

Introduction: What is Duchenne Muscular Dystrophy? (DMD)

-Severe -childhood onset -difficulty walking/mobility, breathing -range of other problems it can cause

Aetiology - Genetics

The largest gene of the human genome is called the dystrophin gene. This codes for the dystrophin protein which plays a very important role in the structural stability of muscle fibres. In DMD, there is a mutation in this gene that causes an absence or severe reduction in the production of the dystrophin protein.

Pathogenesis

Dystrophin is needed in all muscle cells of the body - this includes skeletal muscles, smooth muscles (like in organs and blood vessels) and cardiac muscle. Without dystrophin, the muscle cells can be easily damaged - the cell membrane becomes very permeable and allows extracellular material in. This causes the cell to swell until the pressure causes it to burst. Muscle fibres can also split, or begin a detrimental cycle of repeated necrosis and regeneration. Any dead muscle material is removed by macrophages, and then replaced by fatty or connective tissue. As a result, the muscle cells become extremely weak and atrophies.

Clinical manifestations (signs and symptoms)

Skeletal muscle: The degeneration of skeletal muscle causes many problems with mobility. In early childhood, a child affected with DMD may take longer than other children to sit or begin standing and walking. Young children may develop a waddling gait, a characteristic feature of DMD . As the disease progresses, walking (especially up stairs), and many children are confined to a wheelchair by the time they are 10. In addition to difficulties with walking, muscles of the arms and hands may also be affected.

Smooth muscle:

Cardiac muscle:

Diagnosis

• Clinical Diagnosis - in males: progressive symmetrical muscle weakness, symptoms present before age 5, elevated kinase blood levels.

• Muscle biopsy - a sample of muscle can be taken to look for abnormal levels of dystrophin in the muscle. A special stain is used to detect the dystrophin protein. In a unaffected patient, dystrophin will appear as though there is caulking around the individual muscles cells and it is holding them together like window panes. A patient suffering from DMD will have an absence of the dystrophin.

• Genetic Testing - this is achieved through a blood sample analysis. Changes in the DMD gene can be detected through various methods. E.g. Large changes in gene (deletion/duplication) or smaller components that spell out the instructions found within the DMD gene (sequencing). However, results may not be conclusive since changes in the genetic code by go undetected by the methods used.

A combination of these components along with family history confirms the diagnosis.

Treatment: Current and Future Prospects

Currently, there is no known cure for DMD. However, there a variety of treatments available which are aimed at managing the symptoms, protecting muscle mass and maximising the quality of life for those who suffer from DMD. Treatments includes:

• Physical Therapy: in order to maintain muscle strength and function. (Inactivity leads to weakened muscles and can worsen the condition)
• Orthopedic appliances such as braces and wheelchairs are available to improve mobility
• Aggressive management of dilated cardiomyopathy with anti-congestive medications
• The medication prednisone — a corticosteroid — is given to improve the strength and function of individuals with DMD (However there are side affects associated with this medication)

Future Therapies

• Poloxamer 188
• Idebenone
• Gene Therapy
• Stem Cell transplant
• Exon Skipping therapy

Glossary of terms

• Creatine kinase: an enzyme normally highly concentrated within muscle cells. As muscle cells degenerate, their contents are released into the bloodstream. Therefore elevated levels of creatine kinase can be detected by a blood test and is a measure of muscle damage.