Muscular dystrophy

Muscular dystrophy is one of the most frequently encountered genetic diseases, affecting an estimated 1 in every 3500 males (but many fewer females). It is associated with the progressive degeneration of skeletal and cardiac muscle fibers, weakening the muscles and leading ultimately to death from respiratory or cardian failure.

Muscular dystrophies are caused are caused by the absence or defect of one or more proteins that make up the costameres in striated muscles. Costameres are clusteres of structural and regulatory proteins that link the Z disks of the outermost myofibrils to the sarcolemma and extracellular matrix. Proteins of the costameres serve multiple roles, including lateral transmission of force from the sarcomeres to the extracellular matrix and neighboring muscle fibers, stabilization of the sarcolemma against physical forces during muscle fiber contraction or stretch, and initiation of intracellular signals that link contractile activity with regulation of muscle cell remodeling. Defects in a number of specific costamere proteins have been demonstrated to cause various types of muscular dystrophy.

Duchenne muscular dystrophy is a sex-linked recessive disorder caused by a defect in a gene on the X chromosome that codes for the protein dystrophin. It is more common in males since they possess only 1 X chromosome, which increases the possibility of the expression of the defected gene. The defected gene can result in either a nonfunctional or missing protein leading to muscle fibers susceptibility to membrane rupture and death. The condition therefore progresses with muscle use and age. Symptoms of weakness in the muscles of the hip girdle and trunk become evident at about 2 to 6 years of age and most affected individuals do not survive far beyond the age of 20. Preliminary attempts are being made to treat the disease by inserting the normal gene into dystrophic muscle cells.

The other major forms of Muscular Dystrophy are Becker, limb-girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss muscular dystrophy.

References:

• National Institutes of Health: Department of  Health and Human Services. Report to Congress on Implementation of the Muscular Dystrophy Community Assistance. c2006 [cited 2006 May]. URL: http://www.ninds.nih.gov/find_people/groups/mdcc/md_care_implementation.pdf.
• Widmaier EP, Raff H, Strang KT. Vander's Human Physiology: the mechanisms of body function. 12 ed. New York: McGraw-Hill International Edition; 2011.