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Monday, June 23, 2014

What is Marfan syndrome ?

Marfan syndrome (also called Marfan's syndrome) is a genetic disorder caused by the misfolding of the protein fibrillin-1. Fibrillin-1 is coded by the gene FBN1.[1][2] People with Marfan tend to be unusually tall, with long limbs and long, thin fingers. It is named afterAntoine Marfan,[3] the French pediatrician who first described the condition in 1896.[4][5] The gene linked to the disease was first identified by Hal Dietz[6][7] and Francesco Ramirez in 1991.[8]
Marfan syndrome is an autosomal dominant disorder, meaning that people who inherit only one copy of the Marfan FBN1 gene from either parent will develop Marfan syndrome and be able to transmit it to their children. Marfan syndrome has various expressions ranging from mild to severe: the most serious complications are defects of the heart valves and aorta. Additionally, it may affect thelungs, eyes, dural sac surrounding the spinal cord, the skeleton, and the hard palate.
Marfan syndrome is known as a connective tissue disorder. Fibrillin-1 protein forms fibers in connective tissue. In addition to providing structural support, the normal fibrillin-1 protein also contributes to cell signaling activity, binding to the protein transforming growth factor beta (TGF-β). Mis-regulated TGF-β has deleterious effects on vascular smooth muscle development and the integrity of the extracellular matrix.
Researchers now believe, secondary to mutated structural fibrillin, excessive TGF-β at the lungs, heart valves, and aorta weakens the tissues and causes the features of Marfan syndrome. Since angiotensin II receptor antagonists (ARBs) also reduce TGF-β, ARBs (such as losartan) have been tested in a small sample of young, severely affected people with Marfan syndrome. In some, the growth of the aorta was reduced

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