Marfan Syndrome
Marfan’s Syndrome
Marfan syndrome is an inherited connective-tissue disorder transmitted as an autosomal dominant trait. It is distributed worldwide, has a high prevalence rate and has pleiotropic manifestations, meaning one gene influences multiple traits that do not seem to be related.
Mutations of the FBN1 gene on the 15th chromosome (more specifically chromosome 15q21.1) cause Marfan syndrome. The FBN1 gene is coded to make a glycoprotein called fibrillin-1. “This protein is an essential component of microfibrils that are major structural and regulatory components in the extracellular matrix” (Keane & Pyeritz, 2009, p. 3). Fibrillin-1 binds to other fibrillin-1 proteins and also to other molecules to form threadlike filaments called microfibrils. These microfibrils constitute the structural components of the suspensory ligament of the lens and serve as bases for elastin in the aorta and other connective tissues Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. These are not just critical to structural formation, but they also store molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. Production of abnormal fibrillin-1 monomers from the mutated gene disrupts the formation of multiple polymers of fibrillin-1 and prevents microfibril formation. This pathogenetic mechanism has been termed dominant-negative because the mutated fibrillin-1 disrupts microfibril formation though the other fibrillin gene encodes normal fibrillin. This mutation in the FBN1 gene reduces the amount of functional fibrillin-1 that is available to form microfibrils. As a result, excess growth factors are released (transforming growth factor-beta receptors 1 and 2) and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues.
Risk Factors Mafan syndrome occurs among
Marfan syndrome is an inherited connective-tissue disorder transmitted as an autosomal dominant trait. It is distributed worldwide, has a high prevalence rate and has pleiotropic manifestations, meaning one gene influences multiple traits that do not seem to be related.
Mutations of the FBN1 gene on the 15th chromosome (more specifically chromosome 15q21.1) cause Marfan syndrome. The FBN1 gene is coded to make a glycoprotein called fibrillin-1. “This protein is an essential component of microfibrils that are major structural and regulatory components in the extracellular matrix” (Keane & Pyeritz, 2009, p. 3). Fibrillin-1 binds to other fibrillin-1 proteins and also to other molecules to form threadlike filaments called microfibrils. These microfibrils constitute the structural components of the suspensory ligament of the lens and serve as bases for elastin in the aorta and other connective tissues Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. These are not just critical to structural formation, but they also store molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. Production of abnormal fibrillin-1 monomers from the mutated gene disrupts the formation of multiple polymers of fibrillin-1 and prevents microfibril formation. This pathogenetic mechanism has been termed dominant-negative because the mutated fibrillin-1 disrupts microfibril formation though the other fibrillin gene encodes normal fibrillin. This mutation in the FBN1 gene reduces the amount of functional fibrillin-1 that is available to form microfibrils. As a result, excess growth factors are released (transforming growth factor-beta receptors 1 and 2) and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues.
Risk Factors Mafan syndrome occurs among