Marfan syndrome: from molecular pathogenesis to clinical treatment

摘要

Marfan syndrome is a connective tissue disorder with ocular, musculoskeletal and cardiovascular manifestations that are caused by mutations in fibrillin-1, the major constituent of extracellular microfibrils. Mouse models of Marfan syndrome have revealed that fibrillin-1 mutations perturb local TGFβ signaling, in addition to impairing tissue integrity. This discovery has led to the identification of a new syndrome with overlapping Marfan syndrome-like manifestations that is caused by mutations in TGFβ receptor types I and II. It has also prompted the idea that TGFβ antagonism will be a productive treatment strategy in Marfan syndrome and perhaps in other related disorders. More generally, these studies have established that Marfan syndrome is part of a group of developmental disorders with broad and complex effects on morphogenesis, homeostasis and organ function.