Pediatric Cardiology and Cardiac Surgery
Vol.25 No.4 2009 (594-599)
Hiroko Morisaki and Takayuki Morisaki
Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan
Abstract
Marfan syndrome (MFS; MIM154700) is an autosomal dominant hereditary disorder of the fibrous connective tissue with cardinal manifestations in the skeletal, ocular, and cardiovascular systems, caused by the defects in the FBN1 gene. The clinical diagnosis of MFS is made using the Ghent criteria. Although the criteria are useful in classical MFS, cases with recently reported Loeys-Dietz syndrome, caused by mutations in the TGFBR1 or TGFBR2 genes, often manifest many overlapping features of MFS and sometimes fulfill the Ghent criteria. Recent advances in the molecular pathogenesis of MFS also have revealed that many manifestations of MFS are less related to a primary structural deficiency of the tissues than to altered morphogenetic and homeostatic programs that are induced by altered TGF-β signaling. In 2006, losartan, a widely used angiotensin II type-1-receptor antagonist, was shown to prevent aortic aneurysm in a mouse model of MFS through its known effect in antagonizing TGF-β activity. This review provides an overview of recent advances in the molecular pathogenesis of MFS and a therapeutic view of this disorder.