The translational science of Marfan syndrome

Abstract

Marfan syndrome has changed over the last few years: new diagnostic criteria have been proposed, new clinical entities recognised and life expectancy increased. The role of fibrillin 1, which was initially thought to be mainly structural, has been shown to also be functional. The altered transforming growth factor β pathway is better understood, the importance of epigenetic factors has been demonstrated and recent data suggest that many of the observations made in Marfan syndrome can actually be made in thoracic aortic aneurysm from diverse aetiologies. Besides transforming growth factor β, the role of metalloproteinase, the fibrinolytic/coagulation system, is being suggested in the progression of the disease. A relationship between the type of fibrillin 1 (FBN1) gene mutation and the mechanism for the disease (haplo-insufficiency vs negative dominance), as well as some genotype/phenotype correlations, has been observed, although the main challenge of recognising gene modifiers has yet to explain tremendous variability despite similar mutation. This progress has led to new hopes for tomorrow's therapies, some of which are being tested in clinics, whereas others are still in the field of animal models. Here we review some of the new data obtained in the understanding of the pathophysiology and genetics of this disease.