An update on the pathophysiology, treatment and genetics of Marfan syndrome

Abstract

Introduction: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue with manifestations in skeletal, cardiovascular and ocular systems. Areas covered: This paper reviews the effect of FBN1 mutation on phenotype, novel surgical techniques and losartan treatment in MFS. Expert opinion: Early diagnosis by the revised Ghent criteria and timely prophylactic (valve-sparing) aortic root replacement are important factors to improve life expectancy. Endovascular aortic stenting should not be done in MFS patients. β-blockers remain the drug of choice in preventing aortic dilation and dissection. Although controversial results are reported, losartan is a safe additive or alternative to β-blockers, especially in patients with side effects or intolerance to β-blocker therapy. The different outcomes in losartan trials may be due to the large amount of different FBN1 mutations, influencing the drug response; patients with an haploinsufficiency mutation seemed to respond better to losartan treatment than patients with a dominant negative mutation. In addition, patients with a haploinsufficiency mutation are at increased risk for aortic dissection and cardiovascular mortality. The final ongoing trials and collaborative meta-analysis are awaited for the definitive role of losartan in patients with MFS. Tremendous progress in the understanding of MFS has been reached.