Pathophysiology and Pathogenesis of Marfan Syndrome

Adv Exp Med Biol. 2021:1348:185-206. doi: 10.1007/978-3-030-80614-9_8.


Marfan syndrome (MFS) is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern with variable penetrance. While clinically this disease manifests in many different ways, the most life-threatening manifestations are related to cardiovascular complications including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection. In the past 30 years, research efforts have not only identified the genetic locus responsible but have begun to elucidate the molecular pathogenesis underlying this disorder, allowing for the development of seemingly rational therapeutic strategies for treating affected individuals. In spite of these advancements, the cardiovascular complications still remain as the most life-threatening clinical manifestations. The present chapter will focus on the pathophysiology and clinical treatment of Marfan syndrome, providing an updated overview of the recent advancements in molecular genetics research and clinical trials, with an emphasis on how this information can focus future efforts toward finding betters ways to detect, diagnose, and treat this devastating condition.

Keywords: Aneurysm; Angiotensin receptor blockers (ARBs); Aorta; Collagen; Endoglin; Extracellular matrix; Extracellular signal related kinase (ERK); Fbn1C1039G/+; Fibrillin; Genetic testing; Ghent nosology; Loeys-Dietz syndrome (LDS); Losartan; Marfan syndrome (MFS); Metalloproteinase; Mitogen-activated protein kinase (MAPK); Mitral valve; SMAD; TGF-β receptor; Thoracic aortic aneurysm and dissection syndrome; Transforming growth factor-β (TGF-β); mgR/mgR; β-Blockers.

Publication types

  • Review

MeSH terms

  • Aorta
  • Aortic Dissection*
  • Fibrillin-1
  • Humans
  • Marfan Syndrome* / diagnosis
  • Marfan Syndrome* / genetics
  • Marfan Syndrome* / therapy
  • Transforming Growth Factor beta


  • Fibrillin-1
  • Transforming Growth Factor beta