Molecular pathogenesis of Marfan syndrome

Int J Cardiol. 2015;187:585-91. doi: 10.1016/j.ijcard.2015.03.423. Epub 2015 Mar 31.


Marfan syndrome (MFS) is a genetic disorder that affects multiple organs. Mortality imposed by aortic aneurysm and dissections represent the most serious clinical manifestation of MFS. Progressive pathological aortic root enlargement as the result of degeneration of microfibril architecture and consequential loss of extracellular matrix integrity due to fibrillin-1 (FBN1) mutations are commonly diagnosed clinical manifestations of MFS. However, overlapping clinical manifestations with other aneurysmal disorders present a significant challenge in early and accurate diagnosis of MFS. While FBN1 mutations, abnormal transforming growth factor-β signaling and dysregulated matrix metalloproteinases have been implicated in MFS, clinically accepted risk-stratifying biomarkers have yet to be reliably identified. In this review, we summarize current consensus and recent insights in the understanding of MFS pathogenesis. Finally, we introduce the application of induced pluripotent stem cells (iPSCs) as cellular models for MFS and its potential as a novel platform into providing better appreciation of mechanisms underlying MFS diverse manifestations in the cardiovascular system.

Keywords: Aortic aneurysms; Fibrillin-1; Induced pluripotent stem cells; Marfan syndrome; TGF-β.

Publication types

  • Review

MeSH terms

  • Fibrillin-1
  • Fibrillins
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Marfan Syndrome / etiology*
  • Marfan Syndrome / genetics
  • Matrix Metalloproteinases / metabolism
  • Microfilament Proteins / genetics
  • Transforming Growth Factor beta / metabolism


  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins
  • Transforming Growth Factor beta
  • Matrix Metalloproteinases