Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery

Hum Mutat. 2016 Jun;37(6):524-31. doi: 10.1002/humu.22977. Epub 2016 Mar 14.


Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years.

Keywords: FBN1; LDS; Loeys-Dietz syndrome; MFS; Marfan syndrome; SKI; SMAD2; SMAD3; TGF-β signaling; TGFB2; TGFB3; TGFBR1; TGFBR2; thoracic aortic aneurysm.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Animals
  • Arachnodactyly / drug therapy
  • Arachnodactyly / genetics*
  • Craniosynostoses / drug therapy
  • Craniosynostoses / genetics*
  • Gene Expression Regulation
  • Gene Regulatory Networks / drug effects
  • Genetic Predisposition to Disease
  • Humans
  • Loeys-Dietz Syndrome / drug therapy
  • Loeys-Dietz Syndrome / genetics*
  • Marfan Syndrome / drug therapy
  • Marfan Syndrome / genetics*
  • Mitral Valve Prolapse / drug therapy
  • Mitral Valve Prolapse / genetics*
  • Myopia / drug therapy
  • Myopia / genetics*
  • Signal Transduction / drug effects
  • Skin Diseases / drug therapy
  • Skin Diseases / genetics*
  • Transforming Growth Factor beta / genetics*


  • Angiotensin Receptor Antagonists
  • Transforming Growth Factor beta

Supplementary concepts

  • MASS syndrome
  • Shprintzen Golberg craniosynostosis