Marfan syndrome. Part 1: pathophysiology and diagnosis

Nat Rev Cardiol. 2010 May;7(5):256-65. doi: 10.1038/nrcardio.2010.30. Epub 2010 Mar 30.


Marfan syndrome is a connective-tissue disease inherited in an autosomal dominant manner and caused mainly by mutations in the gene FBN1. This gene encodes fibrillin-1, a glycoprotein that is the main constituent of the microfibrils of the extracellular matrix. Most mutations are unique and affect a single amino acid of the protein. Reduced or abnormal fibrillin-1 leads to tissue weakness, increased transforming growth factor beta signaling, loss of cell-matrix interactions, and, finally, to the different phenotypic manifestations of Marfan syndrome. Since the description of FBN1 as the gene affected in patients with this disorder, great advances have been made in the understanding of its pathogenesis. The development of several mouse models has also been crucial to our increased understanding of this disease, which is likely to change the treatment and the prognosis of patients in the coming years. Among the many different clinical manifestations of Marfan syndrome, cardiovascular involvement deserves special consideration, owing to its impact on prognosis. However, the diagnosis of patients with Marfan syndrome should be made according to Ghent criteria and requires a comprehensive clinical assessment of multiple organ systems. Genetic testing can be useful in the diagnosis of selected cases.

Publication types

  • Review

MeSH terms

  • Animals
  • Aortic Aneurysm, Thoracic / diagnostic imaging
  • Aortic Aneurysm, Thoracic / genetics*
  • Aortic Aneurysm, Thoracic / physiopathology
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / physiopathology
  • Contractile Proteins / genetics*
  • Contractile Proteins / metabolism
  • Disease Models, Animal
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fibrillin-1
  • Fibrillins
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Humans
  • Male
  • Marfan Syndrome / diagnosis
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / physiopathology
  • Mice
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Prognosis
  • RNA Splicing Factors
  • Radiography
  • Risk Assessment
  • Survival Rate


  • Contractile Proteins
  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fbn1 protein, mouse
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins
  • RNA Splicing Factors
  • microfibrillar protein