J Med Genet 43:769-787 doi:10.1136/jmg.2005.039669
  • Review

The molecular genetics of Marfan syndrome and related disorders

  1. P N Robinson1,
  2. E Arteaga-Solis2,
  3. C Baldock3,
  4. G Collod-Béroud4,
  5. P Booms5,
  6. A De Paepe6,
  7. H C Dietz7,
  8. G Guo1,
  9. P A Handford8,
  10. D P Judge9,
  11. C M Kielty3,
  12. B Loeys6,
  13. D M Milewicz10,
  14. A Ney1,
  15. F Ramirez11,
  16. D P Reinhardt12,
  17. K Tiedemann12,
  18. P Whiteman8,
  19. M Godfrey13
  1. 1Institute of Medical Genetics, Charité University Hospital, Humboldt University, Berlin, Germany
  2. 2Department of Pediatrics, Mount Sinai School of Medicine-New York University, One Gustave L. Levy Place, New York, NY 10029, USA
  3. 3Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK
  4. 4Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Montpellier, France
  5. 5Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
  6. 6Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium
  7. 7Departments of Pediatrics, Medicine and Molecular Biology and Genetics, and Howard Hughes Medical Institute, John Hopkins University School of Medicine, Baltimore, MD, USA
  8. 8Division of Molecular and Cellular Biochemistry, Department of Biochemistry, University of Oxford, Oxford, UK
  9. 9Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  10. 10Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, USA
  11. 11Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery and Department of Physiology and Biophysics at the Weill Medical College of Cornell University, New York, NY, USA
  12. 12McGill University, Department of Anatomy and Cell Biology and Faculty of Dentistry, Montreal, Canada
  13. 13Center for Human Molecular Genetics, University of Nebraska Medical Center, Omaha, NE, USA
  1. Correspondence to:
 Dr Peter N Robinson
 Institute of Medical Genetics, Charité University Hospital, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany; peter.robinson{at}
  • Received 7 March 2006
  • Accepted 9 March 2006
  • Published Online First 29 March 2006


Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.


  • Published Online First 29 March 2006

  • The authors of this work would like to acknowledge support from Marfan Hilfe (Deutschland) e.V., the Canadian Marfan Association, the National Marfan Foundation (USA), the Deutsche Forschungsgemeinschaft (Grant SFB367-A1), the Canadian Institutes of Health Research (Grant MOP-68836), the Fund for Scientific Research Flanders, the Howard Hughes Medical Institute, National Institutes of Health (AR-41135, AR-049698 and AR-42044), the St Giles Foundation, the James D. Farley Family, the Smilow Center for Marfan Syndrome Research, and the Medical Research Council (G000164)

  • Competing interests: none declared