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Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands
  1. L Faivre1,2,
  2. G Collod-Beroud3,4,
  3. A Child5,
  4. B Callewaert6,
  5. B L Loeys6,7,
  6. C Binquet2,8,
  7. E Gautier2,8,
  8. E Arbustini9,
  9. K Mayer10,
  10. M Arslan-Kirchner11,
  11. C Stheneur12,
  12. A Kiotsekoglou5,
  13. P Comeglio5,
  14. N Marziliano9,
  15. D Halliday13,
  16. C Beroud3,4,14,
  17. C Bonithon-Kopp2,8,
  18. M Claustres3,4,14,
  19. H Plauchu15,
  20. P N Robinson16,
  21. L Adès17,18,19,
  22. J De Backer6,
  23. P Coucke6,
  24. U Francke20,
  25. A De Paepe6,
  26. C Boileau21,
  27. G Jondeau22
  1. 1
    CHU Dijon, Centre de Génétique, Dijon, France
  2. 2
    CHU, Dijon, Centre d’investigation clinique – épidémiologie clinique/essais cliniques, Dijon, France
  3. 3
    INSERM, U827, Montpellier, France
  4. 4
    Université Montpellier1, Montpellier, France
  5. 5
    Department of Cardiological Sciences, St George’s Hospital, London, UK
  6. 6
    Center for Medical Genetics, Ghent University Hospital, Belgium
  7. 7
    Institute of Genetic Medicine and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, USA
  8. 8
    INSERM, CIE1, Dijon, France
  9. 9
    Centre for Inherited Cardiovascular Diseases, Foundation IRCCS Policlinico San Matteo, Pavia, Italy
  10. 10
    Center for Human Genetics and Laboratory Medicine, Martinsried, Germany
  11. 11
    Institute of Human Genetics, Hannover Medical School, Hannover, Germany
  12. 12
    AP-HP, Hôpital Ambroise Paré, Service de Pédiatrie, Boulogne, France
  13. 13
    Department of Biochemistry, University of Oxford, UK
  14. 14
    CHU Montpellier, Hôpital Arnault de Villeneuve, Laboratoire de Génétique Moléculaire, Montpellier, France
  15. 15
    Hôtel Dieu, Service de Génétique, Lyon, France
  16. 16
    Institut für Medizinische Genetik, Universitätsmedizin Charité, Berlin, Germany
  17. 17
    Marfan Research Group, The Children’s Hospital at Westmead, Sydney, Australia
  18. 18
    Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia
  19. 19
    Department of Clinical Genetics, The Children’s Hospital at Westmead, Sydney, Australia
  20. 20
    Departments of Genetics and Pediatrics, Stanford University Medical Center, USA
  21. 21
    AP-HP, Hôpital Ambroise Paré, Laboratoire de Génétique moléculaire, Boulogne, France
  22. 22
    AP-HP, Hôpital Bichat, Consultation pluridisciplinaire Marfan, Paris, France
  1. Dr L Faivre, Centre de Génétique, Hôpital d’Enfants, 10, bd Maréchal De Lattre de Tassigny, 21034 Dijon, France; laurence.faivre{at}


Background: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening.

Methods: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling “clinical” criteria. In patients with unfulfilled “clinical” criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the “clinical” international criteria.

Results: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled “clinical criteria” when compared to the Marfan syndrome group (44% vs 73% at 40 years, p<0.001), but the lifelong risk for ascending aortic dissection or surgery was not significantly different in both groups.

Conclusions: Because of its implications for aortic follow-up, FBN1 molecular analysis is recommended in newly suspected MFS when two systems are involved with at least one major system affected. This is of utmost importance in patients without aortic dilatation and in children.

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  • Competing interests: None declared.

  • Funding: This work was supported by a grant from the French ministry of health (PHRC 2004), GIS maladies rares 2004, Bourse de la Société Francaise de Cardiologie, Fédération Française de Cardiologie 2005, and ANR-05-PCOD-014. BC and BL are respectively a research fellow and a senior clinical investigator of the Fund for Scientific Research – Flanders. AC and PC thank the Marfan Trust, and the Bluff Field Charitable Fund for support.

  • Patient consent: Patients gave consent for FBN1 mutation analysis. This study is a retrospective analysis and does not provide personal information regarding patients.