The revised Ghent nosology for the Marfan syndrome

Bart L Loeys (1) , Harry C Dietz (2) , Alan C Braverman (3) , Bert L Callewaert (1) , Julie de Backer (1) , Richard B Devereux (4) , Yvonne Hilhorst-Hofstee (5) , Guillaume Jondeau (6) , Laurence Faivre (7) , Dianna M Milewicz (8) , Reed E Pyeritz (9) , Paul Sponseller (10) , Paul Wordsworth (11) , Anne M de Paepe (1)

1 Center for Medical Genetics [Ghent]
2 McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, Baltimore, MD
3 Department of Cardiology [Saint-Louis]
4 Weill Medical College of Cornell University [New York]
5 Center for Human and Clinical Genetics
6 CRMR Marfan - Centre de Référence Maladies Rares Syndrome de Marfan et Maladies Apparentées [AP-HP]
7 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
8 Department of Medical Genetics, University of Texas Medical School, Houston
9 Department of Medical Genetics, University of Pennsylvania, Philadelphia
10 Department of Orthopedics, Johns Hopkins University, Baltimore
11 Clinical Rheumatology, Nuffield Orthopeadic Center, Oxford

The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counseling. These Ghent criteria have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, or are not applicable in children or necessitate specialized investigations. The recognition of variable clinical expression and recently extended differential diagnosis are further confounding accurate diagnostic decision making. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurym and ectopia lentis are the cardinal clinical features. In absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of any of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines.

Mots clés: Cardiovascular Medicine; Diagnostics

Bart L Loeys, Harry C Dietz, Alan C Braverman, Bert L Callewaert, Julie de Backer, et al.. The revised Ghent nosology for the Marfan syndrome. Journal of Medical Genetics, 2010, 47 (7), pp.476. ⟨10.1136/jmg.2009.072785⟩. ⟨hal-00557373⟩