Contributors: Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC); Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM); Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR); Université Montpellier 1 (UM1)-IFR3; Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Department of Cardiological Sciences; St George's Hospital; Center for Medical Genetics Ghent; Ghent University Hospital; Institute of Genetic Medicine and the Howard Hughes Medical Institute; Johns Hopkins University School of Medicine; Centre for Inherited Cardiovacular Diseases; Foundation IRCCS Policlinico San Matteo; Center for Human Genetics and Laboratory Medicine; Center of Human Genetics and Laboratory Medicine; Institut für Humagenetik; Hannover Medical School Hannover (MHH)-Institut für Humagenetik; Service de pédiatrie, urgences enfants CHU Ambroise-Paré; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré AP-HP; Consultation Marfan; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat; Department of Biochemistry Oxford; University of Oxford Oxford; Service de Génétique; Hôtel Dieu; Institut für Medizinische Genetik; Charité - UniversitätsMedizin = Charité - University Hospital Berlin; Marfan Research Group; Westmead Hospital Sydney; Department of Clinical Genetics; Discipline of Paediatrics and Child Health; The University of Sydney; Department of Genetics Stanford; Stanford Medicine; Stanford University-Stanford University; Service de biochimie, d'hormonologie et de génétique moléculaire CHU Amrboise Paré; This work was supported by a grant from the French ministry of health (PHRC 2004), GIS maladies rares 2004, Bourse de la Socie´te´ Francaise de Cardiologie, Fédération Franc¸aise 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.
نبذة مختصرة : International audience ; 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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