RT Journal Article
SR Electronic
T1 Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 384
OP 390
DO 10.1136/jmg.2007.056382
VO 45
IS 6
A1 L Faivre
A1 G Collod-Beroud
A1 A Child
A1 B Callewaert
A1 B L Loeys
A1 C Binquet
A1 E Gautier
A1 E Arbustini
A1 K Mayer
A1 M Arslan-Kirchner
A1 C Stheneur
A1 A Kiotsekoglou
A1 P Comeglio
A1 N Marziliano
A1 D Halliday
A1 C Beroud
A1 C Bonithon-Kopp
A1 M Claustres
A1 H Plauchu
A1 P N Robinson
A1 L Adès
A1 J De Backer
A1 P Coucke
A1 U Francke
A1 A De Paepe
A1 C Boileau
A1 G Jondeau
YR 2008
UL http://jmg.bmj.com/content/45/6/384.abstract
AB 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.