2008 Barcelona - European Society of Human Genetics

Clinical genetics
CM in monozygotic twins where only one is affected, suggesting that
M-CM is due to a post-zygotic event .
P01.316
study of the aortic risk associated with FBN mutations from
an international study of 1013 patients with marfan syndrome or
related type I fibrillinopathy
L. Faivre 1 , G. Collod-Beroud 2 , B. Loeys 3 , A. Child 4 , C. Binquet 5 , E. Gautier 5 , B.
Callaewert 3 , E. Arbustini 6 , K. Mayer 7 , M. Arslan-Kirchner 8 , C. Beroud 9 , M. Claustres
9 , C. Bonithon-Kopp 5 , L. Ades 10 , J. De Backer 3 , P. Coucke 3 , U. Francke 11 , A.
De Paepe 3 , C. Boileau 12 , G. Jondeau 13 ;
1 Departement de Genetique, Dijon, France, 2 INSERM, U827, Montpellier,
France, 3 Center for Medical Genetics, Ghent, Belgium, 4 4 Department of Cardiological
Sciences, St. George’s Hospital, London, United Kingdom, 5 Centre
d’investigation clinique – épidémiologie clinique/essais cliniques, Dijon, France,
6 Molecular Diagnostic Unit, Policlinico San Matteo, Pavia, Italy, 7 Center for
Human Genetics and Laboratory Medicine, Martinsried, Germany, 8 Institut für
Humangenetik, Hannover, Germany, 9 Laboratoire de Génétique Moléculaire,
Hôpital Arnault de Villeneuve, Montpellier, France, 10 Marfan Research Group,
The Children’s Hospital at Westmead, Sidney, Australia, 11 Departments of Genetics
and Pediatrics, Stanford, CA, United States, 12 Laboratoire de Génétique
moléculaire, Hôpital Ambroise Paré, Boulogne, France, 13 Centre de Référence
Maladie de Marfan, Hôpital Bichat, Paris, France.
In order to better describe the aortic risk associated with mutations
in the FBN1 gene, we took advantage of a series of 1013 genotyped
probants carrying Marfan syndrome or another type I fibrillinopathy,
recruited for a genotype-phenotype correlation study . At 40 years
of age, the cumulative probability of presenting an ascending aortic
dilatation (AAD) was 75% (95%-CI=72%-78%), 26% (95%-CI=22%-
31%) for ascending aortic dissection and 41% (95%-CI=36%-46%)
for cardiac surgery . The cumulative probability of presenting AAD
was higher in males than in females (80% [95%-CI=76%-83%] at 40
years of age in males versus 70% [95%-CI=65%-75%] in females;
p=0 .0036) . An higher risk of aortic surgery was also observed in males
(46% [95%-CI=39%-52%] versus 34% [95%-CI=27%-42%] in females
; p=0 .0002) . The study of the paediatric cohort (n=320) showed that
aortic complications remained an exception, with a 1% risk of aortic
dissection and a 5% risk of aortic surgery at 10 years of age . Adult
patients diagnosed during childhood had a higher risk of developing
AAD (81% [95%-CI=73%-88%] at 40 years of age) than patients diagnosed
in adulthood (65% [95%-CI=60%-69%], p