Cardiovascular manifestations in men and women carrying a FBN1 mutation.
OBJECTIVE
In patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in the course of the disease. This study evaluates the cardiovascular (CV) risk associated with the discovery of a fibrillin-1 (FBN1) mutation.


RESULTS
A total of 1,013 probands with pathogenic FBN1 mutations were included, among whom 965 patients [median age: 22 years (11-34), male gender 53%] had data suitable for analysis. The percentage of patients with an ascending aortic (AA) dilatation increased steadily with increasing age and reached 96% (95% CI: 94-97%) by 60 years. The presence of aortic events (dissection or prophylactic surgery) was rare before 20 years and then increased progressively, reaching 74% (95% CI: 67-81%) by 60 years. Compared with women, men were at higher risk for AA dilatation [≤ 30 years: 57% (95% CI: 52-63) vs. 50% (95% CI: 45-55), P = 0.0076] and aortic events [≤ 30 years: 21% (95% CI: 17-26) vs. 11% (95% CI: 8-16), P < 0.0001; adjusted HR: 1.4 (1.1-1.8), P = 0.005]. The prevalence of mitral valve (MV) prolapse [≤ 60 years: 77% (95% CI: 72-82)] and MV regurgitation [≤ 60 years: 61% (95% CI: 53-69)] also increased steadily with age, but surgery limited to the MV remained rare [≤ 60 years: 13% (95% CI: 8-21)]. No difference between genders was observed (for all P> 0.20). From 1985 to 2005 the prevalence of AA dilatation remained stable (P for trend = 0.88), whereas the percentage of patients with AA dissection significantly decreased (P for trend = 0.01).


CONCLUSIONS
The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring. Aortic dilatation or dissection should always trigger suspicion of a genetic background leading to thorough examination for extra-aortic features and comprehensive pedigree investigation.
Détaint
Delphine
D
AP-HP, Hôpital Bichat, Consultation pluridisciplinaire Syndrome de Marfan et apparentés, Paris F-75018, France. delphine.detaint@bch.aphp.fr
Faivre
Laurence
L
Collod-Beroud
Gwenaelle
G
Child
Anne H
AH
Loeys
Bart L
BL
Binquet
Christine
C
Gautier
Elodie
E
Arbustini
Eloisa
E
Mayer
Karin
K
Arslan-Kirchner
Mine
M
Stheneur
Chantal
C
Halliday
Dorothy
D
Beroud
Christophe
C
Bonithon-Kopp
Claire
C
Claustres
Mireille
M
Plauchu
Henri
H
Robinson
Peter N
PN
Kiotsekoglou
Anatoli
A
De Backer
Julie
J
Adès
Lesley
L
Francke
Uta
U
De Paepe
Anne
A
Boileau
Catherine
C
Jondeau
Guillaume
G
D000293:Adolescent; D000328:Adult; D000784:Aortic Dissection / Q000235:genetics*; D001014:Aortic Aneurysm / Q000235:genetics*; D002648:Child; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008945:Mitral Valve Prolapse / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines