title: Cardiovascular manifestations in men and women carrying a FBN1 mutation.
abstract: 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.
authors: AP-HP, Hôpital Bichat, Consultation pluridisciplinaire Syndrome de Marfan et apparentés, Paris F-75018, France. delphine.detaint@bch.aphp.fr
authors: Delphine
authors: D
authors: Détaint
authors: Laurence
authors: L
authors: Faivre
authors: Gwenaelle
authors: G
authors: Collod-Beroud
authors: Anne H
authors: AH
authors: Child
authors: Bart L
authors: BL
authors: Loeys
authors: Christine
authors: C
authors: Binquet
authors: Elodie
authors: E
authors: Gautier
authors: Eloisa
authors: E
authors: Arbustini
authors: Karin
authors: K
authors: Mayer
authors: Mine
authors: M
authors: Arslan-Kirchner
authors: Chantal
authors: C
authors: Stheneur
authors: Dorothy
authors: D
authors: Halliday
authors: Christophe
authors: C
authors: Beroud
authors: Claire
authors: C
authors: Bonithon-Kopp
authors: Mireille
authors: M
authors: Claustres
authors: Henri
authors: H
authors: Plauchu
authors: Peter N
authors: PN
authors: Robinson
authors: Anatoli
authors: A
authors: Kiotsekoglou
authors: Julie
authors: J
authors: De Backer
authors: Lesley
authors: L
authors: Adès
authors: Uta
authors: U
authors: Francke
authors: Anne
authors: A
authors: De Paepe
authors: Catherine
authors: C
authors: Boileau
authors: Guillaume
authors: G
authors: Jondeau
mesh_terms: 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
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines