title: International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results of the MAC (Montalcino Aortic Consortium).
abstract: BACKGROUND
  The natural history of aortic diseases in patients with TGFBR1 or TGFBR2 mutations reported by different investigators has varied greatly. In particular, the current recommendations for the timing of surgical repair of the aortic root aneurysms may be overly aggressive.
  
  
  RESULTS
  The Montalcino Aortic Consortium, which includes 15 centers worldwide that specialize in heritable thoracic aortic diseases, was used to gather data on 441 patients from 228 families, with 176 cases harboring a mutation in TGBR1 and 265 in TGFBR2. Patients harboring a TGFBR1 mutation have similar survival rates (80% survival at 60 years), aortic risk (23% aortic dissection and 18% preventive aortic surgery), and prevalence of extra-aortic features (29% hypertelorism, 53% cervical arterial tortuosity, and 27% wide scars) when compared with patients harboring a TGFBR2 mutation. However, TGFBR1 males had a greater aortic risk than females, whereas TGFBR2 males and females had a similar aortic risk. Additionally, aortic root diameter prior to or at the time of type A aortic dissection tended to be smaller in patients carrying a TGFBR2 mutation and was ≤45 mm in 6 women with TGFBR2 mutations, presenting with marked systemic features and low body surface area. Aortic dissection was observed in 1.6% of pregnancies.
  
  
  CONCLUSIONS
  Patients with TGFBR1 or TGFBR2 mutations show the same prevalence of systemic features and the same global survival. Preventive aortic surgery at a diameter of 45 mm, lowered toward 40 in females with low body surface area, TGFBR2 mutation, and severe extra-aortic features may be considered.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Jacques
authors.initials: J
authors.lastname: Ropers
authors.forename: Ellen
authors.initials: E
authors.lastname: Regalado
authors.forename: Alan
authors.initials: A
authors.lastname: Braverman
authors.forename: Arturo
authors.initials: A
authors.lastname: Evangelista
authors.forename: Guisela
authors.initials: G
authors.lastname: Teixedo
authors.forename: Julie
authors.initials: J
authors.lastname: De Backer
authors.forename: Laura
authors.initials: L
authors.lastname: Muiño-Mosquera
authors.forename: Sophie
authors.initials: S
authors.lastname: Naudion
authors.forename: Cecile
authors.initials: C
authors.lastname: Zordan
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morisaki
authors.forename: Hiroto
authors.initials: H
authors.lastname: Morisaki
authors.forename: Yskert
authors.initials: Y
authors.lastname: Von Kodolitsch
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupuis-Girod
authors.forename: Shaine A
authors.initials: SA
authors.lastname: Morris
authors.forename: Richmond
authors.initials: R
authors.lastname: Jeremy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Adès
authors.forename: Madhura
authors.initials: M
authors.lastname: Bakshi
authors.forename: Katherine
authors.initials: K
authors.lastname: Holman
authors.forename: Scott
authors.initials: S
authors.lastname: LeMaire
authors.forename: Olivier
authors.initials: O
authors.lastname: Milleron
authors.forename: Maud
authors.initials: M
authors.lastname: Langeois
authors.forename: Myrtille
authors.initials: M
authors.lastname: Spentchian
authors.forename: Melodie
authors.initials: M
authors.lastname: Aubart
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Reed
authors.initials: R
authors.lastname: Pyeritz
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000601:surgery; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D001315:Australia / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015995:Prevalence; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014656:Vascular Surgical Procedures
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human
keywords: Marfan syndrome; acute aortic dissection gene; aneurysm; aortic disease; aortic dissection; aortic surgery; diagnostics; genetics; human; peripheral vascular disease; sex differences