title: Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders.
abstract: BACKGROUND
  TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear.
  
  
  RESULTS
  Clinical features and outcomes of 71 patients with a TGFBR2 mutation (TGFBR2 group) were compared with 50 age- and sex-matched unaffected family members (control subjects) and 243 patients harboring FBN1 mutations (FBN1 group). Aortic dilatation was present in a similar proportion of patients in both the TGFBR2 and FBN1 groups (78% versus 79%, respectively) but was highly variable. The incidence and average age for thoracic aortic surgery (31% versus 27% and 35+/-16 versus 39+/-13 years, respectively) and aortic dissection (14% versus 10% and 38+/-12 versus 39+/-9 years) were also similar in the 2 groups. Mitral valve involvement (myxomatous, prolapse, mitral regurgitation) was less frequent in the TGFBR2 than in the FBN1 group (all P<0.05). Aortic dilatation, dissection, or sudden death was the index event leading to genetic diagnosis in 65% of families with TGFBR2 mutations, versus 32% with FBN1 mutations (P=0.002). The rate of death was greater in TGFBR2 families before diagnosis but similar once the disease had been recognized. Most pregnancies were uneventful (without death or aortic dissection) in both TGFBR2 and FBN1 families (38 of 39 versus 213 of 217; P=1). Seven patients (10%) with a TGFBR2 mutation fulfilled international criteria for Marfan syndrome, 3 of whom presented with features specific for Loeys-Dietz syndrome.
  
  
  CONCLUSIONS
  Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations. Prognosis depends on clinical disease expression and treatment rather than simply the presence of a TGFBR2 gene mutation.
authors.affiliation: Centre de Référence pour le Syndrome de Marfan et Apparentés, Hôpital Bichat, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Attias
authors.forename: Chantal
authors.initials: C
authors.lastname: Stheneur
authors.forename: Carine
authors.initials: C
authors.lastname: Roy
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Collod-Béroud
authors.forename: Delphine
authors.initials: D
authors.lastname: Detaint
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.forename: Laurence
authors.initials: L
authors.lastname: Cohen
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Franck
authors.initials: F
authors.lastname: Iserin
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Henri
authors.initials: H
authors.lastname: Plauchu
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Annick
authors.initials: A
authors.lastname: Rossi
authors.forename: Daniel
authors.initials: D
authors.lastname: Sidi
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
mesh_terms: D000293:Adolescent; D000328:Adult; D000784:Aortic Dissection / Q000453:epidemiology / Q000235:genetics; D001014:Aortic Aneurysm / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000453:epidemiology / Q000235:genetics; D008945:Mitral Valve Prolapse / Q000453:epidemiology / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines