title: Heterogeneity of aortic disease severity in patients with Loeys-Dietz syndrome.
abstract: OBJECTIVE
  This study aimed to determine aortic disease severity in patients with Loeys-Dietz syndrome (LDS).
  
  
  METHODS
  Thirty-three patients with LDS diagnosed and followed up at our unit were included. After reviewing all family trees, 25 deceased family members with clear clinical suspicion of having had LDS were also included. Clinical presentation, aortic dilation rate by echocardiography and age at aortic surgery, dissection or death were determined.
  
  
  RESULTS
  Median aortic diameter at diagnosis was 36 mm, 43% of the patients aged >40 years had a z-score <2. Median aortic root dilation rate was 0.67 mm/year (maximum 2.0 mm/year) over a median follow-up of 2 years (IQR 1.0-4.0). In the global cohort, 31/58 patients reached a clinical endpoint; 19% death, median age: 52 years; 14% dissection, median age: 36 years; 21% aortic surgery, median age: 53 years. As expected, probands had a higher z-score (2.9 vs 1.5, p=0.019) and more often required aortic surgery (33.4% vs 18.2%, p=0.035) compared with family members. TGFBR2 carriers had a higher z-score compared with TGFBR1 carriers (3.2 vs 1.5, p=0.034) and younger age at aortic surgery (HR 4.9, 95% CI 1.5 to 123, p=0.026). Craniofacial severity index was inversely correlated with age at first event (r=-0.765, p=0.045).
  
  
  CONCLUSIONS
  Although paediatric patients were not properly represented in our cohort, our patients with LDS presented a significant heterogeneity in the severity of aortic disease with large intrafamilial and interfamilial variability, aortic root aneurysm were less frequent and aortic complications less premature than previously depicted. Furthermore, aortic dilation rate was similar to that reported in Marfan syndrome and aortic root diameters appear to be larger in TGFBR2 carriers.
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Gisela
authors: http://orcid.org/0000-0003-4714-2420
authors: G
authors: Teixidó-Tura
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors: Romy
authors: http://orcid.org/0000-0002-2260-2753
authors: R
authors: Franken
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Valentina
authors: V
authors: Galuppo
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Laura
authors: L
authors: Gutiérrez García-Moreno
authors: Servei de Genètica, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Mar
authors: M
authors: Borregan
authors: Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors: Barbara J M
authors: BJ
authors: Mulder
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: David
authors: D
authors: García-Dorado
authors: Servei de Cardiologia, Unitat de Marfan, Hospital Universitari, Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Artur
authors: A
authors: Evangelista
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000784:Aortic Dissection / Q000235:genetics / Q000473:pathology; D001014:Aortic Aneurysm / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics; D004108:Dilatation, Pathologic / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D055947:Loeys-Dietz Syndrome / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; 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; D012720:Severity of Illness Index; D055815:Young Adult
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