Match!

International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results of the MAC (Montalcino Aortic Consortium)

Published on Dec 1, 2016in Circulation-cardiovascular Genetics4.86
· DOI :10.1161/CIRCGENETICS.116.001485
Guillaume Jondeau51
Estimated H-index: 51
(University of Paris),
Jacques Ropers4
Estimated H-index: 4
+ 25 AuthorsDianna M. Milewicz56
Estimated H-index: 56
(University of Texas at Austin)
Cite
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. Methods and 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.
  • References (0)
  • Citations (23)
Cite
References0
Newest
Cited By23
Newest
Published on Feb 11, 2019in Genetics in Medicine8.68
Pauline Arnaud4
Estimated H-index: 4
(Paris Diderot University),
Nadine Hanna10
Estimated H-index: 10
(Paris Diderot University)
+ 19 AuthorsThomas Edouard7
Estimated H-index: 7
Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients and the contribution of each gene in nshTAAD. Two hundred twenty-six consecutive nshTAAD probands, either young (<45 years) sporadic or familial case...
Published on Apr 1, 2019in Journal of Cardiology2.29
Norifumi Takeda13
Estimated H-index: 13
(UTokyo: University of Tokyo),
Norifumi Takeda9
Estimated H-index: 9
(UTokyo: University of Tokyo),
Issei Komuro88
Estimated H-index: 88
(UTokyo: University of Tokyo)
Abstract Recent advances in DNA sequencing technology have identified several causative genes for hereditary thoracic aortic aneurysms and dissections (TAADs), including Marfan syndrome (MFS), Loeys–Dietz syndrome, vascular Ehlers–Danlos syndrome, and familial non-syndromic TAADs. Syndromic TAADs are typically caused by pathogenic variants in the transforming growth factor-β signal and extracellular matrix-related genes (e.g. FBN1 , TGFBR1 , TGFBR2 , SMAD3 , TGFB2 , and COL3A1 ). On the other ha...
Published on Jun 1, 2019in Biochemical Pharmacology4.83
Andreas H. Wagner13
Estimated H-index: 13
(Heidelberg University),
Marcin Zaradzki3
Estimated H-index: 3
(University Hospital Heidelberg)
+ 3 AuthorsK. Kallenbach
Abstract Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the fibrillin-1 gene. Acute aortic dissection is the leading cause of death in patients suffering from MFS and consequence of medial degeneration and aneurysm formation. In addition to its structural function in the formation of elastic fibers, fibrillin has a major role in keeping maintaining transforming growth factor β (TGF-β) in an inactive form. Dysfunctional fibrillin increases TGF-β bioavailabi...
Adam J. Brownstein4
Estimated H-index: 4
(Yale University),
Bulat A. Ziganshin14
Estimated H-index: 14
(Yale University),
John A. Elefteriades54
Estimated H-index: 54
(Yale University)
Thoracic aortic aneurysm (TAA), a typically silent but frequently lethal disease, is strongly influenced by underlying genetics. Approximately 30 genes have been associated with syndromic and non-syndromic familial thoracic aortic aneurysm and dissection (TAAD) to date. An estimated 30% of patients with non-syndromic familial TAAD, which is typically inherited in an autosomal dominant manner, have a mutation in one of these genes. The underlying genetic mutation helps predict patients’ clinical ...
Published on Apr 1, 2019in Journal of Medical Genetics5.90
Ellen M. Hostetler6
Estimated H-index: 6
(University of Texas Health Science Center at San Antonio),
Ellen S. Regalado24
Estimated H-index: 24
(University of Texas Health Science Center at San Antonio)
+ 14 AuthorsStephanie Wallace3
Estimated H-index: 3
(University of Texas Health Science Center at San Antonio)
Background Pathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3 variants. Methods Aortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 ...
Muhammad Aftab8
Estimated H-index: 8
(University of Colorado Denver),
Frank Cikach10
Estimated H-index: 10
(Cleveland Clinic)
+ 5 AuthorsLars G. Svensson75
Estimated H-index: 75
(Cleveland Clinic)
Abstract Objectives Loeys-Dietz syndrome (LDS) is an aggressive connective tissue disorder associated with increased risk of aortic dissection and aneurysm rupture at an early age and smaller aortic diameters. We report our experience with LDS to better understand its natural history and treatment outcomes and help establish treatment guidelines. Methods We retrospectively reviewed all patients with LDS who underwent medical or surgical treatment at Cleveland Clinic before April 27, 2017. Primar...
Published on Jan 1, 2019in SAGE open medical case reports
Homira Bashari (Royal Women's Hospital), Alexandra Brooks (Royal Women's Hospital)+ 2 AuthorsD. Zentner Fracp7
Estimated H-index: 7
(Royal Melbourne Hospital)
Loeys–Dietz syndrome is a rare autosomal dominant connective tissue disorder. Pregnant women with Loeys–Dietz syndrome are at increased risk of serious vascular and visceral complications, includin...
Published on Jan 1, 2019
Ayman Saeyeldin3
Estimated H-index: 3
(Yale University),
Camilo A. Velasquez3
Estimated H-index: 3
(Yale University)
+ 4 AuthorsJohn A. Elefteriades54
Estimated H-index: 54
(Yale University)
Thoracic aortic aneurysm (TAA) is an increasingly recognized condition that is often diagnosed incidentally. This review discusses ten of the most relevant epidemiological and clinical secrets of this disease; (1) the difference in pathogenesis between ascending and descending TAAs. TAAs at these two sites act as different diseases, which is related to the different embryologic origins of the ascending and descending aorta. (2) The familial pattern and genetics of thoracic aneurysms. Syndromic T...
Published on Jan 1, 2019in Genetics in Medicine8.68
Stephanie Wallace3
Estimated H-index: 3
(University of Texas Health Science Center at Houston),
Ellen S. Regalado24
Estimated H-index: 24
(University of Texas Health Science Center at Houston)
+ 17 AuthorsCatherine Boileau55
Estimated H-index: 55
(Paris Diderot University)
Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm rep...
View next paperAneurysm Syndromes Caused by Mutations in the TGF-β Receptor