Aortic and arterial manifestations and clinical features in TGFB3 -related heritable thoracic aortic disease: results from the Montalcino Aortic Consortium.

Autor:	Lim MS; Cardiovascular Division, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA., Guo DC; Department of Internal Medicine, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA., Velasco Torrez W; Department of Internal Medicine, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA., Lai A; Cardiovascular Division, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA., Schweber J; The Hospital for Sick Children, Toronto, Ontario, Canada., Garg N; Department of Paediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA., Fleischer J; Department of Paediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA., Boileau C; Département de Génétique, Universite Paris Cite, Paris, France., De Backer J; Division of Cardiology and Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Evangelista A; Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain., Jondeau G; CRMR Marfan et apparentés, APHP, Hopital Bichat, Université Paris Cité, Paris, France., Le Goff C; Laboratory of Vascular Translational Science, Bichat Hospital, Université Paris Cité and Université Sorbonne Paris Nord, Paris, France., Milleron O; Centre de Référence Maladies Rares Syndrome de Marfan et apparentés, Hôpital Bichat, Paris, France., Muiño-Mosquera L; Department of Paediatrics, Division of Paediatric Cardiology and Center for Medical Genetics, Universitair Ziekenhuis Gent, Ghent, Belgium., Morris S; Division of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA., Ouzounian M; Cardiothoracic Surgery, University of Toronto, Toronto, Ontario, Canada., Cervi E; 14Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK., Marcadier J; Department of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta, Canada., Caffarelli A; Department of Cardiac Surgery, Hoag Memorial Presbyterian Hospital, Newport Beach, California, USA., Shalhub S; Division of Vascular Surgery, University of Oregon Health Sciences, Portland, Oregon, USA., Pyeritz R; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Yetman A; Department of Paediatrics, Division of Cardiology, University of Nebraska, Children's Hospital, Omaha, Nebraska, USA., Milewicz D; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Braverman AC; Cardiovascular Division, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA abraverm@wustl.edu.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI:	10.1136/jmg-2024-110251
Abstrakt:	Background: Pathogenic variants in TGFB3 may lead to a syndromic genetic aortopathy. Heritable thoracic aortic disease (HTAD) and arterial events may occur in TGFB3 -related disease but there are limited outcomes data on vascular events in this condition. Methods: Clinical data, phenotypical features and aortic outcomes in individuals with pathogenic/likely pathogenic (P/LP) TGFB3 variants enrolled in the Montalcino Aortic Consortium registry were reviewed. Results: 34 individuals (56% male, median age 42 years, IQR 17-49, range 3-74 years) with P/LP TGFB3 variants were studied. Craniofacial, cutaneous and musculoskeletal features seen in Loeys-Dietz syndrome were variably present. Extra-aortic cardiovascular features included arterial tortuosity (25%), extra-aortic arterial aneurysms (6%) and mitral valve prolapse (21%).Aortic dilation (Z-Score>2) was present in 10 individuals (29%) and aortic dissection occurred in 2 (6%). Type A aortic dissection occurred in two patients (aged between 55 years and 60 years), and one of these patients experienced a type B aortic dissection 6 years later. Seven adults (median age 62 years, range 32-69 years) with aortic root dilation (41-49 mm) are being followed. No patients have undergone prophylactic aortic surgery. Twenty-five per cent of children have aortic dilation. Sixty-eight per cent of the entire cohort remains free of aortic disease. No deaths have occurred. Conclusions: TGFB3 -related HTAD is characterised by late-onset and less penetrant thoracic aortic and arterial disease compared with other transforming growth factor β HTAD. Based on our data, a larger aortic size threshold for prophylactic aortic surgery is appropriate in patients with TGFB3 -related HTAD compared with HTAD due to TGFBR1 or TGFBR2 variants. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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