Journal Article

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

Boileau, Catherine, Milleron, Olivier, Caffarelli, Anthony, Evangelista, Artur, Cervi, Elena, Shalhub, Sherene, Milewicz, Dianna, Guo, Dong-Chuan, Fleischer, Julie, Yetman, Angela, Lim, Michelle Su-Anne, Muiño-Mosquera, Laura, Morris, Shaine, Garg, Nikita, Velasco Torrez, Walter, Jondeau, Guillaume, Marcadier, Julien, De Backer, Julie, Pyeritz, Reed, Lai, Andrew, Schweber, Jonathan, Le Goff, Carine, Ouzounian, Maral, Braverman, Alan C

2025

Overview

BackgroundPathogenic 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.MethodsClinical 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.Results34 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.ConclusionsTGFB3-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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: Adolescent / Adult / Age / Aged / Aneurysm / Aorta, Thoracic - pathology / Aortic Aneurysm, Thoracic - genetics / Aortic aneurysms / Aortic Diseases - genetics / Aortic Diseases - pathology / Aortic dissection / Cardiovascular Diseases / Child / Child, Preschool / Consortia / Coronary vessels / Disease / Dissection / Doppler effect / Female / Females / Genetic Predisposition to Disease / Growth factors / Humans / Loeys-Dietz Syndrome - genetics / Loeys-Dietz Syndrome - pathology / Male / Marfan syndrome / Medical imaging / Middle Aged / Mitral valve / Patients / Phenotype / Phenotypes / Standard scores / Surgery / Surveillance / Thorax / Transforming Growth Factor beta3 - genetics / Transforming growth factor-b / Vascular Diseases / Young Adult