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We report the clinical presentation and genetic screening of a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. A novel heterozygous variant in a splice acceptor site (c.1600-1G>T) of TGFβR2 gene was identified by using a targeted multi-gene panel analysis. Bioinformatics tools predicted that the c.1600-1G>T variant is pathogenic by altering acceptor splice site at − 1 position affecting pre-mRNA splicing. These data confirm that the diverging splicing in the TGF-β pathway genes may be an important process in aneurismal disease and emphasize the utility of genetic sequencing in the identification of high-risk patients for a more patient's management able to improve outcomes and minimize costs for the care of patients with heritable thoracic aortic aneurysm and dissection. Executive summary Heritable thoracic aortic aneurysms (TAA) refer to a group of genetic connective tissue disorders affecting the aorta, typically asymptomatic, leading to an acute aortic dissection with life-threatening complications including sudden death. Mutations in the genes encoding the TGF-b receptors (TGFBR1 and TGFBR2) have been identified as a cause of familial TAA and dissections. Nevertheless, the effects of individual gene variants are not completely understood. The screening of a targeted multi-gene panel reveals a heterozygous novel variant in the TGFβR2 gene in a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. The novel heterozygous TGFβR2 variant c.1600-1G>T was found within the acceptor splice site of exon 7. Varsome and Franklin database classified the variant as "likely pathogenetic". Splicing evaluation programs predicted that the c.1600-1G>T variant is pathogenic since affects the pre-mRNA splicing by the altering acceptor splice site at − 1 position. Differential splicing is a common feature of TAA formation, and in particular, the diverging splicing in the TGF-β pathway genes may be an important process in aneurismal disease. Utility of genetic screening in the identification of high-risk patients with heritable TAA for a more personalized management pointing at improving outcomes and minimize care costs. [ABSTRACT FROM AUTHOR]

Background: The assessment of Fontan circuit’s flow is traditionally evaluated by multiple through-plane phase-contrast MRI acquisitions (2D flow), while recently, a single volumetric 4D-flow MRI acquisition is emerging as a comprehensive tool for the hemodynamic evaluation in congenital heart diseases. Purpose: To compare 2D and 4D-flow MRI measurements in patients after Fontan palliation and to evaluate parameters affecting potential disagreement. Methods: 39 patients after Fontan palliation (23 males, age 22 ± 11 years) who underwent cardiac MRI with 2D and 4D-flow MRI acquisition were included in the study. In all patients, blood flow quantification in the Fontan circuit and aorta by 2D flow and by 4D flow MRI acquisition blinding to the 2D results was performed. The agreement between 2D and 4D-flow MRI was calculated as the intraclass correlation coefficient (ICC). The mean absolute differences between 4D and 2D flows were analyzed using linear regression models. Results: 4D-flow MRI acquisition time was slightly lower than 2D (7.6 ± 1.8 min vs. 9.4 ± 3.3 min, p = 0.03). Flow was slightly predominant in the right pulmonary artery (58% of total pulmonary flow). Conduit/tunnel-pulmonary arteries flow accounted for 60% of the Fontan circuit. Agreement between 2D and 4D was overall good-to-excellent from ICC: 0.817 95% CI: 0.637–0.907 to 0.932 95% CI: 0.866–0.965. There was no significant influence of evaluated parameters on the agreement on 4D and 2D flow. Conclusions: 4D-flow MRI represents a valid tool in Fontan’s flow quantification. Further larger studies are needed to confirm our results and to evaluate the impact of advanced 4D-flow MRI parameters on the prognostic stratification in patients after Fontan palliation. [ABSTRACT FROM AUTHOR]