RESUMO
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 TGFßR2 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-ß 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.
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Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Receptor do Fator de Crescimento Transformador beta Tipo II , Humanos , Masculino , Adulto , Dissecção Aórtica/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Aneurisma da Aorta Torácica/genética , Linhagem , Aneurisma Aórtico/genética , Splicing de RNA/genética , Sítios de Splice de RNA/genética , Predisposição Genética para Doença/genética , Mutação/genéticaRESUMO
INTRODUCTION: Current guidelines recommend patients with thoracic aortic disease (TAD) including inherited aortopathies to avoid heavy exercise. However, evidence supporting the negative advice on exercise is scarce. We aimed to provide an up-to-date systematic review of the available evidence on risks and benefits of exercise and sports participation in TAD patients. Areas covered: A systematic search was performed in Medline, Embase and Web of Science: thoracic aortic aneurysm or thoracic aortic dissection or inheritable aortopathies including Marfan Syndrome (MFS), Loeys-Dietz syndrome, Turner Syndrome, Ehlers-Danlos syndrome, bicuspid aortic valve (BAV) and sports, exercise or athletes. The resulting 1,652 manuscripts were reviewed by two independent observers. Eventually, 26 studies and 12 case-reports were included, reporting on thoracic aortic dimensions in athletes, exercise related acute aortic dissections, and exercise in BAV and MFS patients. Expert opinion: Blood pressure elevation during exercise may be associated with an increased risk of acute aortic dissection; however, no controlled trials have longitudinally evaluated the effect of exercise on survival or the risk of aortic dissection in TAD patients. Mouse-model studies suggest beneficial effects of exercise in the setting of a dilated aorta in MFS. There is a clear need for prospective research in this field.