Challenges of Managing Non-rheumatic Aortic Valve Disorder in a Genetically Susceptible Woman

• Published in: Curēus (Palo Alto, CA) Vol. 15; no. 4; p. e37998
• Main Authors: Vuong, Stephanie, Hollingworth, Alexzandra
• Format: Journal Article
• Language: English
• Published: United States Cureus Inc 22.04.2023; Cureus
• Subjects: Antibiotics; Aortic aneurysms; Aortic stenosis; Auscultation; Blood; Cardiac/Thoracic/Vascular Surgery; Cardiology; Cell growth; Congenital diseases; Coronary vessels; Cytokines; Endocarditis; Genetics; Laboratories; Morphology; Mutation; Pain; Proteins; Surgery; Tomography; aortic valve insufficiency; cardio vascular disease; aortic diseases; cardiovascular genetics; tgf-β1
• ISSN: 2168-8184; 2168-8184
• DOI: 10.7759/cureus.37998

In this case report, we investigated the potential link between SMAD3/transforming growth factor β (TGF-β) pathway dysregulation and aortic valvular disease. We report a middle-aged female, heterozygous for the R18W novel variant of the SMAD3 gene, with a history of an aortic valve disorder and three aortic valve replacements in a span of 15 years. The patient neither has a history of congenital connective tissue disorders nor any known congenital valvular defects. The patient had genetic testing for thoracic aortic aneurysm and dissection (TAAD)/Marfan syndrome/related disorders. She was found to be heterozygous for the p.Arg18Trp (R18W) protein variant of the SMAD3 gene (chromosome position 15:67430416), coding DNA c.52 C>T. Members of the transforming growth factor β (TGF-β) family and their downstream signaling proteins, including SMAD, are important for establishing proper embryogenic development and maintaining adult tissue homeostasis. Investigating the disturbances within the TGF-β signaling pathways may provide insightful knowledge of how genetic factors can cause structural and functional valvular defects.