Chapter 2 – Cardiovascular Phenotype of Aneurysms-Osteoarthritis Syndrome

Abstract Recently, pathogenic SMAD3 variants were found to cause Aneurysms-Osteoarthritis syndrome (AOS). AOS is inherited as an autosomal dominant disorder and is found to be responsible for 2% of familial thoracic aortic aneurysms and dissections. Aneurysms, dissections, and tortuosity throughout the arterial tree are the main cardiovascular features. Aortic aneurysms are most commonly located in the aortic root at the level of the sinus of Valsalva. The progression rate of the aortic dilatation is variable but can be rapid and unpredictable. Aortic dissections most commonly occur in the fourth decade of life, sometimes in relatively mildly dilated aortas. Other cardiac features include mitral valve prolapse and congenital heart defects. This chapter describes in detail all the cardiovascular features associated with AOS.