Current understanding of the genetics of thoracic aortic disease

Abstract

Thoracic aortic dissection is a feared, highly lethal condition most commonly developing from aneurysmal dilation of the thoracic aorta. Elective prophylactic replacement of thoracic aortic aneurysms dramatically mitigates this risk. However, diagnosis of a thoracic aortic aneurysm can be challenging. Thoracic aortic disease - horacic aortic aneurysm and dissection (TAAD) - can be sporadic or heritable. Patients with syndromic heritable TAAD present with classic phenotype and clinical features correlating to their disease. In contrast, patients with non-syndromic heritable disease are harder to diagnose due to their lack of defining uniform phenotypes. Recent advances in genomics have begun to elucidate the genetic underpinnings of non-syndromic TAAD (ns-TAAD) for better understanding this complex disease and improve diagnosis and management. Herein, we review the foundation of knowledge in ns-TAAD heritability and key research studies identifying gene mutations in vascular smooth muscle cells, the extracellular matrix, and TGF-beta signaling present in ns-TAAD. We summarize the current guidelines for the diagnosis, screening, and surgical management of ns-TAAD including recommendations for genetic testing of high-risk individuals. Finally, we highlight areas of future research that will continue to advance our understanding of the complex genetic and epigenetic factors in TAAD.