Update on the molecular landscape of thoracic aortic aneurysmal disease

Thoracic aortic aneurysms and dissections (TAADs) are a major health problem in the Western population. This review summarises recent discoveries in the genetic landscape of TAAD disease, discusses current challenges in clinical practice, and describes the molecular road ahead in TAAD research. Disorders, in which aneurysmal disease is not observed in the thoracic aorta, are not discussed.

Current gene discovery studies have pinpointed about 40 genes associated with TAAD risk, accounting for about 30% of the patients. Importantly, novel genes, and their subsequent functional characterisation, have expanded the knowledge on disease-related pathways providing crucial information on key elements in this disease, and it pinpoints new therapeutic targets. Moreover, current molecular evidence also suggests the existence of less monogenic nature of TAAD disease, in which the presentation of a diseased patient is most likely influenced by a multitude of genetic and environmental factors.

Ongoing molecular genetic research continues to expand our understanding on the pathomechanisms underlying TAAD disease in order to improve molecular diagnosis, optimise risk stratification, advance therapeutic strategies and facilitate counselling of TAAD patients and their families.