How can genetic diagnosis inform the decision of when to operate?

Abstract

Genetic discovery for heritable thoracic aortic disease (HTAD) has been progressing at a brisk pace. Surgical management of thoracic aortic aneurysms and dissections has become more personalized, with genetic factors increasingly informing the decision of when to operate on patients. An improved understanding of genotype-phenotype correlations in patients with HTAD will ultimately lead to gene- and mutation-specific recommendations for surgical repair. Until more robust data from larger cohorts can inform our decisions, patients with HTAD should be seen by an aortic specialist for a tailored approach to elective surgical repair.

Keywords: Thoracic aortic aneurysm; aortic dissection; genetics; surgery.

Figure 1

Classification of thoracic aortic aneurysms. BAV/TAA, bicuspid aortic valve-associated thoracic aortic aneurysm.

Figure 2

Schematic representation of the 2010 revised Ghent criteria for the diagnosis of Marfan syndrome. For details regarding systemic scores, definitions of other criteria, and caveats, see (13).

Figure 3

Simplified schematic illustration of aortic root/ascending aortic diameter thresholds for elective surgical repair. Individual genes and conditions are paired with one of four diameter thresholds above which elective repair is generally recommended: (I) ≥4.0 cm; (II) ≥4.5 cm; (III) ≥5.0 cm; and (IV) ≥5.5 cm. Factors that influence the decision about where to set a threshold for individual patients are listed. Rapid expansion is an increase in aortic diameter >0.5 cm/year. ^a, For TGFBR1 and TGFBR2, risk factors include systemic features (arterial tortuosity, hypertelorism, wide scars, small body surface area), rapid aortic expansion, and family history of aortic catastrophe (35). Aortic dissections at small diameters have been observed almost exclusively in women who have TGFBR2 mutations and a small body surface area and syndromic features (35). ^b, For BAV, risk factors include rapid aortic expansion and family history of aortic catastrophe (47). BAV, bicuspid aortic valve; FTAA, familial thoracic aortic aneurysm; HTAD, heritable thoracic aortic disease.