Impact of Pathogenic Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome.

Background: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between genotype and severe aortopathy (aortic root replacement, type A dissections, and related death).

Methods: We evaluated 248 patients with pathogenic or likely pathogenic variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the genotype on severe aortic events (aortic root replacement, type A dissections, and related death).

Results: The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; <0.001).

Conclusions: DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.