The impact of FBN1 variant types on pregnancy-related aortic dissection in women with Marfan syndrome

BACKGROUND: Pregnancy in women with Marfan syndrome (MFS) increases the risk of aortic dissection, yet management based solely on aortic root diameter often fails to predict this complication, particularly Stanford type B dissection. Haploinsufficient (HI) FBN1 variants are associated with more severe aortic phenotypes. We investigated the relationship between FBN1 genotype and pregnancy-related aortic dissection in women with MFS. METHODS: We retrospectively analyzed women with genetically confirmed MFS whose pregnancies progressed beyond the second trimester and who were managed at a single tertiary referral center between 1993 and 2024. FBN1 variants were categorized as HI or non-HI. Pregnancy-related aortic dissection-defined as occurring during pregnancy or within six months postpartum-was evaluated in relation to variant type. RESULTS: Thirty-five women (15 HI, 20 non-HI) were included. Pregnancy-related aortic dissection occurred in 11 women: seven were referred after the dissection occurred and nine were Stanford type B. The incidence was higher in the HI group than in the non-HI group (9/15 60% vs 2/20 10%, P = 0.002). Pre-pregnancy native aortic root diameters did not differ between those with and without dissection. Additional risk factors included undiagnosed with MFS at the time of dissection and absence of β-blocker therapy. CONCLUSIONS: HI FBN1 variants were associated with pregnancy-related aortic dissection in this cohort. Type B dissection may occur even with mild aortic dilation, highlighting the limitations of diameter-based risk stratification. Incorporating FBN1 genotype into preconception counseling and pregnancy management may improve maternal outcomes. However, given the retrospective single-center design, prospective validation is warranted.