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. Stanford 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.