Haploinsufficient FBN1 variants are associated with a higher risk of aortic complications in pregnant women with Marfan syndrome

Abstract

Background and purpose: Haploinsufficient (HI) FBN1 variants have been shown to be associated with a higher risk of aortic events in the Marfan syndrome (MFS) population compared with dominant negative (DN) variants. We sought to determine whether FBN1 genotype is associated with the rate of obstetric/fetal outcomes and aortic complications in prima- and multigravida women.

Methods: This retrospective study analyzed clinical data collected for 52 prima- and multigravidas with MFS who were genotype-positive for DN or HI FBN1 variants.

Results: Overall, 62% of the women developed primary (aortic dissection or aneurysm rupture) or secondary (corrective surgery or aortic dilatation) outcomes. The HI genotype was associated with a 4-fold higher rate of aortic events compared with the DN genotype (P = 0.03). The peripartum period tended to show a higher rate of aortic events in the HI group (0 DN vs 4 HI subjects, P = 0.14), in which 2 cases were fatal. MFS diagnosis was made after pregnancy in 60% of the subjects. There was no difference in obstetric/fetal outcomes between the DN and HI groups.

Conclusions: Pregnant women with HI variants in FBN1 had an overall higher rate of aortic events compared with those with DN variants. Our data suggest that women with suspected MFS may benefit from confirmatory molecular genetic testing prior to pregnancy.

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