Postpartum Presentation of a Variant of Uncertain Significance in COL3A1: A Case Report.

OBJECTIVE

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder associated with significant maternal morbidity and mortality during pregnancy. Conflicting recommendations exist for management, particularly in patients with variant of uncertain significance (VUS).

STUDY

DESIGN

We present a 39-year-old G2P1011 with a strong family history suggestive of vEDS who experienced an uncomplicated vaginal delivery followed by a large retroperitoneal hematoma requiring interventional radiology embolization and intensive care management for a postprocedural femoral pseudoaneurysm.

RESULTS

Postpartum genetic testing revealed a heterozygous VUS in COL3A1 (c.1297G>A [p.Glu433Lys]).

CONCLUSION

This case illustrates the challenges of counseling and managing pregnancy in patients with suspected vEDS and VUS, highlighting the importance of risk mitigation strategies, multidisciplinary care, and nuanced interpretation of genetic results.

KEY POINTS: · Risk stratification imaging: Whole-body vascular imaging beyond echocardiography may identify silent arterial lesions.. · Variant reclassification: Reporting pregnancy phenotypes linked to VUS in databases (ClinVar, LOVD) can accelerate variant reclassification and improve counseling.. · Structured counseling for uncertainty: Use a systematic approach when counseling patients with both a suspicious phenotype and a VUS, incorporating multidisciplinary perspectives and clearly communicating knowns and unknowns..