(798) Severe maternal Ehlers-Danlos diagnoses among patients referred for hypermobility

Friday, January 31, 2025

10:30 AM – 12:30 PM

Submitting Author and Presenting Author(s)

Kate Swanson, MD (she/her/hers)

Assistant Professor
University of California, San Francisco
San Francisco, California, United States

Coauthor(s)

Mary E. Norton, MD (she/her/hers)

Professor of Obstetrics, Gynecology & Reproductive Sciences
Center for Maternal-Fetal Precision Medicine, University of California San Francisco
San Francisco, California, United States
Teresa N. Sparks, MD, MS (she/her/hers)

Associate Professor, Maternal-Fetal Medicine and Clinical Genetics
Center for Maternal-Fetal Precision Medicine, University of California San Francisco
San Francisco, California, United States

Objective: Joint hypermobility may indicate multiple conditions, including hypermobile, vascular, and classic Ehlers Danlos syndromes (hEDS, vEDS, cEDS). While hEDS is associated with generally low risks and good pregnancy outcomes, vEDS carries a 5% risk of maternal mortality and cEDS an increased risk of spontaneous preterm birth. Our objective was to describe the prevalence of vEDS and cEDS in a cohort of preconception and pregnant individuals with hypermobility.

Study Design: Retrospective cohort study of individuals presenting for maternal genetic evaluation for hypermobility between 2023-2024. Individuals were offered gene panel testing that includes the genes associated with vEDS and cEDS (COL3A1, COL5A1, COL5A2). A diagnosis of hEDS or hypermobility spectrum disorder (HSD) was made clinically as the genes associated with this condition are poorly understood. Primary outcome was genetic diagnosis of vEDS or cEDS. Secondary outcomes were clinical features with each of these diagnoses.

Results: 26 individuals were evaluated for hypermobility. Genetic testing was pursued in 19 patients; an additional 2 patients had already undergone testing with nondiagnostic results and a clinical history consistent with hEDS. Among those tested, 2/19 (11%) were identified to have pathogenic or likely pathogenic variants in COL3A1 consistent with a diagnosis of vEDS, and were managed with cardiac surveillance and cesarean section. One of these two individuals had previously been diagnosed with hEDS by a primary care physician. No individuals were clearly identified with cEDS, though one patient had a variant of uncertain significance in COL5A2. The remaining individuals were clinically diagnosed with hEDS or HSD and had routine obstetric management (Figure). The Table shows clinical features across diagnoses.

Conclusion: vEDS was diagnosed in 11% of individuals tested after referral for hypermobility. Genetic evaluation should be considered in individuals with hypermobility due to overlapping features across disorders, as well as significant implications for clinical management of when vEDS or cEDS are identified.