A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis

Sherene Shalhub, Peter H. Byers, Kelli L. Hicks, Dawn M. Coleman, Frank M. Davis, Giovanni De Caridi, K. Nicole Weaver, Erin M. Miller, Marc L. Schermerhorn, Katie Shean, Gustavo Oderich, Mauricio Ribeiro, Cole Nishikawa, Kristofer Charlton-Ouw, Christian Alexander Behrendt, E. Sebastian Debus, Yskert von Kodolitsch, Devin Zarkowsky, Richard J. Powell, Melanie PepinDianna M. Milewicz, Ellen S. Regalado, Peter F. Lawrence, Karen Woo

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. Methods: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. Results: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P <.001), mitral valve prolapse (10.5% vs 1.2%; P =.009), and joint hypermobility (68.4% vs 40.7%; P <.001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P <.001), thin translucent skin (17.1% vs 48.8%; P <.001), intestinal perforation (3.9% vs 16.3%; P =.01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P =.13). There were no differences in mortality or age of mortality between the two cohorts. Conclusions: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalJournal of vascular surgery
Volume71
Issue number1
DOIs
StatePublished - Jan 2020

Keywords

  • COL3A1 mutation
  • Heritable arteriopathies
  • Vascular Ehlers-Danlos syndrome
  • Vascular genetic testing

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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    Shalhub, S., Byers, P. H., Hicks, K. L., Coleman, D. M., Davis, F. M., De Caridi, G., Weaver, K. N., Miller, E. M., Schermerhorn, M. L., Shean, K., Oderich, G., Ribeiro, M., Nishikawa, C., Charlton-Ouw, K., Behrendt, C. A., Debus, E. S., von Kodolitsch, Y., Zarkowsky, D., Powell, R. J., ... Woo, K. (2020). A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis. Journal of vascular surgery, 71(1), 149-157. https://doi.org/10.1016/j.jvs.2019.04.487