Vascular Web Logo

SVS  SVS Foundation

 SS9 COL3A1 Gene Mutation Predicts Arterial Involvement and Prognosis in Vascular Ehlers Danlos Syndrome

Sherene Shalhub1, Nazli McDonnel2, Alana C. Cecchi1, Ali Azizzadeh1, Kristofer M. Charlton-Ouw1, James Black3, Reed Pyeritz4, Anthony L. Estrera1, Hazim Safi1, Dianna Milewicz1
1Department of Cardiothoracic & Vascular Surgery, The University of Texas Medical School at Houston, Houston, TX; 2National Institute on Aging, National Institute of Health, Baltimore, MD; 3Johns Hopkins Hospital, Baltimore, MD; 4University of Pennsylvania School of Medicine, Philadelphia, PA.

OBJECTIVES: Patients with vascular Ehlers-Danlos syndrome (vEDS) often present with spontaneous arterial dissection or rupture. Mutations in the COL3A1 gene that encodes type III collagen include missense mutations (MIS) and haploinsufficiency (HI) mutations. The aim is to describe the outcomes of vEDS patients based on genotype.
METHODS: Patients with confirmed molecular diagnosis of vEDS presenting at 2 tertiary referral centers from 2000-2012 were reviewed. Data collected included demographics, family history, vascular pathology, operative details and outcomes. To replicate the phenotype-genotype correlation a second cohort was reviewed using data from the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Registry (GenTAC), a National Institutes of Health-funded multicenter database.
RESULTS: A total of 62 cases (34% male, 75% with positive family history, 15% HI) were identified. Arterial aneurysms and dissections were seen in 38 (62%) cases. Median age at initial vascular presentation was 41 (range 39-58) years in the HI group vs. 33 (range 17-68) years in MIS group. Aortic and mesenteric arterial involvement was more common in the HI than MIS group (44% vs. 15% and 44% vs. 23%, respectively). The mortality was 0% in the HI group and 17% in the MIS group. The GenTAC registry enrolled 103 cases (29% male, 55% with positive family history, 6% HI). Median age at diagnosis was 28 (range 1-63) years. Once again, aortic involvement was more common in the HI vs. MIS group (50% vs. 10%).
CONCLUSIONS: Aortic and mesenteric arterial involvement in vEDS appears to be related to the underlying mutation type, with the HI cases having milder disease and later presentation. Molecular diagnosis is warranted in vEDS cases as it predicts postoperative outcomes and guides surveillance.
AUTHOR DISCLOSURES: A. Azizzadeh: Nothing to disclose; J. Black: Nothing to disclose; A. C. Cecchi: Nothing to disclose; K. M. Charlton-Ouw: Nothing to disclose; A. L. Estrera: Nothing to disclose; N. McDonnel: Nothing to disclose; D. Milewicz: Nothing to disclose; R. Pyeritz: Nothing to disclose; H. Safi: Nothing to disclose; S. Shalhub: Nothing to disclose.
Posted April 2013

Contact Us

Society for Vascular Surgery
633 North Saint Clair Street, 22nd Floor | Chicago, IL 60611
Phone: 312-334-2300 | 800-258-7188
Fax: 312-334-2320

Follow Us


VascularWeb® is the prime source for all vascular health and disease information, and is presented by the Society for Vascular Surgery®. Its members are vascular surgeons, specialists, and vascular health professionals who are specialty-trained in all treatments for vascular disease including medical management, non-invasive procedures, and surgery.