A Multi-institutional Experience in Vascular Ehlers Danlos Syndrome
Sherene Shalhub, MD MPH1, Kelli Hicks, BS1, Karen Woo, MD2, Dawn Coleman, MD3, Frank Davis, MD3, Giovanni De Caridi, MD PhD4, K. Nicole Weaver, MD5, Erin Miller, MS CGC6, Marc Schermerhorn, MD7, Katie Shean, MD7, Gustavo Oderich, MD8, Mauricio Ribiero, MD PhD8, Cole Nishikawa, MD9, Kristofer M. Charlton-Ouw, MD10, Christian-Alexander Behrendt, MD11, Sebastian Debus, MD PhD11, Yskert von Kodolitsch, MD12, Devin Zarkowsky, MD13, Richard J. Powell, MD13, Melanie Pepin, MS CGC14, Peter Byers, MD15, Peter Lawrence, MD2.
1University of Washington, Seattle, WA, USA, 2Division of Vascular Surgery, University of California Los Angeles, Los Angeles, CA, USA, 3Section of Vascular Surgery, University of Michigan, Ann Arbor, MI, USA, 4Department of Cardiovascular and Thoracic Sciences, University of Messina, Messina, Italy, 5Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cinncinnati, OH, USA, 6The Heart Institute and Division of Human Genetics at Cincinnati Children's, Cinncinnati, OH, USA, 7Beth Israel Deaconess Medical Center, Boston, MA, USA, 8Mayo Clinic Division of Vascular Surgery, Rochester, MN, USA, 9University of California, Davis Medical Center, Sacramento, CA, USA, 10Department of Cardiothoracic and Vascular Surgery, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA, 11Department of Vascular Medicine, University Heart Center Hamburg, Hamburg, Germany, 12Department of Cardiology, University Heart Center, Hamburg, Germany, 13Division of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, 14Medical Genetics, Department of Pathology, Seattle, WA, USA, 15Medical Genetics, Department of Pathology, University of Washington, Seattle, WA, USA.
OBJECTIVE. Vascular Ehlers-Danlos syndrome (VEDS) is a rare connective tissue disorder with over 700 mutations in the COL3A1 gene affecting collagen type III production. Limited data exist regarding the consequent aortic and branch vessel aneurysms and dissections presentation and treatment outcomes. This study aims to provide a description of a contemporary cohort of patients diagnosed with VEDS. METHODS. Multi-institutional retrospective cohort study of patients diagnosed with VEDS between 2000 and 2015. Demographics, family history, diagnosis modality, COL3A1 mutations, vascular pathology, and management data were collected. Data were presented as median and ranges. Patients with confirmed causative COL3A1 mutations were analyzed for vascular pathology. RESULTS. Eleven institutions identified 173 (35.3% male) patients with VEDS. Median age of diagnosis was 26.5 (range 0.1-81) years via genetic testing, skin biopsy, or clinical criteria in 63%, 3%, and 18% of the cases respectively. In 16.2% the diagnosis method was unknown. A family history of confirmed or suspected VEDS, sudden death, stroke, or myocardial infarction was documented in 47.4% of the cases. Arterial dissections and/or aneurysms were diagnosed in 81 cases (51.9% male). At the time of data collection 11.6% of the patients died at a median age of 37 (range 19-70) years, with 95% due to vascular complications. COL3A1 mutation data were available for 79 cases (46.9% male, 5 null mutations). In 15.2% of the cases, the COL3A1 mutations were found to be non-causative. Among those with a causative mutation, 42 (62.9%) were diagnosed with arterial dissections and/or aneurysms (50% male, 3 null mutations) at a median age of 31.5 (range 12-79) years. This involved the carotid/vertebral, mesenteric/renal, and iliac arteries in 35.7%, 47.6%, and 31% of the cases respectively. Aortic involvement occurred in 23.8% of the cases. Mortality in this group was 16.7% at a median age of 43 (range 22-70) years. Vascular interventions were undertaken in 15 (35.7%) cases (10 open, 5 endovascular). Of which three were for rupture (thoracic aorta, abdominal aorta, and splenic artery). CONCLUSIONS. This is a large, multi-institutional descriptive study of patients diagnosed with VEDS. The study highlights the importance of establishing a precise diagnosis by confirming a causative COL3A1 mutation. This is a first step towards an accurate understanding of the disease pathology and operative outcomes thus facilitating clear guidelines for management.
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