A Multi-Institutional Experience in Vascular Ehlers-Danlos Syndrome

Objective: Vascular Ehlers-Danlos syndrome (VEDS) is a rare connective tissue disorder with >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 aimed to provide a description of a contemporary cohort of patients diagnosed with VEDS. Methods: This was a multi-institutional retrospective cohort study of patients diagnosed with VEDS between 2000 and 2015. Demographics, family history, diagnosis modality, COL3A1 mutations, vascular disease, and management data were collected. Data were presented as median and ranges. Patients with confirmed causative COL3A1 mutations were analyzed for vascular disease. Results: Eleven institutions identified 173 (35.3% male) patients with VEDS. Median age at diagnosis was 26.5 (range, 0.1-81) years by genetic testing, skin biopsy, and 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 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 noncausative. Among those with a causative mutation, 42 (62.9%) were diagnosed with arterial dissections 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 3 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 toward an accurate understanding of the disease and operative outcomes, thus facilitating clear guidelines for management