Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe autosomal dominant disorder caused by variants at the COL3A1 gene. Clinical characteristics and course of disease of 215 molecularly proven patients (146 index cases and 69 relatives) were analysed. We found 126 distincts variants that were divided into five groups: (1) Glycine substitutions (n = 71), (2) splice-site and in-frame insertions-deletions (n = 36), (3) variants leading to haplo-insufficiency (n = 7), (4) non-glycine missense variants within the triple helix (n = 4 variants), and (5) non-glycine missense variants or in-frame insertions-deletions, in the N-or C-terminal part of the protein (n = 8). Overall, our cohort confirmed the severity of the disease with a median age at first complication of 29 years (IQR 22-39), the most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1 were significantly more severe than groups 3-5, with extreme median ages at first major complication of 23-47 years. Patients of groups 3-5 had a less typical phenotype and remarkably absence of digestive events. The distribution of glycine-replacing amino acids was strongly biased towards more destabilizing residues of the collagen assembly. Thus the natural course of vEDS and the clinical phenotype of patients are influenced by the type of COL3A1 variant. This study also confirms that patients with variants located in the C-and N-termini or leading to haplo-insufficiency have milder course of the disease and less prevalent diagnostic criteria. These findings may help refine diagnostic strategy, genetic counselling and clinical care.

AimEvaluation of the aortic “elastic reserve” might be a relevant marker to assess the risk of aortic event. Our aim was to compare regional aortic elasticity at rest and during supine bicycle exercise at 1.5 T MRI in healthy individuals.MethodsFifteen volunteers (8 men), with a mean age of 29 (23–41) years, completed the entire protocol. Images were acquired immediately following maximal exercise. Retrospective cine sequences were acquired to assess compliance, distensibility, maximum rates of systolic distension and diastolic recoil at four different locations: ascending aorta, proximal descending aorta, distal descending aorta and aorta above the coeliac trunk level. Segmental aortic pulse wave velocity (PWV) was assessed by through plane velocity-encoded MRI.ResultsExercise induced a significant decrease of aortic compliance and distensibility, and a significant increase of the absolute values of maximum rates of systolic distension and diastolic recoil at all sites (p<10–3). At rest and during stress, ascending aortic compliance was statistically higher compared to the whole descending aorta (p≤0.0007). We found a strong correlation between the rate pressure product and aortic distensibility at all sites (r = - 0.6 to -0.75 according to the site, p<10–4). PWV measured at the proximal and distal descending aorta increased significantly during stress (p = 0.02 and p = 0.008, respectively).ConclusionAssessment of regional aortic function during exercise is feasible using MRI. During stress, aortic elasticity decreases significantly in correlation with an increase of the PWV. Further studies are required to create thresholds for ascending aorta dysfunction among patients with aneurysms, and to monitor the impact of medication on aortic remodeling.

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