Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV)

Purpose: We sought to characterize the natural history of vascular Ehlers Danlos syndrome in individuals with heterozygous COL3A1 mutations. Methods: We reviewed clinical records for details of vascular, bowel, and organ complications in 1,231 individuals (630 index cases and 601 relatives). Results: Missense and splice-site mutations accounted for more than 90% of the 572 alterations that we had identified in COL3A1. Median survival was 51 years but was influenced by gender (lower in men) and by the type of mutation. Conclusion: Although vascular Ehlers Danlos syndrome appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1. These findings indicate that when counseling families, confirmation of the presence of a COL3A1 mutation and its nature can help evaluate the risks of complications. These data are also important ingredients in both the selection and allocation of individuals to appropriate arms in clinical trials to assess the effects of interventions.