Background: Ehlers-Danlos syndrome type IV, the vascular type, resultsfrom mutations in the gene for type III procollagen (COL3A1). Affectedpatients are at risk for arterial, bowel, and uterine rupture, but thetiming of these events, their frequency, and the course of the diseaseare not well documented.Methods: We reviewed the clinical and family histories of and medicaland surgical complications in 220 index patients with biochemicallyconfirmed Ehlers-Danlos syndrome type IV and 199 of their affectedrelatives. We identified the underlying COL3A1 mutation in 135 indexpatients.Results: Complications were rare in childhood; 25 percent of the indexpatients had a first complication by the age of 20 years, and more than80 percent had had at least one complication by the age of 40. Thecalculated median survival of the entire cohort was 48 years. Mostdeaths resulted from arterial rupture. Bowel rupture, which ofteninvolved the sigmoid colon, accounted for about a quarter ofcomplications but rarely led to death. Complications of pregnancy ledto death in 12 of the 81 women who became pregnant. The types ofcomplications were not associated with specific mutations in COL3A1.Conclusions: Although most affected patients survive the first andsecond major complications, Ehlers-Danlos syndrome type IV results inpremature death. The diagnosis should be considered in young people whocome to medical attention because of uterine rupture during pregnancyor arterial or visceral rupture. (N Engl J Med 2000;342:673-80.)(C)2000, Massachusetts Medical Society.