Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type.

Background: Ehlers-Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture, but the timing of th ese events, their frequency, and the course of the disease are not well doc umented. Methods: We reviewed the clinical and family histories of and medical and s urgical complications in 220 index patients with biochemically confirmed Eh lers-Danlos syndrome type IV and 199 of their affected relatives. We identi fied the underlying COL3A1 mutation in 135 index patients. Results: Complications were rare in childhood; 25 percent of the index pati ents had a first complication by the age of 20 years, and more than 80 perc ent had had at least one complication by the age of 40. The calculated medi an survival of the entire cohort was 48 years. Most deaths resulted from ar terial rupture. Bowel rupture, which often involved the sigmoid colon, acco unted for about a quarter of complications but rarely led to death. Complic ations of pregnancy led to death in 12 of the 81 women who became pregnant. The types of complications were not associated with specific mutations in COL3A1. Conclusions: Although most affected patients survive the first and second m ajor complications, Ehlers-Danlos syndrome type IV results in premature dea th. The diagnosis should be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or viscer al rupture. (N Engl J Med 2000;342:673-80.) (C)2000, Massachusetts Medical Society.