The vascular form of Ehlers-Danlos syndrome (type IV) is a result of mutations in the type III procollagen gene (COL3A1). Those affected are at risk for rupture of arteries, the bowel, and the uterus. This review looked at the clinical histories of 220 index patients with type IV Ehlers-Danlos syndrome, biochemically confirmed in all cases, and their medical and surgical complications. The COL3A1 mutation was identified in 135 patients. A comparison group consisted of 199 affected relatives. Twenty-six index patients and 105 relatives died, most often from arterial dissection or rupture. Thoracic and abdominal vessels were predominantly affected. More than two-thirds of all subjects had a single complication, and 21 percent had more than one complication. The chance of an index patient having a medical or surgical problem by age 20 was 25 percent and by age 40, more than 80 percent. Most bowel complications involved the colon, often its sigmoid portion.
Eighty-one women had experienced 183 pregnancies, 167 of which ended in term delivery of a liveborn infant. There were 3 stillbirths and 13 abortions (3 of them voluntary). Twelve women died during the peripartum period or within 2 weeks after delivery. Five deaths resulted from rupture of the uterus during labor. Vessel rupture caused seven deaths, two at delivery and five in the postpartum period. Five of 81 women who had been pregnant once died. Both club-foot deformity and congenital hip dislocation were more frequent than expected. The rate of premature birth in the index group was 12.4 percent, compared with 11 percent among the US population. In addition to a 50 percent chance of having an affected child, women with type IV Ehlers-Danlos syndrome are at a much increased risk of pregnancy complications. For this reason they should be followed at specialized centers. Rupture of the uterus at term is a prominent cause of death, but it is not clear whether elective cesarean delivery would limit mortality.
N Engl J Med 2000;342:673–680