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
(Not long ago, I attended a patient in labor who was referred with a diagnosis of Ehlers-Danlos syndrome (EDS). Her obstetric history indicated a previous traumatic vaginal delivery with disruption of the lower vagina, anal sphincter, and rectum; 2 years after that event, she was in labor again. The first child did not have EDS. The reason for transfer was that a larger medical center would be better able to handle the potential for traumatic delivery and hemorrhage. Fortunately, the woman's labor was rapid, and she delivered a smaller baby, compared with her first child, with only minor extension of a medial lateral episiotomy. Unfortunately, this child did have EDS type IV.
Type IV EDS is an autosomal dominant disorder that results from a mutation in the gene for type III procollagen; the diagnosis is usually made after major rupture of arteries of the intestine or the uterus during pregnancy. Pepin et al. reviewed the clinical and family histories of 220 index patients with biochemically confirmed EDS type IV and 199 of their affected relatives. Complications were rare in childhood; 25 percent of the index patients had their first complication by the age of 20; more than 80 percent had at least one complication by the age of 40. The 81 women had 183 pregnancies with 167 deliveries of liveborn infants at term, 3 stillbirths, 10 spontaneous abortions, and 3 voluntary terminations. Twelve of the 81 women died in the peripartum period or within 2 weeks after delivery (5 of uterine rupture during labor, 2 of vessel rupture at delivery, and 5 in the postpartum period after vessel rupture). The authors do not recommend the use of elective cesarean delivery at term even though several pregnant women died of uterine rupture at term (N Engl J Med 2000;342:673).
The signs and symptoms of EDS range from minimum findings of translucent skin, easy bruising and skin scarring, skin and joint laxity, and hypermobility in type I EDS to fatal arterial rupture in type IV vascular EDS. Obstetric complications include preterm or premature rupture of the membranes, rupture of major arterial blood vessels, and tearing of the uterus, perineum, vagina, urethra, and bladder during vaginal delivery. There are different EDS subtypes; types I through III are the most common forms, whereas EDS type IV is one of the rarest and most severe subtypes. In 1981, D. J. Taylor et al. wrote a review for the Survey about the EDS during pregnancy. The authors indicated that most of the literature on the syndrome is anecdotal. There is an estimated population incidence of 1:150,000 to 1:200,000. The authors believe that the severe forms of the syndrome were associated with risk of hemorrhage, severe trauma at delivery, and preterm labor. Review of the literature did not suggest that delivery by cesarean was indicated in all cases of EDS (Survey 1981;36:277). In 1982, Smith and Phelan reported two cases of EDS complicating pregnancies. One patient had EDS type II and had a vaginal delivery of a normal infant at term. The second patient, who also had EDS type II, had a vaginal delivery at term with severe disruption of the vagina and perineum. Surgical complications relate to the inability to suture skin and an increased rate of wound separation. The fetal complications relate to a friable umbilical cord, congenital hip dislocation, and poor muscle tone at birth (J Reprod Med 1982;27:757). Obstetricians should be alert to the possible presence of EDS when confronted with a patient with a personal or family history of increased bruisability, recurrent bleeding with normal clotting test, severe varicosities, strong family history of recurrent pelvic floor relaxation, uterine prolapse, and repeated wound dehiscence after surgical procedures; a skin biopsy should be taken for histologic and biochemical analyses. The management of patients with EDS in pregnancy consists of early attempts at clinical classification and genetic counseling. Cesarean delivery should be reserved for obstetric indications solely; vaginal delivery may be associated with vaginal lacerations and hematoma formation. Transferring patients to a larger medical center might be prudent so that all possible eventualities might be expeditiously handled; however, some disasters might not be avoidable.-RCC)