Inherited thrombophilia: a possible cause of in utero vascular thrombosis in children with intestinal atresia

Background: Congenital atresia of the small and large intestine is thought to evolve from in utero mesenteric vascular occlusion of the corresponding intestinal segment. Because spontaneous thrombosis recently has been descri bed in association with inherited thrombophilia, the authors wondered if in herited thrombophilia also might be found in babies with intestinal atresia . Methods: Genetic analysis was done on 28 children treated for congenital in testinal atresia. DNA was analyzed for point mutations to detect the 2 most common types of inherited thrombophilia, the G1691A mutation in the factor V gene (factor V Leiden) and the G20210A mutation in the prothrombin gene. In addition, other genetic risk factors for thrombosis were analyzed inclu ding the C677T mutation in the methylenetetrahydrofolate reductase gene (MT HFR) and 2 polymorphisms of the factor VII gene (the R353Q and the hypervar iable region 4 polymorphisms). Results: The factor V Leiden mutation was present in 5 of 28 (18%) children treated for congenital intestinal atresia. This is increased significantly when compared with the reported carrier frequency of 3% to 7% in the gener al population and a reported carrier rate of 4.2% in the local population ( P <.005). The R353Q polymorphism of the factor VII gene, specifically the R R genotype, was noted in 85% of patients with atresia with an expected freq uency of 64% (P <.008). There were no significant associations noted betwee n mutations in the prothrombin gene, the MTHFR gene, or the hypervariable r egion of the factor VII gene. Conclusions: The factor V Leiden mutation and the RR subtype of the R353Q p olymorphism of the factor VII gene are seen at an increased frequency in ch ildren with congenital intestinal atresia. This suggests that inherited thr ombophilia may play a role in the etiology of these in utero mesenteric thr ombotic events. J Pediatr Surg 36:1146-1149. Copyright (C) 2001 by W.B. Sau nders Company.