Association of Cloacal Anomalies, Caudal Duplication, and Twinning JOSEPH R. SIEBERT , 1,2 *JOE C. RUTLEDGE, 1,3 AND RAJ P. KAPUR 1,2 1 Department of Laboratories (A-6901), ChildrenÕs Hospital and Regional Medical Center, Post Office Box 5371, Seattle, WA 98105, USA 2 Department of Pathology, Box 357470, University of Washington, Seattle, WA, USA 3 Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA Received January 26, 2005; accepted February 7, 2005; published online July 14, 2005. ABSTRACT Cloacal anomalies exhibit a wide variety of morpho- logic types and accompanying clinical severity. The association of malformations of the cloaca with par- tial, complete, or conjoined twinning has been appre- ciated for some time, but, with the advent of prenatal ultrasound technology, appears to occur with a greater frequency than once thought. This observation has important implications for pathogenesis. We present 2 representative cases, a 19-week-old female fetus with duplication of several caudal structures and a 21- week-old male fetus with cloacal exstrophy variant and demised co-twin with lower abdominal wall de- fect, extruded intestinal tract, absent external genita- lia, and imperforate anus. These findings and previously published theories suggest that certain models of monozygotic twinning may apply to the pathogenesis of cloacal anomalies. Specifically, the partial or complete duplication of the organizing center within a single embryonic disc may increase the risk of mesodermal insufficiency and thus account for the failure of complete development of the cloacal membrane and consequent exstrophy or other aber- ration. Key words: cloaca, conjoined twin, exstrophy, para- sitic twin, partial twin, twin INTRODUCTION The pathogenesis of cloacal anomalies and asso- ciated malformations is complex and in need of further clarification. Major contributions to the understanding of cloacal embryology were made by Marshall and Muecke in the 1960s [1,2]. Beckwith was soon to appreciate these insights and integrate them into his own views on the development of the abdominal wall [3]. This was a region of obvious interest, as evidenced by a later contribution [4]. The wide phenotypic and clinical variability of cloacal defects is shown in Fig. 1. In the 1980s, several case reports describing the association of cloacal anomalies and twinning appeared [5–7]. This association, although poten- tially informative, is poorly understood. In the past, it was manifest chiefly by twins presenting at or near term, and the prevalence of younger twins with cloacal anomalies could only be approxi- mated. These estimates did not take into account the early, unrecognized loss of co-twins. Advances in technology, most notably prenatal ultrasound, have enabled workers to recognize twin gestations and cloacal malformations much earlier in gesta- tion [8–11]. It is clear from these observations that multiple gestations occur more often than is evi- dent at mid-gestation or later, and that twinning is *Corresponding author, e-mail: joseph.siebert@seattlechildrens.org Pediatric and Developmental Pathology 8, 339–354, 2005 DOI: 10.1007/s10024-005-1157-6 ª 2005 Society for Pediatric Pathology