|Year : 2016 | Volume
| Issue : 1 | Page : 64-66
Embryological analysis of a case of exstrophy of the cloaca
Chongtham Rajlakshmi, Tanusri Debbarma
Department of Anatomy, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India
|Date of Web Publication||5-Feb-2016|
Department of Anatomy, Regional Institute of Medical Sciences (RIMS), Imphal - 795 001, Manipur
Source of Support: None, Conflict of Interest: None
A case is reported here of a stillborn fetus of about 21 weeks of gestation that was collected from the Department of Obstetrics and Gynecology, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India. The weight of the fetus was around 350 g. Crown rump (CR) length was not taken because of spine deformity and, therefore, the foot length, which measured 3.3 cm, was used to determine the age of the fetus. External examination of the fetus revealed an enormous defect in the anterior abdomen wall (omphalocele). The umbilical cord was attached on the right side of omphalocele. Incision of the membranous sac revealed liver, coils of intestine, and a muscular sac herniating through the defect in the abdominal wall. Further exploration of the abdomen showed continuity of the large intestine and ureters to the muscular sac. The sac is the cloaca. Exstrophy of the cloaca is a rare developmental anomaly involving the urinary bladder and the distal part of the digestive tract. This case report discusses the embryological background of the development of exstrophy of the cloaca and is reported because of the association of complete absence of external genitalia.
Keywords: Cloaca, exstrophy, omphalocele, single umbilical artery
|How to cite this article:|
Rajlakshmi C, Debbarma T. Embryological analysis of a case of exstrophy of the cloaca. J Med Soc 2016;30:64-6
| Introduction|| |
A case is reported here of a stillborn fetus of about 21 weeks of gestation that was collected from the Department of Obstetrics and Gynecology, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India. The present fetus was one of the fetuses collected for postgraduate thesis work for which formal permission from the Ethical Committee was obtained for research purposes. The weight of the fetus was around 350 g. Crown rump (CR) length was not taken because of spinal deformity and, therefore, foot length was used to determine the age of the fetus. The foot length was 3.3 cm. External examination of the fetus revealed an enormous defect in anterior abdominal wall (omphalocele). Defect was covered by an intact membranous sac, composed of amnion externally and parietal peritoneum internally [Figure 1]. The umbilical cord was attached on the right side of omphalocele. Incision of the membranous sac revealed herniated liver, coils of intestine, and ventral wall deficit muscular sac through the defect in the abdominal wall. Further, exploration of the abdomen showed continuity of the large intestine of the muscular sac [Figure 2]. Ureters too, opened into the muscular sac [Figure 3]. The muscular sac had no opening in the lesser pelvis. This sac is the cloaca that is devoid of anterior wall and herniated through the ventral body wall defect. The genital and perineal areas were smooth with no sign of external genitalia or anal opening. Scoliosis with convexity to the left was present. Consequently, the left lung was hypoplastic. The right lung and the heart were normal. Dorsal aorta continued as a single right umbilical artery. Hence, the umbilical cord had a right umbilical artery and an umbilical vein. The umbilical cord was inserted on the right side of the membranous sac. Umbilical vein continued into the falciform ligament. Both the portal vein and inferior vena cava were absent. Malrotation of the lower limb was observed. Both the lower limbs were rotated laterally by 90°, resulting in malorientation of the surfaces and borders, thereby the ventral aspect of both the lower limbs faced dorsally, tibial bones were situated on the lateral aspect and the fibular bones, the vice versa. The little toes of both the feet were situated in the midsagittal plane. Second toe of the left foot overrode the first toe.
|Figure 2: Terminal portion of the hindgut (upper arrow) opening into the posterior cloaca (lower arrow)|
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|Figure 3: Photograph showing ureteric opening (arrow) in the cloacal chamber|
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| Discussion|| |
Exstrophy of the cloaca is a severe defect in the development of the urinary bladder and caudal part of the gastrointestinal tract that are exposed through a severe ventral body wall defect. A reported incidence of 1 of 200,000 to 1 of 400,000 makes it one of the rarer urologic abnormalities as compared to exstrophy of bladder that is reported to be 1 in 40,000 births. All these malformations are about twice as common in males as in females.  Developmentally, cloaca (Latin for sewer) is the expanded caudal end of primitive hindgut that receives the allantoic diverticulum and later, the mesonephric ducts. It is separated from the exterior by the cloacal membrane. Cloaca is differentiated into the urogenital sinus anteriorly and the primitive anal canal posteriorly that occurs around the 4 th -7 th week of embryonic life when the embryo is of 5 mm CR length. The urogenital sinus further differentiates into urinary bladder and urethra, and the primitive anal canal develops into the proximal part of the anal canal. This differentiation of cloaca into two chambers takes place by the migration of mesodermal cells called urorectal septum in the coronal plane. The origin of the mesoderm cells are from the primitive streak and as well from the mesoderm covering the yolk sac and the surrounding allantois.  The urorectal septum is formed by two probably combined methods:
- A more or less coronal fold (of Tourneux) growing caudally and
- Two lateral folds (of Rathke) that fuse in the median plane, further caudally. 
The urogenital septum eventually grows caudally toward the cloacal membrane and fuses with it when the embryo is around 16 mm CR length. The area of fusion is the perineal body. At this stage, the cloacal membrane in front of the perineal body is called the urogenital membrane and the part behind it is called the anal membrane. This is followed by the rupture of the cloacal membrane around the 7 th week. Failure in the migration of mesoderm leads to rupture of the cloacal membrane that extends cranially, creating exstrophy of the cloaca.  In the present case, the perineal area is absolutely smooth without external genitalia, no anal opening, and no natal cleft. When this migration does not take place, rupture of the cloacal membrane extends cranially, creating exstrophy of the cloaca. External genitalia start developing around the 3 rd week by the migrating mesenchymal cells, originating in the primitive streak. In the present case it is speculated that insult to the developing embryo had taken place between the 3 rd and the 7 th week. 
The abdominal wall defect in these conditions may be a secondary effect of anomalous development of the cloacal membrane and two causative theories have been reported. First, when the cloacal membrane is abnormally large, it breaks down to produce an opening too wide to permit normal midline fusion of the tissue layers on either side of it. Consequently, migration of mesoderm to the midline is inhibited and the tail fold fails to progress, and thus gives rise to a severe ventral body wall defect.  The second theory posits an inability to reduce the size of the cloacal membrane at its superior and lateral sides because of insufficient tissue proliferation and migration in the infraumbilical region. Coupled with the membrane's subsequent rupture, this could additionally lead to exstrophy of the cloaca, epispadias, or exstrophy of the urinary bladder, depending on the degree and timing of the deficiencies. 
Local ectodermal/mesenchymal interactions give rise to anal sphincter that will develop without the presence of urorectal septum or anal canal.  However, we observed the absence of anal sphincter in the present case, prompting us to postulate that mesodermal tissue from the urorectal septum could be a tissue necessary for the development of the anal sphincter. The underlying genetic and molecular mechanisms responsible in the partitioning of the cloaca are not clearly understood. Study in zebrafish had shown that sustained bone morphogenetic protein (Bmp) signaling from the mid-gastrula stage through somitogenesis is important for excluding blood and vascular precursors from the extreme ventral mesoderm and this domain is normally required for the development of the cloaca. HrT, a T-box transcription factor, a Bmp-regulated gene has an essential function in cloacal development. Alteration in Bmp signaling is the cause of cloacal maldevelopment.  In a mouse model and chick embryo, partitioning of the cloaca into ventral urinary and dorsal alimentary tracts requires GLI family zinc finger 2 (Gli2), a zinc finger transcription factor of sonic hedgehog (Shh) protein in the patterning and differentiation of the cloaca. 
Many of the symptom complexes that affect the caudal region, have overlapping symptoms to the extent of difficulties in delineating the syndromes. Mention may be made of omphalocele, exstrophy of bladder, imperforate anus, spinal defect with or without meningomyelocele (OEIS complex), limb-body wall defect (body wall defect, evisceration of viscera, limb defect, craniofacial defect), and prune-belly syndrome (defective abdominal wall, urinary anomalies, and cryptorchidism). In the OEIS complex, single umbilical artery is reported to be present.  However, the complete absence of genitalia in the OEIS complex is, to our knowledge, not yet reported. And, specific vertebral defect in the present case is scoliosis. Thus, this case report is a rare association of the OEIS complex with the nondevelopment of external genitalia.
| Conclusion|| |
The present case is reported for multiple congenital abnormalities with a prominent feature of the absence of external genitalia along with exstrophy of the cloaca. It is speculated that such an abnormality could be the result of failure in the migration of mesoderm and rupture of cloacal membrane during the 3 rd week to the 7 th week of embryonic life giving rise to exstrophy of the cloaca. Hence, the crucial period of development of external genitalia and cloaca is between 3 rd and 7 th week.
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[Figure 1], [Figure 2], [Figure 3]