Pediatric and Developmental Pathology

, Volume 8, Issue 3, pp 339–354 | Cite as

Association of Cloacal Anomalies, Caudal Duplication, and Twinning

  • Joseph R. Siebert
  • Joe C. Rutledge
  • Raj P. Kapur
Article

Abstract

Cloacal anomalies exhibit a wide variety of morphologic types and accompanying clinical severity. The association of malformations of the cloaca with partial, complete, or conjoined twinning has been appreciated 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 defect, extruded intestinal tract, absent external genitalia, 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 aberration.

Keywords

cloaca conjoined twin exstrophy parasitic twin partial twin twin 

Notes

Acknowledgments

We are grateful for the expert consultation afforded us in case 2 by Michael E. Mitchell, MD.

References

  1. 1.
    Marshall VF, Muecke EC. Variations in exstrophy of the bladder. J Urol 1962;88:766–796Google Scholar
  2. 2.
    Muecke E. The role of the cloacal membrane in exstrophy—the first successful experimental study. J Urol 1964;92:659–667PubMedGoogle Scholar
  3. 3.
    Beckwith JB. The congenitally malformed VII. Exstrophy of the bladder and cloacal exstrophy. Northwest Med 1966;65:407–410PubMedGoogle Scholar
  4. 4.
    Beckwith JB. Macroglossia, omphalocele, adrenal cytomegaly, gigantism and hyperplastic visceromegaly. Birth Defects Orig Art Ser 1969;5:188–196Google Scholar
  5. 5.
    McLaughlin JF, Marks WM, Jones G. Prospective management of exstrophy of the cloaca and myelocystocele following prenatal ultrasound recognition of neural tube defects in identical twins. Am J Med Genet 1984;19:721–7CrossRefPubMedGoogle Scholar
  6. 6.
    Ornoy A, Navot D, Menashi M, Laufer N, Chemke J. Asymmetry and discordance for congenital anomalies in conjoined twins: a report of six cases. Teratology 1980;22:145–154CrossRefPubMedGoogle Scholar
  7. 7.
    Redman J, Seibert J, Page B. Cloacal exstrophy in identical twins. Urology 1981;17:73–74CrossRefPubMedGoogle Scholar
  8. 8.
    Austin PF, Homsy YL, Gearhart JP, Porter K, Guidi C, Madsen K, et al. The prenatal diagnosis of cloacal exstrophy. J Urol 1998;160:1179–1181CrossRefPubMedGoogle Scholar
  9. 9.
    Kutzner DK, Wilson WG, Hogge WA. OEIS complex (cloacal exstrophy): prenatal diagnosis in the second trimester. Prenat Diagn 1988;8:247–253PubMedGoogle Scholar
  10. 10.
    Landy HJ, Keith LG. The vanishing twin: a review. Hum Reprod Update 1998;4:177–183CrossRefPubMedGoogle Scholar
  11. 11.
    Meizner I, Levy A, Barnhard Y. Cloacal exstrophy sequence: an exceptional ultrasound diagnosis. Obstet Gynecol 1995;86:446–450CrossRefPubMedGoogle Scholar
  12. 12.
    Casale P, Grady RW, Waldhausen JH, Joyner BD, Wright J, Mitchell ME. Cloacal exstrophy variants. Can blighted conjoined twinning play a role? J Urol 2004;172:1103–1107CrossRefPubMedGoogle Scholar
  13. 13.
    Chitrit Y, Zorn B, Filidori M, Robert E, Chasseray JE. Cloacal exstrophy in monozygotic twins detected through antenatal ultrasound scanning. J Clin Ultrasound 1993;21:339–342PubMedGoogle Scholar
  14. 14.
    Lee DH, Cottrell JR, Sanders RC, Meyers CM, Wulfsberg EA, Sun C-CJ. OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects) in monozygotic twins. Am J Med Genet 1999;84:29–33CrossRefPubMedGoogle Scholar
  15. 15.
    Azmy AF. Complete duplication of the hindgut and lower urinary tract with diphallus. J Pediatr Surg 1990;25:647–649CrossRefPubMedGoogle Scholar
  16. 16.
    Dominguez R, Rott J, Castillo M, Pittaluga RR, Corriere JN Jr. Caudal duplication syndrome. Am J Dis Child 1993;147:1048–1052PubMedGoogle Scholar
  17. 17.
    Ravitch MM, Scott WW. Duplication of the entire colon, bladder, and urethra. Surgery 1953;34:843–858Google Scholar
  18. 18.
    Evans JA, Chudley AE. Tibial agenesis, femoral duplication, and caudal midline anomalies. Am J Med Genet 1999;85:13–19CrossRefPubMedGoogle Scholar
  19. 19.
    La Torre R, Fusaro P, Anceschi MM, Montanino-Oliva M, Modesto S, Cosmi EV. Unusual case of caudal duplication (dipygus). J Clin Ultrasound 1998;26:163–165CrossRefPubMedGoogle Scholar
  20. 20.
    Ulman I, Avanoglu A, Erdener A, Sahin AH, Gokdemir A. Evaluation of the lower urinary tract function in caudal duplication (dipygus) anomaly. J Pediatr Surg 1996;31:1680–1681CrossRefPubMedGoogle Scholar
  21. 21.
    Bannykh SI, Bannykh GI, Mannino FL, Jones KL, Hansen L, Benirschke K, et al. Partial caudal duplication in a newborn associated with meningomyelocele and complex heart anomaly. Teratology 2001;63:94–99CrossRefPubMedGoogle Scholar
  22. 22.
    Gastol P, Baka-Jakubiak M, Skobejko-Wlodarska L, Szymkiewicz C. Complete duplication of the bladder, urethra, vagina, and uterus in girls. Urology 2000;55:578–581CrossRefPubMedGoogle Scholar
  23. 23.
    Gyftopoulos K, Wolffenbuttel KP, Nijman RJM. Clinical and embryologic aspects of penile duplication and associated anomalies. Urology 2002;60:675–679CrossRefPubMedGoogle Scholar
  24. 24.
    Jimenez SG, Oliver MR, Stokes KB, Morreau PN, Chow CW. Case report: colonic duplication: a rare cause of obstruction. J Gastroenterol Hepatol 1999;14:889–892CrossRefPubMedGoogle Scholar
  25. 25.
    Salman AB. Cloacal duplication. J Pediatr Surg 1996;31:1587–1588CrossRefPubMedGoogle Scholar
  26. 26.
    Payne CE, Deshon GE Jr, Kroll JD, Sumfest J. Colonic duplication: an unusual cause of enterovesical fistula. Urology 1995;46:726–728CrossRefPubMedGoogle Scholar
  27. 27.
    Hunter TB, Tonkin IL. Complete duplication of the colon in assoication with urethral duplication. Gastrointest Radiol 1979;4:93–95CrossRefPubMedGoogle Scholar
  28. 28.
    Currie AB, Hemalatha VH, Doraiswamy NV. Duplications of the alimentary tract. J R Coll Surg Edinb 1978;23:347–354PubMedGoogle Scholar
  29. 29.
    Potter E. Pathology of the Fetus and Infant, 2nd ed. Chicago: Yearbook Medical Publishers, 1969Google Scholar
  30. 30.
    Soper R. Tubular duplication of the colon and distal ileum: case report and discussion. Surgery 1968;63:998–1000PubMedGoogle Scholar
  31. 31.
    Collins D. A study of 50,000 specimens of the human vermiform appendix. Surg Gynecol Obstet 1955;101:437–445PubMedGoogle Scholar
  32. 32.
    Nielsen OH, Nielsen R, Parvinen T. Duplicate exstrophy of the bladder. Ann Chir Gynaecol 1980;69:32–36PubMedGoogle Scholar
  33. 33.
    Muller F, O’Rahilly R. The primitive streak, the caudal eminence and related structures in staged human embryos. Cells Tissues Organs 2004;177:2–20CrossRefPubMedGoogle Scholar
  34. 34.
    Griffith CM, Wiley MJ, Sanders EJ. The vertebrate tail bud: three germ layers from one tissue. Anat Embryol 1992;185:101–113CrossRefPubMedGoogle Scholar
  35. 35.
    Keppler-Noreuil KM. OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): a review of 14 cases. Am J Med Genet 2001;99:271–279CrossRefPubMedGoogle Scholar
  36. 36.
    Pourquie O. The chick embryo: a leading model in somatogenesis studies. Mech Dev 2004;121:1069–1079CrossRefPubMedGoogle Scholar
  37. 37.
    Alles AJ, Sulik KK. A review of caudal dysgenesis and its pathogenesis as illustrated in an animal model. Birth Defects Orig Art Ser 1993;29:83–102Google Scholar
  38. 38.
    Rutledge JC, Shourbaji AG, Hughes LA, Polifka JE, Cruz YP, Bishop JB, et al. Limb and lower-body duplications induced by retinoic acid in mice. Proc Natl Acad Sci USA 1994;91:5436–5440PubMedGoogle Scholar
  39. 39.
    Kroes HY, Takahashi M, Zijlstra RJ, Baert JA, Kooi KA, Hofstra RM, et al. Two cases of the caudal duplication anomaly including a discordant monozygotic twin. Am J Med Genet 2002;112:390–393CrossRefPubMedGoogle Scholar
  40. 40.
    Carey JC, Greenbaum B, Hall BD. The OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects). Birth Defects Orig Artic Ser 1978;14(6B):253–263PubMedGoogle Scholar
  41. 41.
    Morimoto K, Takemoto O, Wakayama A. Tethered cord associated with anorectal malformation. Pediatr Neurosurg 2003;38:79–82CrossRefPubMedGoogle Scholar
  42. 42.
    Hayden PW, Chapman WH, Stevenson JK. Exstrophy of the cloaca. Am J Dis Child 1973;125:879–883PubMedGoogle Scholar
  43. 43.
    Hurwitz R, Manzoni G, Ransley P, Stephens F. Cloacal exstrophy: a report of 34 cases. J Urol 1987;138:1060–1064PubMedGoogle Scholar
  44. 44.
    Wyburn GM. The development of the infra-umbilical portion of the abdominal wall, with remarks on the aetiology of ectopia vesicae. J Anat 1937;71:201–231Google Scholar
  45. 45.
    Vermeij-Keers C, Hartwig NG, van der Werff JF. Embryonic development of the ventral body wall and its congenital malformations. Semin Pediatr Surg 1996;5:82–89PubMedGoogle Scholar
  46. 46.
    Kluth D, Lambrecht W. Current concepts in the embryology of anorectal malformations. Semin Pediatr Surg 1997;6:180–186PubMedGoogle Scholar
  47. 47.
    Nievelstein RA, van der Werff JF, Verbeek FJ, Valk J, Vermeij-Keers C. Normal and abnormal embryonic development of the anorectum in human embryos. Teratology 1998;57:70–78CrossRefPubMedGoogle Scholar
  48. 48.
    Paidas CN, Morreale RF, Holoski KM, Lund RE, Hutchins GM. Septation and differentiation of the embryonic human cloaca. J Pediatr Surg 1999;34:877–884CrossRefPubMedGoogle Scholar
  49. 49.
    Bruch SW, Adzick NS, Goldstein RB, Harrison MR. Challenging the embryogenesis of cloacal exstrophy. J Pediatr Surg 1996;31:768–770CrossRefPubMedGoogle Scholar
  50. 50.
    Lakshmanan Y, Bellin PB, Gilroy AM, Fung LCT. Antenatally diagnosed cloacal exstrophy variant with intravesical phallus in a twin pregnancy. Urology 2001;57:1178xii–1178xvCrossRefGoogle Scholar
  51. 51.
    Langer JC, Brennan B, Lappalainen RE, Caco CC, Winthrop AL, Hollenberg RD, et al. Cloacal exstrophy: prenatal diagnosis before rupture of the cloacal membrane. J Pediatr Surg 1992;27:1352–1355CrossRefPubMedGoogle Scholar
  52. 52.
    Mildenberger H, Kluth D, Dziuba M. Embryology of bladder exstrophy. J Pediatr Surg 1988;23:166–170PubMedGoogle Scholar
  53. 53.
    Koffler H, Aase J, Papile L-A, Coen R. Persistent cloaca with absent penis and anal atresia in one of identical twins. J Pediatr 1978;93:821–823PubMedGoogle Scholar
  54. 54.
    Wei X, Sulik KK. Pathogenesis of caudal dysgenesis/sirenomelia induced by Ochratoxin A in chick embryos. Teratology 1996;53:378–391CrossRefPubMedGoogle Scholar
  55. 55.
    Manner J, Kluth D. A chicken model to study the embryology of cloacal exstrophy. J Pediatr Surg 2003;38:678–681CrossRefPubMedGoogle Scholar
  56. 56.
    Manner J, Seidl W, Heinicke F, Hesse H. Teratogenic effects of suramin on the chick embryo. Anat Embryol 2003;206:229–237PubMedGoogle Scholar
  57. 57.
    Mo R, Kim JH, Zhang J, Chiang C, Hui C-C, Kim PCW. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol 2001;159:765–774PubMedGoogle Scholar
  58. 58.
    Thompson DJ, Molello JA, Strebing RJ, Dyke IL. Teratogenicity of adriamycin and daunomycin in the rat and rabbit. Teratology 1978;17:151–158CrossRefPubMedGoogle Scholar
  59. 59.
    Kramer R, Johnson M, Qureshi F, Jacques S, Yaron Y, Evans M. Concordance for cloacal dysgenesis. Fetal Diagn Ther 1997;12:279–282PubMedGoogle Scholar
  60. 60.
    Myrianthopoulos NC. Congenital malformations in twins: epidemiological survey. Birth Defects Orig Art Ser 1975;11:1–39Google Scholar
  61. 61.
    Schinzel A, Smith D, Miller J. Monozygotic twinning and structural defects. J Pediatr 1979;95:921–930PubMedGoogle Scholar
  62. 62.
    Spencer R. Conjoined Twins: Developmental Malformations and Clinical Implications. Baltimore: Johns Hopkins University Press, 2003Google Scholar
  63. 63.
    Cuschieri A, Group EW. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 2002;110:122–130CrossRefPubMedGoogle Scholar
  64. 64.
    Hall J. Twinning. Lancet 2003;362:735–743CrossRefPubMedGoogle Scholar
  65. 65.
    Stoeckel W. Lehbuch der Geburtschilfe. Jena: Gustav Fischer, 1945Google Scholar
  66. 66.
    Boklage C. The frequency and survival probability of natural twin conceptions. In: Keith L, Papiernik E, Keith D, et al, eds. Multiple Pregnancy: Epidemiology, Gestation and Perinatal Outcome. New York: Parthenon, 1995;41–50Google Scholar
  67. 67.
    Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346:725–730CrossRefPubMedGoogle Scholar
  68. 68.
    Nakano H, Kubota S, Koyanagi T, Taki I. The prognosis of multiple pregnancy assessed by ultrasonic tomography. Acta Obstet Gynaecol Jpn 1981;33:839–843PubMedGoogle Scholar
  69. 69.
    Sampson A, de Crespigny LC. Vanishing twins: the frequency of spontaneous fetal reduction of a twin pregnancy. Ultrasound Obstet Gynecol 1992;2:107–109CrossRefPubMedGoogle Scholar
  70. 70.
    Jackson J, Benirschke K. The recognition and significance of the vanishing twin. J Am Board Fam Pract 1989;2:58–63PubMedGoogle Scholar
  71. 71.
    Jauniaux E, Elkazen N, Leroy F, Wilkin P, Rodesch F, Hustin J. Clinical and morphologic aspects of the vanishing twin phenomenon. Obstet Gynecol 1988;72:577–581PubMedGoogle Scholar
  72. 72.
    Reddy KS, Petersen MB, Antonarakis SE, Blakemore KJ. The vanishing twin: an explanation for discordance between chorionic villus karyotype and fetal phenotype. Prenat Diagn 1991;11:679–684PubMedGoogle Scholar
  73. 73.
    Brodtkorb E, Myhr G, Gimse R. Is monochorionic twinning a risk factor for focal cortical dysgenesis? Acta Neurol Scand 2000;102:53–59CrossRefPubMedGoogle Scholar
  74. 74.
    Kapur RP, Mahony BS, Nyberg DA, Resta RG, Shepard TH. Sirenomelia associated with a “vanishing twin”. Teratology 1991;43:103–108CrossRefPubMedGoogle Scholar
  75. 75.
    Newton R, Casabonne D, Johnson A, Pharoah P. A case-control study of vanishing twin as a risk factor for cerebral palsy. Twin Res 2003;6:83–84CrossRefPubMedGoogle Scholar
  76. 76.
    Poenaru D, Uroz-Tristan J, Leclerc S, Murphy S, St-Vil D, Youssef S, et al. Minimally conjoined omphalopagi: a consistent spectrum of anomalies. J Pediatr Surg 1994;29:1236–1238CrossRefPubMedGoogle Scholar
  77. 77.
    Walton J, Gillis D, Giacomantonio J, Hayashi A, Lau H. Emergency separation of conjoined twins. J Pediatr Surg 1991;26:1337–1340CrossRefPubMedGoogle Scholar
  78. 78.
    Spencer R. Minimally united ischiopagus twins: infraumbilical union with cloacal anomalies. J Pediatri Surg 1996;31:1538–1545CrossRefGoogle Scholar
  79. 79.
    Smith D, Bartlett C, Harrah LM. Monozygotic twinning and the Duhamel anomalad (imperforate anus to sirenomelia): a nonrandom association between two aberrations in morphogenesis. Birth Defects Orig Art Ser 1976;12:53–63Google Scholar
  80. 80.
    Kapur RP, Jack RM, Siebert JR. Diamniotic placentation associated with omphalopagus conjoined twins: implications for a contemporary model of conjoined twinning. Am J Med Genet 1994;52:188–195CrossRefPubMedGoogle Scholar
  81. 81.
    Benirschke K, Kaufmann P. Pathology of the Human Placenta. New York: Springer-Verlag, 2000Google Scholar
  82. 82.
    Gilbert SF. Developmental Biology, 5th ed. Sunderland, MA: Sinauer Associates, 1997Google Scholar
  83. 83.
    Tarkowski AK, Wroblewska J. Development of blastomeres of mouse eggs isolated at the 4- and 8-cell stage. J Embryol Exp Morphol 1967;18:155–180PubMedGoogle Scholar
  84. 84.
    Sheen TC, Chen SR, Au HK, Chien YY, Wu KY, Tzeng CR. Herniated blastomere following chemically assisted hatching may result in monozygotic twins. Fertil Steril 2001;75:443–444CrossRefGoogle Scholar
  85. 85.
    Kaufman MH. The Atlas of Mouse Development. London: Academic Press, 1992Google Scholar
  86. 86.
    Popperl H, Schmidt C, Wilson V, Hume CR, Dodd J, Krumlauf R, et al. Misexpression of Cwnt8c in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm. Development 1997;124:2997–3005PubMedGoogle Scholar
  87. 87.
    Munro SS. Are monoovular avian twins always female. J Hered 1965;56:285–288PubMedGoogle Scholar
  88. 88.
    Spemann H. Embryonic Development and Induction. New York: Hafner Publishing, 1967Google Scholar
  89. 89.
    Stevens T, Siebert JR, Graham JJ, Beckwith JB. Parasitic conjoined twins, two cases, and their relation to limb morphogenesis. Teratology 1982;26:115–121CrossRefPubMedGoogle Scholar
  90. 90.
    Spencer R. Parasitic conjoined twins: external, internal (fetuses in fetu and teratomas), and detached (acardiacs). Clin Anat 2001;14:428–444CrossRefPubMedGoogle Scholar
  91. 91.
    Hsu YC, Gonda MA. Monozygotic twin formation in mouse embryos in vitro. Science 1980;209:605–606PubMedGoogle Scholar
  92. 92.
    Job CK, Sanchez RM, Kirchheimer WF, Hastings RC. Attempts to breed the nine-banded armadillo (Dasypus novemcinctus) in captivity—a preliminary report. Int J Lepr Other Mycobact Dis 1984;52:362–364PubMedGoogle Scholar
  93. 93.
    Newman HH, Patterson JT. The development of the nine-banded armadillo from the primitive streak stage to birth; with especial reference to the question of specific polyembryony. J Morphol 1910;21:359–424CrossRefGoogle Scholar
  94. 94.
    Baldwin VJ. Pathology of Multiple Pregnancy. New York: Springer-Verlag, 1994Google Scholar
  95. 95.
    Machin GA. Conjoined twins: implications for blastogenesis. Birth Defects Orig Art Ser 1993;29:141–179Google Scholar
  96. 96.
    Machin GA, Sperber GH. Lessons from conjoined twins. Am J Med Genet 1987;28:89–97CrossRefPubMedGoogle Scholar
  97. 97.
    Siebert JR, Machin GA, Sperber GH. Anatomic findings in dicephalic conjoined twins: implications for morphogenesis. Teratology 1989;40:305–310CrossRefPubMedGoogle Scholar
  98. 98.
    Sperber GH, Machin GA. Microscopic study of midline determinants in janiceps twins. Birth Defects Orig Art Ser 1987;23:243–275Google Scholar
  99. 99.
    Spencer R. Conjoined twins: theoretical embryologic basis. Teratology 1992;45:591–602CrossRefPubMedGoogle Scholar
  100. 100.
    Beckwith JB. Book review. Ped Dev Pathol 2003;6:361–364CrossRefGoogle Scholar
  101. 101.
    Messmer BJ, Hornchen H, Kosters C. Surgical separation of conjoined (Siamese) xiphopagus twins. Surgery 1981;89:622–625PubMedGoogle Scholar
  102. 102.
    Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, Frias JL. Exstrophy of the cloaca and exstrophy of the bladder: two different expressions of a primary developmental field defect. Am J Med Genet 2001;99:261–269CrossRefPubMedGoogle Scholar
  103. 103.
    O’Rahilly R, Muller F. Human Embryology & Teratology. New York: Wiley-Liss, 1992Google Scholar

Copyright information

© Society for Pediatric Pathology 2005

Authors and Affiliations

  • Joseph R. Siebert
    • 1
    • 2
  • Joe C. Rutledge
    • 1
    • 3
  • Raj P. Kapur
    • 1
    • 2
  1. 1.Department of Laboratories (A-6901)Children’s Hospital and Regional Medical CenterSeattleUSA
  2. 2.Department of PathologyUniversity of WashingtonSeattleUSA
  3. 3.Department of Laboratory MedicineUniversity of WashingtonSeattleUSA

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