Case Report An extremely rare case of classic complete caudal duplication: Dipygus Yasen Fayez Al Alayet, Ram Samujh1, Toijam Soni Lyngdoh1, Khizer Mansoor, Fawaz Al Kasim, Abdulaziz A. Al-Mustafa Department of Pediatric Surgery, King Saud Medical City Children Hospital, Shemisi-Riyadh, Kingdom of Saudi Arabia, 1Pediatric Surgery, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India Address for correspondence: Dr. Ram Samujh, Department of Pediatric Surgery, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh-160 012, India. E-mail: [email protected]
ABSTRACT Dipygus is a complete caudal duplication deformity in its severest form. The structures derived from the embryonic cloaca and notochords are duplicated to various extent. We report a male baby who presented to us with complete somatic and visceral duplication below the umbilical level associated with gastroschisis and imperforated anus. Staged surgical corrections were suggested and three out of the four stages were performed successfully.
Access this article online Website: www.jiaps.com DOI: 10.4103/0971-9261.136478 Quick Response Code:
KEY WORDS: Axin1 gene, caudal duplication syndrome, dipygus, monocephalus quadripus dibrachius, WNT pathway
INTRODUCTION Dipygus deformity is a severe and extreme form of caudal duplication where the body axis completely duplicates at the caudal end. Genetic, environmental or teratogenic factors are presumed to be implicated early in the intrauterine life thereby affecting the embryonic cloaca and notochord derivatives. This leads to uninhibited fission of the germinal disc at the caudal end and arrested fission rostrally. Only two cases of dipygus were reported in the English literature till date — the famous Francisco Lentini and Myrtle Corbin, who went on to live for many years begetting children.
CASE REPORT A full term baby boy born to a 2nd gravida mother was referred to our hospital at 4 hours after birth. Prenatally, diagnosis of dipygus could not be made, as the pregnancy was not supervised. Although difficult,
delivery was done through vaginal route when the baby was first noticed to have multiple anomalies including tetrapagus. There was no history of co-sanguinous marriage and no congenital anomaly was reported in the family. Examination of the baby immediately after birth revealed the presence of four lower limbs attached to double pelves, double perineum and double male external genitals [Figure 1]. Bilateral imperforate ani with flat bottom perineum and a common anterior abdominal wall defect (gastroschisis) were also noted. The middle pair of lower limbs appeared hypoplastic. Meconuria was seen from the left external meatus. Babygram X-ray showed segmentation of vertebral columns starting from the lower thoracic vertebrae caudally. Duplications of the lower three ribs on the left side, bisecting mid thoracic vertebrae were also noted. Medial halves of the pelvic bones appeared hypoplastic and fracture femur of the right medial lower limb were also seen. The attachment of left
Cite this article as: Al Alayet YF, Samujh R, Lyngdoh TS, Mansoor K, Al Kasim F, Al-Mustafa AA. An extremely rare case of classic complete caudal duplication: Dipygus. J Indian Assoc Pediatr Surg 2014;19:169-71. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
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Alayet, et al.: An extremely rare case of classic complete caudal duplication: Dipygus
pelvis to the vertebral column was higher than the right [Figure 2]. Further investigations with intravenous urography (IVU) showed two kidneys in normal position but there was duplication of the left pelvicalyceal system and the two ureters that were seen draining separately into two non-communicating urinary bladders. Out of the two imperforate ani, the left appeared to be high anomaly associated with rectovesical fistula and the right was of low type. The patient underwent multiple surgeries in stages. As a first stage, exploratory laparotomy was done which revealed the presence of a single liver, spleen, stomach, duodenum, jejunum and proximal ileum. There was complete duplication of the gastrointestinal tract starting from the terminal ileum till the rectum with one duplicated rectum opening into the left urinary bladder and the other maintaining its continuity on the right side leading to low anomaly anorectal malformation. The distal ileum, just proximal to duplication has a closed cystic dilatation and one of the bifurcated ileum conjoined distally has a narrow mouthed Meckels diverticulum. The two hemipelvis were found to be laterally located. Enteric cystostomy was done with primary closure of the abdominal wall defect (gastroschisis repair). Postoperative course was uneventful [Figure 3]. The 2nd operation was performed nine days later. The additional middle two lower limbs were amputated along with resection of the hypoplastic corresponding two pelvic bones and the lateral pelvis reapproximated to form a new pelvis. Further, Gallows traction was applied for subsequent two weeks.
Figure 1: Photograph showing quadripagus with associated gastroschisis
Figure 2: Babygram showing the duplications of the lower three ribs on the left side and bisection of vertebrae from mid thoracic caudally
At 6 weeks of age, the 3rd surgery was performed. Resection of the enteric cystic dilatation and the Meckels diverticulum bearing ileal segment and endto-end anastomosis between the terminal common ileum and proximal end of the right ileum along with total colectomy of the left colon and anoplasty of the right side was done. We decided to resect the left colon because it has rectovesical fistula, while the right side has low type imperforated anus without fistula, and so simple anoplasty was done. The baby was uneventfully discharged at 9th week in good general condition with advice to follow-up for the final stage surgery to be performed at 6 months of age. The plan was to resect the left external genitalia along with left hemibladder and left ureteric reimplantation. But at the 14th week, the baby was readmitted with diagnosis of aspiration pneumonia and septicemia and subsequently succumbed to septicemic shock 5 days later, which presumably was not related to the procedures. 170
Figure 3: Postoperative picture showing enteric cystostomy with primary closure of the abdominal wall defect
DISCUSSION Dipygus is also known as ‘teras catadidymum’, ‘monster twinned below’ or ‘Monocephalus quadripus
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
Alayet, et al.: An extremely rare case of classic complete caudal duplication: Dipygus
dibrachius’. It is the severest form of caudal duplication syndrome (CDS). Caudal duplication first described by Dominguez et al., in 1993 is defined as the association between malformations and duplications of the systems involving gastrointestinal, genitourinary and neural tube defects.[1] The exact incidence and embryonic pathophysiology is not known. Our index case has duplication of the gastrointestinal tract starting from the distal ileum till the anorectum associated with duplication of the lower genitourinary tract and complete duplication of the caudal notochord derivative. We believed that the entire constellation of anomalies in our case can be explained by the mechanism of defective regulation of embryonic gene expression. During embryogenesis, genes responsible for the basic developmental processes like progenitor cell proliferation, cell fate specification and control of asymmetric cell division are the WNT genes.[2] Mutations in WNT genes or its pathway components lead to specific developmental defects. Of the three WNT pathways, canonical pathway is responsible for WNT signaling, which plays a crucial role in controlling genetic programs of embryonic developmental defects. Genetic analysis in mice, particularly the use of conditional ‘loss and gain of ’ function mutations of β-catenin in various tissues and organs have implicated canonical WNT signals pathway in the maintenance and expansion of embryonic progenitor cells.[3] Moreover, WNT pathway, which is the signaling cascade of transcription factors, is also essential for the embryonic development of the cephalo-caudal axis especially the notochord, urogenitals and the intestines.[4] In rat embryos, homozygous mutations of the Axin1 gene, which is part of the inhibitory protein complex of the WNT pathway, result in the absence of the protein producing caudal axis duplication.[5] Similar studies by Oates et al., also implicated Axin1 gene mutation in causing caudal duplication in human monozygotic twins.[6] On the contrary, Kroes HY et al., had reported
normal 2nd monozygotic twins which signifies genetic event to occur after morula stage.[7] We believe that mutation of Axin1 gene or any of components of the WNT pathway may have caused the classical caudal duplication as in our index case. Similar case was also reported in British blue kittens with mutation of Axin1 gene.[8] It appears that, the theory of conditional ‘loss and gain of’ functional mutations of β-catenin can very well explained with the association of caudal duplication and caudal regression as reported by some authors, although unusual.[9]
CONCLUSION We conclude that the occurrence of these constellations of anomalies typical of caudal duplication is the result of disruption of regulation of WNT pathway and possibly involving Axin1 gene at the early part of embryogenesis.
REFERENCES 1. Dominguez R, Rott J, Castillo M, Pittaluga RR, Corriere JN Jr. Caudal duplication syndrome. Am J Dis Child 1993;147:1048-52. 2. Church VL, Francis-West P. Wnt signalling during limb development. Int J Dev Biol 2002;46:927-36. 3. Grigoryan T, Wend P, Klaus A, Birchmeier W. Deciphering the function of canonical Wnt signals in development and disease: Conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev 2008;22:2308-41. 4. Sporle R. Epaxial-adaxial-hypaxial regionalisation of the vertebrate somite: Evidence for a somitic organiser and a mirrorimage duplication. Dev Genes Evol 2001;211:198-217. 5. Salahshor S, Woodgett JR. The links between axin and carcinogenesis. J Clin Pathol 2005;58:225-36. 6. Oates NA, Van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, et al. Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet 2006;79:155-62. 7. Bansal G, Ghosh D, George U, Bhatti W. Unusual coexistence of caudal duplication and caudal regression syndromes. J Pediatr Surg 2011;46:256-8. 8. Seavers AM. Monocephalus dipygus parapagus: A suspected case of complete caudal duplication in a British Blue kitten. J Feline Med Surg 2009;11:330-1. 9. 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;112:390-3.
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
171
Copyright of Journal of Indian Association of Pediatric Surgeons is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
ABSTRACT Dipygus is a complete caudal duplication deformity in its severest form. The structures derived from the embryonic cloaca and notochords are duplicated to various extent. We report a male baby who presented to us with complete somatic and visceral duplication below the umbilical level associated with gastroschisis and imperforated anus. Staged surgical corrections were suggested and three out of the four stages were performed successfully.
Access this article online Website: www.jiaps.com DOI: 10.4103/0971-9261.136478 Quick Response Code:
KEY WORDS: Axin1 gene, caudal duplication syndrome, dipygus, monocephalus quadripus dibrachius, WNT pathway
INTRODUCTION Dipygus deformity is a severe and extreme form of caudal duplication where the body axis completely duplicates at the caudal end. Genetic, environmental or teratogenic factors are presumed to be implicated early in the intrauterine life thereby affecting the embryonic cloaca and notochord derivatives. This leads to uninhibited fission of the germinal disc at the caudal end and arrested fission rostrally. Only two cases of dipygus were reported in the English literature till date — the famous Francisco Lentini and Myrtle Corbin, who went on to live for many years begetting children.
CASE REPORT A full term baby boy born to a 2nd gravida mother was referred to our hospital at 4 hours after birth. Prenatally, diagnosis of dipygus could not be made, as the pregnancy was not supervised. Although difficult,
delivery was done through vaginal route when the baby was first noticed to have multiple anomalies including tetrapagus. There was no history of co-sanguinous marriage and no congenital anomaly was reported in the family. Examination of the baby immediately after birth revealed the presence of four lower limbs attached to double pelves, double perineum and double male external genitals [Figure 1]. Bilateral imperforate ani with flat bottom perineum and a common anterior abdominal wall defect (gastroschisis) were also noted. The middle pair of lower limbs appeared hypoplastic. Meconuria was seen from the left external meatus. Babygram X-ray showed segmentation of vertebral columns starting from the lower thoracic vertebrae caudally. Duplications of the lower three ribs on the left side, bisecting mid thoracic vertebrae were also noted. Medial halves of the pelvic bones appeared hypoplastic and fracture femur of the right medial lower limb were also seen. The attachment of left
Cite this article as: Al Alayet YF, Samujh R, Lyngdoh TS, Mansoor K, Al Kasim F, Al-Mustafa AA. An extremely rare case of classic complete caudal duplication: Dipygus. J Indian Assoc Pediatr Surg 2014;19:169-71. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
169
Alayet, et al.: An extremely rare case of classic complete caudal duplication: Dipygus
pelvis to the vertebral column was higher than the right [Figure 2]. Further investigations with intravenous urography (IVU) showed two kidneys in normal position but there was duplication of the left pelvicalyceal system and the two ureters that were seen draining separately into two non-communicating urinary bladders. Out of the two imperforate ani, the left appeared to be high anomaly associated with rectovesical fistula and the right was of low type. The patient underwent multiple surgeries in stages. As a first stage, exploratory laparotomy was done which revealed the presence of a single liver, spleen, stomach, duodenum, jejunum and proximal ileum. There was complete duplication of the gastrointestinal tract starting from the terminal ileum till the rectum with one duplicated rectum opening into the left urinary bladder and the other maintaining its continuity on the right side leading to low anomaly anorectal malformation. The distal ileum, just proximal to duplication has a closed cystic dilatation and one of the bifurcated ileum conjoined distally has a narrow mouthed Meckels diverticulum. The two hemipelvis were found to be laterally located. Enteric cystostomy was done with primary closure of the abdominal wall defect (gastroschisis repair). Postoperative course was uneventful [Figure 3]. The 2nd operation was performed nine days later. The additional middle two lower limbs were amputated along with resection of the hypoplastic corresponding two pelvic bones and the lateral pelvis reapproximated to form a new pelvis. Further, Gallows traction was applied for subsequent two weeks.
Figure 1: Photograph showing quadripagus with associated gastroschisis
Figure 2: Babygram showing the duplications of the lower three ribs on the left side and bisection of vertebrae from mid thoracic caudally
At 6 weeks of age, the 3rd surgery was performed. Resection of the enteric cystic dilatation and the Meckels diverticulum bearing ileal segment and endto-end anastomosis between the terminal common ileum and proximal end of the right ileum along with total colectomy of the left colon and anoplasty of the right side was done. We decided to resect the left colon because it has rectovesical fistula, while the right side has low type imperforated anus without fistula, and so simple anoplasty was done. The baby was uneventfully discharged at 9th week in good general condition with advice to follow-up for the final stage surgery to be performed at 6 months of age. The plan was to resect the left external genitalia along with left hemibladder and left ureteric reimplantation. But at the 14th week, the baby was readmitted with diagnosis of aspiration pneumonia and septicemia and subsequently succumbed to septicemic shock 5 days later, which presumably was not related to the procedures. 170
Figure 3: Postoperative picture showing enteric cystostomy with primary closure of the abdominal wall defect
DISCUSSION Dipygus is also known as ‘teras catadidymum’, ‘monster twinned below’ or ‘Monocephalus quadripus
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
Alayet, et al.: An extremely rare case of classic complete caudal duplication: Dipygus
dibrachius’. It is the severest form of caudal duplication syndrome (CDS). Caudal duplication first described by Dominguez et al., in 1993 is defined as the association between malformations and duplications of the systems involving gastrointestinal, genitourinary and neural tube defects.[1] The exact incidence and embryonic pathophysiology is not known. Our index case has duplication of the gastrointestinal tract starting from the distal ileum till the anorectum associated with duplication of the lower genitourinary tract and complete duplication of the caudal notochord derivative. We believed that the entire constellation of anomalies in our case can be explained by the mechanism of defective regulation of embryonic gene expression. During embryogenesis, genes responsible for the basic developmental processes like progenitor cell proliferation, cell fate specification and control of asymmetric cell division are the WNT genes.[2] Mutations in WNT genes or its pathway components lead to specific developmental defects. Of the three WNT pathways, canonical pathway is responsible for WNT signaling, which plays a crucial role in controlling genetic programs of embryonic developmental defects. Genetic analysis in mice, particularly the use of conditional ‘loss and gain of ’ function mutations of β-catenin in various tissues and organs have implicated canonical WNT signals pathway in the maintenance and expansion of embryonic progenitor cells.[3] Moreover, WNT pathway, which is the signaling cascade of transcription factors, is also essential for the embryonic development of the cephalo-caudal axis especially the notochord, urogenitals and the intestines.[4] In rat embryos, homozygous mutations of the Axin1 gene, which is part of the inhibitory protein complex of the WNT pathway, result in the absence of the protein producing caudal axis duplication.[5] Similar studies by Oates et al., also implicated Axin1 gene mutation in causing caudal duplication in human monozygotic twins.[6] On the contrary, Kroes HY et al., had reported
normal 2nd monozygotic twins which signifies genetic event to occur after morula stage.[7] We believe that mutation of Axin1 gene or any of components of the WNT pathway may have caused the classical caudal duplication as in our index case. Similar case was also reported in British blue kittens with mutation of Axin1 gene.[8] It appears that, the theory of conditional ‘loss and gain of’ functional mutations of β-catenin can very well explained with the association of caudal duplication and caudal regression as reported by some authors, although unusual.[9]
CONCLUSION We conclude that the occurrence of these constellations of anomalies typical of caudal duplication is the result of disruption of regulation of WNT pathway and possibly involving Axin1 gene at the early part of embryogenesis.
REFERENCES 1. Dominguez R, Rott J, Castillo M, Pittaluga RR, Corriere JN Jr. Caudal duplication syndrome. Am J Dis Child 1993;147:1048-52. 2. Church VL, Francis-West P. Wnt signalling during limb development. Int J Dev Biol 2002;46:927-36. 3. Grigoryan T, Wend P, Klaus A, Birchmeier W. Deciphering the function of canonical Wnt signals in development and disease: Conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev 2008;22:2308-41. 4. Sporle R. Epaxial-adaxial-hypaxial regionalisation of the vertebrate somite: Evidence for a somitic organiser and a mirrorimage duplication. Dev Genes Evol 2001;211:198-217. 5. Salahshor S, Woodgett JR. The links between axin and carcinogenesis. J Clin Pathol 2005;58:225-36. 6. Oates NA, Van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, et al. Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet 2006;79:155-62. 7. Bansal G, Ghosh D, George U, Bhatti W. Unusual coexistence of caudal duplication and caudal regression syndromes. J Pediatr Surg 2011;46:256-8. 8. Seavers AM. Monocephalus dipygus parapagus: A suspected case of complete caudal duplication in a British Blue kitten. J Feline Med Surg 2009;11:330-1. 9. 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;112:390-3.
Journal of Indian Association of Pediatric Surgeons / Jul-Sep 2014 / Vol 19 / Issue 3
171
Copyright of Journal of Indian Association of Pediatric Surgeons is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
