26 Short case report
Caudal duplication with multicystic dysplastic kidney: a case report Constanza García-Delgadoa, Paola Mendelsberg-Fishbeina, Fernando González-Ledónb, Rodrigo Moreno-Salgadoa, María E. Blanco-Aguirrec and Verónica F. Morán-Barrosoa Clinical Dysmorphology 2015, 24:26–28 a
b
Departments of Genetics, Urology, Hospital Infantil de México Federico Gómez, Mexico City and cDepartment of Genetics, Hospital Materno Perinatal ‘Mónica Pretelini Saenz’, ISEM, Toluca, Mexico
Correspondence to Verónica F. Morán-Barroso, PhD, Department of Genetics, Hospital Infantil de México Federico Gómez, Calle Dr. Márquez 162, Col. Doctores, Del. Cuauhtémoc, C.P. 06720, Distrito Federal, México Tel: + 52 55 52 28 99 17 x2037; fax: + 52 55 57610270; e-mails: [email protected] and [email protected] Received 1 April 2014 Accepted 9 September 2014
Key features Female external genitalia duplication Cloacal anorectal malformation Parallel colon duplication, from cecum to cloaca Lumbosacral diastematomyelia with a tethered spinal cord Multicystic dysplastic right kidney
Short clinical summary The patient is a now a 2-year-old female product of a first pregnancy. Her parents are young, healthy, and nonconsanguineous. She has a younger sister who is apparently healthy and a paternal half-brother who died at 1 day of age apparently due to nonspecified pulmonary abnormalities. While pregnant with the proband the mother underwent normal prenatal care, and no exposure to teratogenic substances was recorded. Oligohydramnios was observed on a third trimester routine prenatal ultrasonographic study. The patient was born by Cesarean section at 38 weeks of gestation with a weight of 3260 g and a length of 47 cm, which correspond to the 50th and 25th percentile, respectively. At birth, female duplicated external genitalia were noticed. Because of genitourinary and anorectal malformations, bladder and colonic catheters were placed and she was referred to our institution, where laparotomy with surgical remodeling of previous interventions was performed. Colon duplication from the ascending colon to the cloaca was reported on surgical findings.
Investigations An abdominal computed tomographic scan with threedimensional reconstruction, cystographic studies, and cystoscopy were performed; the resultant findings included the following: parallel colonic duplication with a normal and solitary cecal appendix; bladder and hydrometrocolpos; lumbosacral diastematomyelia beginning at L5 with a tethered spinal cord; and multiple cysts on the right kidney (Figs 1 and 2). In addition, a renal gammagram study was performed showing functional exclusion 0962-8827 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
of the right kidney. An echocardiogram revealed anatomically normal heart structures. Cytogenetic analysis with GTG banding karyotype result was 46,XX. She has undergone multiple surgical interventions to improve her condition and quality of life.
Discussion Caudal duplication is a rare anomaly characterized by partial or total duplication of caudal structures such as the colon, rectus, genitourinary tract, abdominal wall, and vertebral column; in a few cases accessory inferior limbs are present (Chadha et al., 1993; Arnone et al., 2011). Dominguez et al. (1993) proposed the term caudal duplication syndrome to describe the association between these genitourinary, gastrointestinal, and distal neural tube malformations. As the phenotype is widely variable in each case, a complete definition is still under discussion (Ravitch, 1953; Bajpai et al., 2004; Wegman-Ostrosky et al., 2012; Sur et al., 2013). The etiology for this type of anomalies is unknown but a sporadic pattern of presentation is considered. The proposed theories include abnormal twining and epigenetic effects being the principal candidate gene AXIN1 (Oates et al., 2006). Previously reported studies have demonstrated methylation pattern anomalies in the AXIN1 gene on discordant monocygotic twins (Oates et al., 2006) and murine models with AXIN1 mutations presented with a bifid tail. AXIN1 is an inhibitor of the WNT1 signaling pathway and works in the β-catenin degradation pathway (Rodova et al., 2002; MacDonald et al., 2009). These data are interesting as they might show an association between the presentation of caudal duplication anomaly and multicystic dysplastic kidney (MCDK) disease if this pathway is altered. A unilateral MCDK was observed in our patient on the right side. MCDK has an incidence of 1 : 4300 live births and is usually unilateral, most commonly occurring in the left kidney (Cooper et al., 2013). There is no family history of kidney cysts and no consanguinity was reported. DOI: 10.1097/MCD.0000000000000060
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Caudal duplication with MCDK García-Delgado et al. 27
Fig. 1
Phenotypically female external genitalia showing duplication of the structures in the patient.
Commonly, the MCDK represents the final stage of a prenatal severe urinary obstruction and is the most frequent cause of unilateral kidney exclusion associated with multiple cysts in children (Okada et al., 2003). We present a patient with caudal duplication and cloacal anorectal malformation. These anomalies have been previously described in a few cases in the same patient (Arnone et al., 2011). Multiple cysts on the right kidney were also found; this malformation has not been reported previously as part of the caudal duplication syndrome, but considering the AXIN1 gene function it can be taken into consideration for supporting the etiology theory for caudal duplication syndrome. We consider that this case broadens the phenotypic clinical spectrum of the caudal duplication syndrome.
Fig. 2
CT scan with three-dimensional reconstruction of thoracic and abdominal regions. (a) Lumbosacral diastematomyelia (arrow head). (b) Duplication of abdominal structures. (c) Cystographic studies showing the bladder (anterior) and hydrometrocolpos (indicated by the Foley probe). (d) CT scan of the abdominal region with colonic duplication and MCDK on the right (arrows). CT, computed tomography; MCDK, multicystic dysplastic kidney.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
28 Clinical Dysmorphology 2015, Vol 24 No 1
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Arnone K, Cloutier J, Bolduc S (2011). Persistent cloaca and partial caudal duplication: a case report. Urology 78:431–433. Bajpai M, Das K, Gupta AK (2004). Caudal duplication syndrome: more evidence for theory of caudal twinning. J Pediatr Surg 39:223–225. Chadha R, Dhar A, Bagga D, Malhotra CJ, Taneja SB (1993). An unusual form of caudal duplication (dipygus). J Pediatr Surg 28:728–730. Cooper CJ, Said S, Khalillullah S, Salameh HJ, Hernandez GT (2013). Multicystic dysplastic kidney complicated by pyelonephritis. Am J Case Rep 14:412–415. Dominguez R, Rott J, Castillo M, Pittaluga RR, Corriere JN Jr (1993). Caudal duplication syndrome. Am J Dis Child 147:1048–1052. MacDonald BT, Tamai K, He X (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26.
Oates NA, van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, et al. (2006). Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet 79:155–162. Okada T, Yoshida H, Matsunaga T, Kouchi K, Ohtsuka Y, Saitou T, et al. (2003). Multicystic dysplastic kidney detected by prenatal ultrasonography: natural history and conservative management. Pediatr Surg Int 19: 207–210. Ravitch MM (1953). Hind gut duplication; doubling of colon and genital urinary tracts. Ann Surg 137:588–601. Rodova M, Islam MR, Maser RL, Calvet JP (2002). The polycystic kidney disease1 promoter is a target of the beta-catenin/T-cell factor pathway. J Biol Chem 277:29577–29583. Sur A, Sardar SK, Paria A (2013). Caudal duplication syndrome. J Clin Neonatol 2:101–102. Wegman-Ostrosky T, Sánchez-Corona J, Alférez-Morfín R, González Ulloa BE, Ramírez-Dueñas Mde L, Dávalos IP (2012). Caudal duplication: case report. Cir Cir 80:375–378.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Caudal duplication with multicystic dysplastic kidney: a case report Constanza García-Delgadoa, Paola Mendelsberg-Fishbeina, Fernando González-Ledónb, Rodrigo Moreno-Salgadoa, María E. Blanco-Aguirrec and Verónica F. Morán-Barrosoa Clinical Dysmorphology 2015, 24:26–28 a
b
Departments of Genetics, Urology, Hospital Infantil de México Federico Gómez, Mexico City and cDepartment of Genetics, Hospital Materno Perinatal ‘Mónica Pretelini Saenz’, ISEM, Toluca, Mexico
Correspondence to Verónica F. Morán-Barroso, PhD, Department of Genetics, Hospital Infantil de México Federico Gómez, Calle Dr. Márquez 162, Col. Doctores, Del. Cuauhtémoc, C.P. 06720, Distrito Federal, México Tel: + 52 55 52 28 99 17 x2037; fax: + 52 55 57610270; e-mails: [email protected] and [email protected] Received 1 April 2014 Accepted 9 September 2014
Key features Female external genitalia duplication Cloacal anorectal malformation Parallel colon duplication, from cecum to cloaca Lumbosacral diastematomyelia with a tethered spinal cord Multicystic dysplastic right kidney
Short clinical summary The patient is a now a 2-year-old female product of a first pregnancy. Her parents are young, healthy, and nonconsanguineous. She has a younger sister who is apparently healthy and a paternal half-brother who died at 1 day of age apparently due to nonspecified pulmonary abnormalities. While pregnant with the proband the mother underwent normal prenatal care, and no exposure to teratogenic substances was recorded. Oligohydramnios was observed on a third trimester routine prenatal ultrasonographic study. The patient was born by Cesarean section at 38 weeks of gestation with a weight of 3260 g and a length of 47 cm, which correspond to the 50th and 25th percentile, respectively. At birth, female duplicated external genitalia were noticed. Because of genitourinary and anorectal malformations, bladder and colonic catheters were placed and she was referred to our institution, where laparotomy with surgical remodeling of previous interventions was performed. Colon duplication from the ascending colon to the cloaca was reported on surgical findings.
Investigations An abdominal computed tomographic scan with threedimensional reconstruction, cystographic studies, and cystoscopy were performed; the resultant findings included the following: parallel colonic duplication with a normal and solitary cecal appendix; bladder and hydrometrocolpos; lumbosacral diastematomyelia beginning at L5 with a tethered spinal cord; and multiple cysts on the right kidney (Figs 1 and 2). In addition, a renal gammagram study was performed showing functional exclusion 0962-8827 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
of the right kidney. An echocardiogram revealed anatomically normal heart structures. Cytogenetic analysis with GTG banding karyotype result was 46,XX. She has undergone multiple surgical interventions to improve her condition and quality of life.
Discussion Caudal duplication is a rare anomaly characterized by partial or total duplication of caudal structures such as the colon, rectus, genitourinary tract, abdominal wall, and vertebral column; in a few cases accessory inferior limbs are present (Chadha et al., 1993; Arnone et al., 2011). Dominguez et al. (1993) proposed the term caudal duplication syndrome to describe the association between these genitourinary, gastrointestinal, and distal neural tube malformations. As the phenotype is widely variable in each case, a complete definition is still under discussion (Ravitch, 1953; Bajpai et al., 2004; Wegman-Ostrosky et al., 2012; Sur et al., 2013). The etiology for this type of anomalies is unknown but a sporadic pattern of presentation is considered. The proposed theories include abnormal twining and epigenetic effects being the principal candidate gene AXIN1 (Oates et al., 2006). Previously reported studies have demonstrated methylation pattern anomalies in the AXIN1 gene on discordant monocygotic twins (Oates et al., 2006) and murine models with AXIN1 mutations presented with a bifid tail. AXIN1 is an inhibitor of the WNT1 signaling pathway and works in the β-catenin degradation pathway (Rodova et al., 2002; MacDonald et al., 2009). These data are interesting as they might show an association between the presentation of caudal duplication anomaly and multicystic dysplastic kidney (MCDK) disease if this pathway is altered. A unilateral MCDK was observed in our patient on the right side. MCDK has an incidence of 1 : 4300 live births and is usually unilateral, most commonly occurring in the left kidney (Cooper et al., 2013). There is no family history of kidney cysts and no consanguinity was reported. DOI: 10.1097/MCD.0000000000000060
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Caudal duplication with MCDK García-Delgado et al. 27
Fig. 1
Phenotypically female external genitalia showing duplication of the structures in the patient.
Commonly, the MCDK represents the final stage of a prenatal severe urinary obstruction and is the most frequent cause of unilateral kidney exclusion associated with multiple cysts in children (Okada et al., 2003). We present a patient with caudal duplication and cloacal anorectal malformation. These anomalies have been previously described in a few cases in the same patient (Arnone et al., 2011). Multiple cysts on the right kidney were also found; this malformation has not been reported previously as part of the caudal duplication syndrome, but considering the AXIN1 gene function it can be taken into consideration for supporting the etiology theory for caudal duplication syndrome. We consider that this case broadens the phenotypic clinical spectrum of the caudal duplication syndrome.
Fig. 2
CT scan with three-dimensional reconstruction of thoracic and abdominal regions. (a) Lumbosacral diastematomyelia (arrow head). (b) Duplication of abdominal structures. (c) Cystographic studies showing the bladder (anterior) and hydrometrocolpos (indicated by the Foley probe). (d) CT scan of the abdominal region with colonic duplication and MCDK on the right (arrows). CT, computed tomography; MCDK, multicystic dysplastic kidney.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
28 Clinical Dysmorphology 2015, Vol 24 No 1
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Arnone K, Cloutier J, Bolduc S (2011). Persistent cloaca and partial caudal duplication: a case report. Urology 78:431–433. Bajpai M, Das K, Gupta AK (2004). Caudal duplication syndrome: more evidence for theory of caudal twinning. J Pediatr Surg 39:223–225. Chadha R, Dhar A, Bagga D, Malhotra CJ, Taneja SB (1993). An unusual form of caudal duplication (dipygus). J Pediatr Surg 28:728–730. Cooper CJ, Said S, Khalillullah S, Salameh HJ, Hernandez GT (2013). Multicystic dysplastic kidney complicated by pyelonephritis. Am J Case Rep 14:412–415. Dominguez R, Rott J, Castillo M, Pittaluga RR, Corriere JN Jr (1993). Caudal duplication syndrome. Am J Dis Child 147:1048–1052. MacDonald BT, Tamai K, He X (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26.
Oates NA, van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, et al. (2006). Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet 79:155–162. Okada T, Yoshida H, Matsunaga T, Kouchi K, Ohtsuka Y, Saitou T, et al. (2003). Multicystic dysplastic kidney detected by prenatal ultrasonography: natural history and conservative management. Pediatr Surg Int 19: 207–210. Ravitch MM (1953). Hind gut duplication; doubling of colon and genital urinary tracts. Ann Surg 137:588–601. Rodova M, Islam MR, Maser RL, Calvet JP (2002). The polycystic kidney disease1 promoter is a target of the beta-catenin/T-cell factor pathway. J Biol Chem 277:29577–29583. Sur A, Sardar SK, Paria A (2013). Caudal duplication syndrome. J Clin Neonatol 2:101–102. Wegman-Ostrosky T, Sánchez-Corona J, Alférez-Morfín R, González Ulloa BE, Ramírez-Dueñas Mde L, Dávalos IP (2012). Caudal duplication: case report. Cir Cir 80:375–378.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
