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Congenital Anomalies of the Kidneys

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Pediatric Nephrology

Abstract

Congenital kidney anomalies are the result of embryonic maldevelopment that dates back to the fifth gestational week in humans. At this time-point, the metanephric mesenchyme, which originates from the nephrogenic cord, and the outgrowing ureteric bud, which originates from the nephric duct, display highly coordinated spatiotemporal interactions that result in the development of the kidney and the adjacent urinary tract (see Chap. 1, “Pre-natal Development of the Kidneys and Urinary Tract”). Disturbances in the molecular communication between the metanephric mesenchyme and the ureteric bud give rise to a spectrum of kidney abnormalities that differ from one another depending on the timing and/or location of the disturbance. Based on the location of the disturbance, congenital kidney anomalies can arise as unilateral or bilateral defects, or they can result in the formation of ectopic kidney tissue. Early perturbations lead to the complete absence of kidney tissue, whereas later events may result in an underdeveloped kidney that is hypoplastic or dysplastic or in a kidney with reduced nephron number. Many of these spatiotemporal disturbances are caused by genetic, epigenetic and/or environmental factors that are also involved in the development of other organs. Therefore, congenital kidney defects may present in conjunction with extrarenal defects or be part of a well-defined clinical syndrome.

In this chapter, we discuss the phenotypic spectrum of human congenital kidney defects that encompasses unilateral renal agenesis (URA), bilateral renal agenesis, renal hypoplasia, renal dysplasia, multicystic dysplastic kidney (MCDK) as well as ectopic kidney tissue, kidney fusion defects (such as crossed fused ectopia and horseshoe kidney), and finally, duplication of the kidney. The clinical presentation, their management, and the syndromes that are associated with congenital kidney anomalies will be discussed. Finally, we provide a state-of-the-art overview of the molecular mechanisms that give rise to congenital kidney anomalies.

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References

  1. Roodhooft AM, Birnholz JC, Holmes LB. Familial nature of congenital absence and severe dysgenesis of both kidneys. N Engl J Med. 1984;310(21):1341–5.

    Article  CAS  PubMed  Google Scholar 

  2. Bankier A, et al. A pedigree study of perinatally lethal renal disease. J Med Genet. 1985;22(2):104–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Humbert C, et al. Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans. Am J Hum Genet. 2014;94(2):288–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Barak H, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012;22(6):1191–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Colquhoun-Kerr JS, et al. X-linked Kallmann syndrome and renal agenesis occurring together and independently in a large Australian family. Am J Med Genet. 1999;83(1):23–7.

    Article  CAS  PubMed  Google Scholar 

  6. Jeanpierre C, et al. RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet. 2011;48(7):497–504.

    Article  CAS  PubMed  Google Scholar 

  7. Dogan CS, Torun Bayram M. Renal outcome of children with unilateral renal agenesis. Turk J Pediatr. 2013;55(6):612–5.

    PubMed  Google Scholar 

  8. Westland R, et al. Unilateral renal agenesis: a systematic review on associated anomalies and renal injury. Nephrol Dial Transplant. 2013;28(7):1844–55.

    Article  PubMed  Google Scholar 

  9. Schreuder MF, et al. Hypertension and microalbuminuria in children with congenital solitary kidneys. J Paediatr Child Health. 2008;44(6):363–8.

    Article  PubMed  Google Scholar 

  10. van Vuuren SH, et al. Compensatory enlargement of a solitary functioning kidney during fetal development. Ultrasound Obstet Gynecol. 2012a;40(6):665–8.

    Article  PubMed  Google Scholar 

  11. Cho JY, et al. Measurement of compensatory hyperplasia of the contralateral kidney: usefulness for differential diagnosis of fetal unilateral empty renal fossa. Ultrasound Obstet Gynecol. 2009;34(5):515–20.

    Article  CAS  PubMed  Google Scholar 

  12. Yulia A, Winyard P. Management of antenatally detected kidney malformations. Early Hum Dev. 2018;126:38–46.

    Article  CAS  PubMed  Google Scholar 

  13. Schreuder MF, Westland R, van Wijk JA. Unilateral multicystic dysplastic kidney: a meta-analysis of observational studies on the incidence, associated urinary tract malformations and the contralateral kidney. Nephrol Dial Transplant. 2009;24(6):1810–8.

    Article  PubMed  Google Scholar 

  14. Dogan CS, Torun-Bayram M, Aybar MD. Unilateral multicystic dysplastic kidney in children. Turk J Pediatr. 2014;56(1):75–9.

    PubMed  Google Scholar 

  15. Sanna-Cherchi S, et al. Renal outcome in patients with congenital anomalies of the kidney and urinary tract. Kidney Int. 2009;76(5):528–33.

    Article  PubMed  Google Scholar 

  16. Sharada S, et al. Multicystic dysplastic kidney: a retrospective study. Indian Pediatr. 2014;51(8):641–3.

    Article  PubMed  Google Scholar 

  17. Hains DS, et al. Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol. 2009;24(2):233–41.

    Article  PubMed  Google Scholar 

  18. Spira EM, et al. Sonographic long-term study: paediatric growth charts for single kidneys. Arch Dis Child. 2009;94(9):693–8.

    Article  CAS  PubMed  Google Scholar 

  19. Eickmeyer AB, et al. The natural history of the multicystic dysplastic kidney – is limited follow-up warranted? J Pediatr Urol. 2014;10(4):655–61.

    Article  CAS  PubMed  Google Scholar 

  20. Caruana G, et al. Copy-number variation associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol. 2015;30(3):487–95.

    Article  PubMed  Google Scholar 

  21. Hasui M, et al. Different phenotypes of HNF1ss deletion mutants in familial multicystic dysplastic kidneys. Clin Nephrol. 2013;79(6):484–7.

    Article  CAS  PubMed  Google Scholar 

  22. Verghese P, Miyashita Y. Neonatal polycystic kidney disease. Clin Perinatol. 2014;41(3):543–60.

    Article  PubMed  Google Scholar 

  23. Avni FE, et al. Imaging and classification of congenital cystic renal diseases. AJR Am J Roentgenol. 2012;198(5):1004–13.

    Article  PubMed  Google Scholar 

  24. Arora V, et al. Co-inheritance of pathogenic variants in PKD1 and PKD2 genes presenting as severe antenatal phenotype of autosomal dominant polycystic kidney disease. Eur J Med Genet. 2020;63(3):103734.

    Article  PubMed  Google Scholar 

  25. Decramer S, et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol. 2007;18(3):923–33.

    Article  CAS  PubMed  Google Scholar 

  26. Gleason PE, et al. Hydronephrosis in renal ectopia: incidence, etiology and significance. J Urol. 1994;151(6):1660–1.

    Article  CAS  PubMed  Google Scholar 

  27. Glenn JF. Analysis of 51 patients with horseshoe kidney. N Engl J Med. 1959;261:684–7.

    Article  CAS  PubMed  Google Scholar 

  28. Cascio S, et al. Vesicoureteral reflux and ureteropelvic junction obstruction in children with horseshoe kidney: treatment and outcome. J Urol. 2002;167(6):2566–8.

    Article  CAS  PubMed  Google Scholar 

  29. Boatman DL, Kolln CP, Flocks RH. Congenital anomalies associated with horseshoe kidney. J Urol. 1972;107(2):205–7.

    Article  CAS  PubMed  Google Scholar 

  30. Neville H, et al. The occurrence of Wilms tumor in horseshoe kidneys: a report from the National Wilms Tumor Study Group (NWTSG). J Pediatr Surg. 2002;37(8):1134–7.

    Article  PubMed  Google Scholar 

  31. Bilge I, et al. Frequency of renal malformations in Turner syndrome: analysis of 82 Turkish children. Pediatr Nephrol. 2000;14(12):1111–4.

    Article  CAS  PubMed  Google Scholar 

  32. Zuckerman JM, Upadhyay J. Crossed-fused testicular ectopia: a case for the use of laparoscopy to evaluate nonpalpable testicles. J Pediatr. 2012;160(5):879.

    Article  PubMed  Google Scholar 

  33. Brace RA, Wolf EJ. Normal amniotic fluid volume changes throughout pregnancy. Am J Obstet Gynecol. 1989;161(2):382–8.

    Article  CAS  PubMed  Google Scholar 

  34. Hebbar S, et al. Reference ranges of amniotic fluid index in late third trimester of pregnancy: what should the optimal interval between two ultrasound examinations be? J Pregnancy. 2015;2015:319204.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Moore TR, Cayle JE. The amniotic fluid index in normal human pregnancy. Am J Obstet Gynecol. 1990;162(5):1168–73.

    Article  CAS  PubMed  Google Scholar 

  36. van Vuuren SH, et al. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. Ultrasound Obstet Gynecol. 2012b;40(6):659–64.

    Article  PubMed  Google Scholar 

  37. Richter-Rodier M, et al. Ultrasound screening strategies for the diagnosis of congenital anomalies of the kidney and urinary tract. Ultraschall Med. 2012;33(7):E333–8.

    Article  CAS  PubMed  Google Scholar 

  38. Macumber I, Schwartz S, Leca N. Maternal obesity is associated with congenital anomalies of the kidney and urinary tract in offspring. Pediatr Nephrol. 2017;32(4):635–42.

    Article  PubMed  Google Scholar 

  39. Chalouhi GE, et al. The use of fetal MRI for renal and urogenital tract anomalies. Prenat Diagn. 2020;40(1):100–9.

    Article  PubMed  Google Scholar 

  40. Fazecas TM, et al. Applicability of magnetic resonance imaging in the assessment of fetal urinary tract malformations. Can Assoc Radiol J. 2019;70(1):83–95.

    Article  PubMed  Google Scholar 

  41. Melo BF, et al. Early risk factors for neonatal mortality in CAKUT: analysis of 524 affected newborns. Pediatr Nephrol. 2012;27(6):965–72.

    Article  PubMed  Google Scholar 

  42. Policiano C, et al. Ultrasound antenatal detection of urinary tract anomalies in the last decade: outcome and prognosis. J Matern Fetal Neonatal Med. 2015;28(8):959–63.

    Article  PubMed  Google Scholar 

  43. Tsatsaris V, et al. Prenatal diagnosis of bilateral isolated fetal hyperechogenic kidneys. Is it possible to predict long term outcome? BJOG. 2002;109(12):1388–93.

    Article  CAS  PubMed  Google Scholar 

  44. Morris RK, et al. Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy. BJOG. 2009;116(10):1290–9.

    Article  CAS  PubMed  Google Scholar 

  45. Klaassen I, et al. Antenatal oligohydramnios of renal origin: long-term outcome. Nephrol Dial Transplant. 2007;22(2):432–9.

    Article  PubMed  Google Scholar 

  46. Mehler K, et al. Respiratory and general outcome in neonates with renal oligohydramnios – a single-centre experience. Nephrol Dial Transplant. 2011;26(11):3514–22.

    Article  PubMed  Google Scholar 

  47. Askenazi SS, Perlman M. Pulmonary hypoplasia: lung weight and radial alveolar count as criteria of diagnosis. Arch Dis Child. 1979;54(8):614–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Aulbert W, Kemper MJ. Severe antenatally diagnosed renal disorders: background, prognosis and practical approach. Pediatr Nephrol. 2016;31(4):563–74.

    Article  PubMed  Google Scholar 

  49. Spaggiari E, et al. Outcome following prenatal diagnosis of severe bilateral renal hypoplasia. Prenat Diagn. 2013;33(12):1167–72.

    Article  CAS  PubMed  Google Scholar 

  50. Klein J, Buffin-Meyer B, Boizard F, Moussaoui N, Lescat O, Breuil B, Fedou C, Feuillet G, Casemayou A, Neau E, Hindryckx A, Decatte L, Levtchenko E, Raaijmakers A, Vayssière C, Goua V, Lucas C, Perrotin F, Cloarec S, Benachi A, Manca-Pellissier MC, Delmas HL, Bessenay L, Le Vaillant C, Allain-Launay E, Gondry J, Boudailliez B, Simon E, Prieur F, Lavocat MP, Saliou AH, De Parscau L, Bidat L, Noel C, Floch C, Bourdat-Michel G, Favre R, Weingertner AS, Oury JF, Baudouin V, Bory JP, Pietrement C, Fiorenza M, Massardier J, Kessler S, Lounis N, Auriol FC, Marcorelles P, Collardeau-Frachon S, Zürbig P, Mischak H, Magalhñes P, Batut J, Blader P, Saulnier Blache JS, Bascands JL, Schaefer F, Decramer S, Schanstra JP; BIOMAN consortium. Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease. Kidney Int. 2021;99(3):737–749. https://doi.org/10.1016/j.kint.2020.06.043. Epub 2020 Aug 1. PMID: 32750455.

  51. Oliveira EA, et al. Outcome of fetal urinary tract anomalies associated with multiple malformations and chromosomal abnormalities. Prenat Diagn. 2001;21(2):129–34.

    Article  CAS  PubMed  Google Scholar 

  52. Dionne JM, d’Agincourt-Canning L. Sustaining life or prolonging dying? Appropriate choice of conservative care for children in end-stage renal disease: an ethical framework. Pediatr Nephrol. 2015;30(10):1761–9.

    Article  PubMed  Google Scholar 

  53. Talati AN, Webster CM, Vora NL. Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT). Prenat Diagn. 2019;39(9):679–92.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Warring SK, et al. Serial amnioinfusion as regenerative therapy for pulmonary hypoplasia in fetuses with intrauterine renal failure or severe renal anomalies: systematic review and future perspectives. Mayo Clin Proc Innov Qual Outcomes. 2020;4(4):391–409.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Sanna-Cherchi S, et al. Genetic basis of human congenital anomalies of the kidney and urinary tract. J Clin Invest. 2018;128(1):4–15.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Rasouly HM, et al. The burden of candidate pathogenic variants for kidney and genitourinary disorders emerging from exome sequencing. Ann Intern Med. 2019;170(1):11–21.

    Article  PubMed  Google Scholar 

  57. Westland R, Renkema KY, Knoers NVAM. Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract. Clin J Am Soc Nephrol. 2020;16(1):128–137. https://doi.org/10.2215/CJN.14661119. Epub 2020 Apr 20. PMID: 32312792; PMCID: PMC7792653.

  58. Weber S, et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol. 2006;17(10):2864–70.

    Article  CAS  PubMed  Google Scholar 

  59. Horikawa Y, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet. 1997;17(4):384–5.

    Article  CAS  PubMed  Google Scholar 

  60. Chen YZ, et al. Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5. Chin Med J. 2010;123(22):3326–33.

    CAS  PubMed  Google Scholar 

  61. Faguer S, et al. The HNF1B score is a simple tool to select patients for HNF1B gene analysis. Kidney Int. 2014;86(5):1007–15.

    Article  CAS  PubMed  Google Scholar 

  62. Sanyanusin P, et al. Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet. 1995;9(4):358–64.

    Article  CAS  PubMed  Google Scholar 

  63. Vivante A, et al. Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children. Pediatr Nephrol. 2019;34(9):1607–13.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Brophy PD, et al. A gene implicated in activation of retinoic acid receptor targets is a novel renal agenesis gene in humans. Genetics. 2017;207(1):215–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. De Tomasi L, et al. Mutations in GREB1L cause bilateral kidney agenesis in humans and mice. Am J Hum Genet. 2017;101(5):803–14.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Jacquinet A, et al. GREB1L variants in familial and sporadic hereditary urogenital adysplasia and Mayer-Rokitansky-Kuster-Hauser syndrome. Clin Genet. 2020;98(2):126–37.

    Article  CAS  PubMed  Google Scholar 

  67. Groopman EE, et al. Diagnostic utility of exome sequencing for kidney disease. N Engl J Med. 2019;380(2):142–51.

    Article  CAS  PubMed  Google Scholar 

  68. Connaughton DM, et al. Monogenic causes of chronic kidney disease in adults. Kidney Int. 2019;95(4):914–28.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lei TY, et al. Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract. Nephrol Dial Transplant. 2017;32(10):1665–75.

    Article  CAS  PubMed  Google Scholar 

  70. Nicolaou N, et al. Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT. Kidney Int. 2016;89(2):476–86.

    Article  CAS  PubMed  Google Scholar 

  71. Ahram DF, Aggarwal VS, Sanna-Cherchi S. Phenocopies, phenotypic expansion, and coincidental diagnoses: time to abandon targeted gene panels? Am J Kidney Dis. 2020;76(4):451–3.

    Article  PubMed  Google Scholar 

  72. Golzio C, Katsanis N. Genetic architecture of reciprocal CNVs. Curr Opin Genet Dev. 2013;23(3):240–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sanna-Cherchi S, et al. Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 2012;91(6):987–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Westland R, et al. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney. Kidney Int. 2015;88(6):1402–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Verbitsky M, et al. The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet. 2019;51(1):117–27.

    Article  CAS  PubMed  Google Scholar 

  76. Lopez-Rivera E, et al. Genetic drivers of kidney defects in the DiGeorge syndrome. N Engl J Med. 2017;376(8):742–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Golzio C, et al. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature. 2012;485(7398):363–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Haller M, et al. 16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A. 2018;115(8):E1849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Verbitsky M, et al. Genomic imbalances in pediatric patients with chronic kidney disease. J Clin Invest. 2015;125(5):2171–8.

    Article  PubMed  PubMed Central  Google Scholar 

  80. South ST, et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 2013;15(11):901–9.

    Article  CAS  PubMed  Google Scholar 

  81. Khera AV, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Oda T, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16(3):235–42.

    Article  CAS  PubMed  Google Scholar 

  83. Wilkie AO, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995;9(2):165–72.

    Article  CAS  PubMed  Google Scholar 

  84. Enklaar T, Zabel BU, Prawitt D. Beckwith-Wiedemann syndrome: multiple molecular mechanisms. Expert Rev Mol Med. 2006;8(17):1–19.

    Article  PubMed  Google Scholar 

  85. Kochhar A, et al. Branchio-oto-renal syndrome. Am J Med Genet A. 2007;143A(14):1671–8.

    Article  CAS  PubMed  Google Scholar 

  86. Abdelhak S, et al. Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Hum Mol Genet. 1997;6(13):2247–55.

    Article  CAS  PubMed  Google Scholar 

  87. Heidet L, et al. Targeted exome sequencing identifies PBX1 as involved in monogenic congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol. 2017;28(10):2901–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Houston CS, et al. The campomelic syndrome: review, report of 17 cases, and follow-up on the currently 17-year-old boy first reported by Maroteaux et al in 1971. Am J Med Genet. 1983;15(1):3–28.

    Article  CAS  PubMed  Google Scholar 

  89. Wagner T, et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994;79(6):1111–20.

    Article  CAS  PubMed  Google Scholar 

  90. Kujat A, et al. Renal malformations in deletion 22q11.2 patients. Am J Med Genet A. 2006;140(14):1601–2.

    Article  PubMed  Google Scholar 

  91. McGregor L, et al. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet. 2003;34(2):203–8.

    Article  CAS  PubMed  Google Scholar 

  92. Muroya K, et al. GATA3 abnormalities and the phenotypic spectrum of HDR syndrome. J Med Genet. 2001;38(6):374–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Van Esch H, et al. GATA3 haplo-insufficiency causes human HDR syndrome. Nature. 2000;406(6794):419–22.

    Article  PubMed  Google Scholar 

  94. Beales PL, et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet. 2007;39(6):727–9.

    Article  CAS  PubMed  Google Scholar 

  95. Duke V, et al. Proteinuria, hypertension and chronic renal failure in X-linked Kallmann’s syndrome, a defined genetic cause of solitary functioning kidney. Nephrol Dial Transplant. 1998;13(8):1998–2003.

    Article  CAS  PubMed  Google Scholar 

  96. Franco B, et al. A gene deleted in Kallmann’s syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature. 1991;353(6344):529–36.

    Article  CAS  PubMed  Google Scholar 

  97. Bamshad M, et al. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Genet. 1997;16(3):311–5.

    Article  CAS  PubMed  Google Scholar 

  98. Pittock ST, Babovic-Vuksanovic D, Lteif A. Mayer-Rokitansky-Kuster-Hauser anomaly and its associated malformations. Am J Med Genet A. 2005;135(3):314–6.

    Article  PubMed  Google Scholar 

  99. Sakaki-Yumoto M, et al. The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development. Development. 2006;133(15):3005–13.

    Article  CAS  PubMed  Google Scholar 

  100. Kang S, et al. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet. 1997;15(3):266–8.

    Article  CAS  PubMed  Google Scholar 

  101. Bohn S, et al. Distinct molecular and morphogenetic properties of mutations in the human HNF1beta gene that lead to defective kidney development. J Am Soc Nephrol. 2003;14(8):2033–41.

    Article  CAS  PubMed  Google Scholar 

  102. Gribouval O, et al. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. Hum Mutat. 2012;33(2):316–26.

    Article  CAS  PubMed  Google Scholar 

  103. Kanjilal D, et al. New dysmorphic features in Rubinstein-Taybi syndrome. J Med Genet. 1992;29(9):669–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Pilia G, et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12(3):241–7.

    Article  CAS  PubMed  Google Scholar 

  105. Tint GS, et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994;330(2):107–13.

    Article  CAS  PubMed  Google Scholar 

  106. Kohlhase J, et al. Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet. 1998;18(1):81–3.

    Article  CAS  PubMed  Google Scholar 

  107. Preuss N, et al. PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease. Pediatr Res. 2002;51(6):706–14.

    Article  CAS  PubMed  Google Scholar 

  108. Fujimura S, et al. Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol. 2010;21(5):803–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Guo Q, et al. Adam10 mediates the choice between principal cells and intercalated cells in the kidney. J Am Soc Nephrol. 2015;26(1):149–59.

    Article  CAS  PubMed  Google Scholar 

  110. Zhao H, et al. Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol. 2004;276(2):403–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Weksberg R, Shuman C, Smith AC. Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet. 2005;137C(1):12–23.

    Article  PubMed  Google Scholar 

  112. Fraser FC, et al. Genetic aspects of the BOR syndrome – branchial fistulas, ear pits, hearing loss, and renal anomalies. Am J Med Genet. 1978;2(3):241–52.

    Article  CAS  PubMed  Google Scholar 

  113. O’Brien LL, et al. Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies. PLoS Genet. 2018;14(1):e1007181.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Xu J, et al. Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis. Dev Cell. 2014;31(4):434–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Self M, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25(21):5214–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Hwang DY, et al. Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. Kidney Int. 2014;85(6):1429–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Chitayat D, et al. Branchio-oto-renal syndrome: further delineation of an underdiagnosed syndrome. Am J Med Genet. 1992;43(6):970–5.

    Article  CAS  PubMed  Google Scholar 

  118. Reginensi A, et al. SOX9 controls epithelial branching by activating RET effector genes during kidney development. Hum Mol Genet. 2011;20(6):1143–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Schnabel CA, Godin RE, Cleary ML. Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney. Dev Biol. 2003;254(2):262–76.

    Article  CAS  PubMed  Google Scholar 

  120. Pavlakis E, Chiotaki R, Chalepakis G. The role of Fras1/Frem proteins in the structure and function of basement membrane. Int J Biochem Cell Biol. 2011;43(4):487–95.

    Article  CAS  PubMed  Google Scholar 

  121. Kohl S, et al. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol. 2014;25(9):1917–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Pitera JE, Scambler PJ, Woolf AS. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Hum Mol Genet. 2008;17(24):3953–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Pitera JE, et al. Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. J Am Soc Nephrol. 2012;23(11):1790–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Grote D, et al. Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction. PLoS Genet. 2008;4(12):e1000316.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Kirk JM, et al. Unilateral renal aplasia in X-linked Kallmann’s syndrome. Clin Genet. 1994;46(3):260–2.

    Article  CAS  PubMed  Google Scholar 

  126. Reidy KJ, et al. Excess podocyte semaphorin-3A leads to glomerular disease involving plexinA1-nephrin interaction. Am J Pathol. 2013;183(4):1156–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Hanchate NK, et al. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet. 2012;8(8):e1002896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Barry DM, et al. Molecular determinants of nephron vascular specialization in the kidney. Nat Commun. 2019;10(1):5705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. McPherson E, Cold C. Severe Pallister-Hall syndrome with persistent urogenital sinus, renal agenesis, imperforate anus, bilateral hypothalamic hamartomas, and severe skeletal anomalies. Am J Med Genet A. 2013;161A(10):2666–9.

    PubMed  Google Scholar 

  130. Blake J, et al. Urogenital development in Pallister-Hall syndrome is disrupted in a cell-lineage-specific manner by constitutive expression of GLI3 repressor. Hum Mol Genet. 2016;25(3):437–47.

    Article  CAS  PubMed  Google Scholar 

  131. Weaver RG, et al. Optic nerve coloboma associated with renal disease. Am J Med Genet. 1988;29(3):597–605.

    Article  CAS  PubMed  Google Scholar 

  132. Bouchard M, et al. Nephric lineage specification by Pax2 and Pax8. Genes Dev. 2002;16(22):2958–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Murawski IJ, et al. Vesico-ureteric reflux and urinary tract development in the Pax2 1Neu+/− mouse. Am J Physiol Renal Physiol. 2007;293(5):F1736–45.

    Article  CAS  PubMed  Google Scholar 

  134. Patel SR, et al. The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev Cell. 2007;13(4):580–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Brophy PD, et al. Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene. Development. 2001;128(23):4747–56.

    Article  CAS  PubMed  Google Scholar 

  136. Heidet L, et al. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol. 2010;5(6):1079–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Ulinski T, et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol. 2006;17(2):497–503.

    Article  CAS  PubMed  Google Scholar 

  138. Desgrange A, et al. HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis. Development. 2017;144(24):4704–19.

    CAS  PubMed  Google Scholar 

  139. Hiesberger T, et al. Mutation of hepatocyte nuclear factor-1beta inhibits Pkhd1 gene expression and produces renal cysts in mice. J Clin Invest. 2004;113(6):814–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Gribouval O, et al. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005;37(9):964–8.

    Article  CAS  PubMed  Google Scholar 

  141. Uematsu M, et al. A further case of renal tubular dysgenesis surviving the neonatal period. Eur J Pediatr. 2009;168(2):207–9.

    Article  PubMed  Google Scholar 

  142. Lacoste M, et al. Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: role of the Renin-Angiotensin system. J Am Soc Nephrol. 2006;17(8):2253–63.

    Article  CAS  PubMed  Google Scholar 

  143. Nishimura H, et al. Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell. 1999;3(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  144. Hahn H, et al. Implication of genetic variations in congenital obstructive nephropathy. Pediatr Nephrol. 2005;20(11):1541–4.

    Article  PubMed  Google Scholar 

  145. Roelfsema JH, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005;76(4):572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Gomez RA, et al. CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am J Physiol Heart Circ Physiol. 2009;296(5):H1255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Behmel A, Plochl E, Rosenkranz W. A new X-linked dysplasia gigantism syndrome: identical with the Simpson dysplasia syndrome? Hum Genet. 1984;67(4):409–13.

    Article  CAS  PubMed  Google Scholar 

  148. Cano-Gauci DF, et al. Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson-Golabi-Behmel syndrome. J Cell Biol. 1999;146(1):255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Hartwig S, et al. Glypican-3 modulates inhibitory Bmp2-Smad signaling to control renal development in vivo. Mech Dev. 2005;122(7–8):928–38.

    Article  CAS  PubMed  Google Scholar 

  150. Gou-Fabregas M, et al. 7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome. Sci Rep. 2016;6:28534.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Powell CM, Michaelis RC. Townes-Brocks syndrome. J Med Genet. 1999;36(2):89–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Nishinakamura R, Takasato M. Essential roles of Sall1 in kidney development. Kidney Int. 2005;68(5):1948–50.

    Article  CAS  PubMed  Google Scholar 

  153. Kanda S, et al. Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. J Am Soc Nephrol. 2014;25(11):2584–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Altug-Teber O, et al. Specific transcriptional changes in human fetuses with autosomal trisomies. Cytogenet Genome Res. 2007;119(3–4):171–84.

    Article  CAS  PubMed  Google Scholar 

  155. Stoll C, et al. Associated congenital anomalies among cases with Down syndrome. Eur J Med Genet. 2015;58(12):674–80.

    Article  PubMed  Google Scholar 

  156. Mercer ES, et al. Urological manifestations of Down syndrome. J Urol. 2004;171(3):1250–3.

    Article  PubMed  Google Scholar 

  157. Pont SJ, et al. Congenital malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet A. 2006;140(16):1749–56.

    Article  PubMed  Google Scholar 

  158. Groen In’t Woud S, et al. Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: A case-control study. Birth Defects Res A Clin Mol Teratol. 2016;106(7):596–603.

    Google Scholar 

  159. Dart AB, et al. Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child. Am J Kidney Dis. 2015;65(5):684–91.

    Article  PubMed  Google Scholar 

  160. Amri K, et al. Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies. Diabetes. 1999;48(11):2240–5.

    Article  CAS  PubMed  Google Scholar 

  161. Gjerde A, et al. Intrauterine growth restriction and risk of diverse forms of kidney disease during the first 50 years of life. Clin J Am Soc Nephrol. 2020;15(10):1413–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Cooper WO, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354(23):2443–51.

    Article  CAS  PubMed  Google Scholar 

  163. Martinovic J, et al. Fetal toxic effects and angiotensin-II-receptor antagonists. Lancet. 2001;358(9277):241–2.

    Article  CAS  PubMed  Google Scholar 

  164. Havers W, et al. Anomalies of the kidneys and genitourinary tract in alcoholic embryopathy. J Urol. 1980;124(1):108–10.

    Article  CAS  PubMed  Google Scholar 

  165. Das SK, et al. Maternal alcohol consumption during pregnancy and its association with offspring renal function at 30 years: observation from a birth cohort study. Nephrology (Carlton). 2019;24(1):21–7.

    Article  CAS  Google Scholar 

  166. Rosenstein BJ, Wheeler JS, Heid PL. Congenital renal abnormalities in infants with in utero cocaine exposure. J Urol. 1990;144(1):110–2.

    Article  CAS  PubMed  Google Scholar 

  167. Dickinson H, et al. Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R453–61.

    Article  CAS  PubMed  Google Scholar 

  168. Singh RR, et al. Effects of dexamethasone exposure on rat metanephric development: in vitro and in vivo studies. Am J Physiol Renal Physiol. 2007;293(2):F548–54.

    Article  CAS  PubMed  Google Scholar 

  169. Brennan KA, et al. Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring. Am J Physiol Regul Integr Comp Physiol. 2008;295(1):R197–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Welham SJ, et al. Maternal diet programs embryonic kidney gene expression. Physiol Genomics. 2005;22(1):48–56.

    Article  CAS  PubMed  Google Scholar 

  171. McBride WG. Thalidomide embryopathy. Teratology. 1977;16(1):79–82.

    Article  CAS  PubMed  Google Scholar 

  172. Smithells RW, Newman CG. Recognition of thalidomide defects. J Med Genet. 1992;29(10):716–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Schreuder MF, et al. Glomerular number and function are influenced by spontaneous and induced low birth weight in rats. J Am Soc Nephrol. 2005;16(10):2913–9.

    Article  PubMed  Google Scholar 

  174. Huot C, et al. Congenital malformations associated with maternal use of valproic acid. Can J Neurol Sci. 1987;14(3):290–3.

    Article  CAS  PubMed  Google Scholar 

  175. Lelievre-Pegorier M, et al. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998;54(5):1455–62.

    Article  CAS  PubMed  Google Scholar 

  176. Wilson JG, Roth CB, Warkany J. An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat. 1953;92(2):189–217.

    Article  CAS  PubMed  Google Scholar 

  177. Wlodek ME, et al. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007;18(6):1688–96.

    Article  CAS  PubMed  Google Scholar 

  178. Woods LL, et al. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001;49(4):460–7.

    Article  CAS  PubMed  Google Scholar 

  179. Tufro-McReddie A, et al. Angiotensin II regulates nephrogenesis and renal vascular development. Am J Phys. 1995;269(1 Pt 2):F110–5.

    CAS  Google Scholar 

  180. Iosipiv IV, Schroeder M. A role for angiotensin II AT1 receptors in ureteric bud cell branching. Am J Physiol Renal Physiol. 2003;285(2):F199–207.

    Article  CAS  PubMed  Google Scholar 

  181. Makrakis J, Zimanyi MA, Black MJ. Retinoic acid enhances nephron endowment in rats exposed to maternal protein restriction. Pediatr Nephrol. 2007;22(11):1861–7.

    Article  PubMed  Google Scholar 

  182. Mendelsohn C, et al. Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development. 1994;120(10):2749–71.

    Article  CAS  PubMed  Google Scholar 

  183. Hernandez-Diaz S, et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med. 2000;343(22):1608–14.

    Article  CAS  PubMed  Google Scholar 

  184. Zachman RD, Grummer MA. The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome. Alcohol Clin Exp Res. 1998;22(7):1544–56.

    Article  CAS  PubMed  Google Scholar 

  185. Ichikawa. Kidney Int 61(3):889–98, 2002.

    Google Scholar 

  186. Westland et al. Clin J Am Soc Nephrol, 2020.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Division of Nephrology, McGill University Health Centre, Montreal, QC, Canada

    Paul Goodyer & Indra R. Gupta

  2. Department of Pediatric Nephrology, Amsterdam UMC – Emma Children’s Hospital, Amsterdam, The Netherlands

    Rik Westland

  3. Department of Pediatrics, Tulane University, New Orleans, LA, USA

    Ihor Yosypiv

Authors
  1. Paul Goodyer
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  2. Indra R. Gupta
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  3. Rik Westland
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  4. Ihor Yosypiv
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Corresponding author

Correspondence to Indra R. Gupta .

Editor information

Editors and Affiliations

  1. Division of Nephrology, Department of Pediatric Specialties, Bambino Gesù Children’s Hospital – IRCCS, Rome, Italy

    Francesco Emma

  2. Division of Nephrology and Hypertension, The Heart Institute, Cincinnati Children’s Hospital Medical Center, College of Medicine, Cincinnati, OH, USA

    Stuart L. Goldstein

  3. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Arvind Bagga

  4. Division of Pediatric Nephrology, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Carlton M. Bates

  5. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, NHS Foundation Trust and University College London Institute of Child Health, London, UK

    Rukshana Shroff

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Goodyer, P., Gupta, I.R., Westland, R., Yosypiv, I. (2022). Congenital Anomalies of the Kidneys. In: Emma, F., Goldstein, S.L., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Cham. https://doi.org/10.1007/978-3-030-52719-8_86

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