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The Urinary System

  • Jelena MartinovicEmail author

Abstract

The development of the kidney and the urinary tract is directed by a highly complex cellular dialog between the ureteric bud and metanephric mesenchyme. Developmental defects are the result of disruptions in this reciprocal signaling. The complexity of signaling pathways in nephrogenesis explains the locus heterogeneity of congenital anomalies of the kidney and urinary tract (CAKUT). However, under this single label acronym lie different phenotypes, which present an incomplete penetrance and variable clinical presentation during the fetal period, making uniform and extended data collections difficult and introducing potential selection bias. There is not only clinical but also genetic support to the use of CAKUT, because it is well known that mutations in a single gene have pleiotropic effects on the development of the urogenital tract. The precise analysis of phenotypes with the establishment of genotype/phenotype correlations remains a gold standard for taking full advantage from genomics. The standard definitions of patients’ phenotypes are mandatory for the data exchange: semantic standards ensure that the terms used consistently correlate with described patient characteristics.

Keywords

Kidney Renal development Renal disease Congenital anomalies of the kidney and urinary tract CAKUT Polycystic kidney diseases PKD Renal histology Renal genetics Teratogens Hereditary nephropathies 

References

  1. 1.
    Pope 4th JC, Brock 3rd JW, Adams MC, Stephens FD, Ichikawa I. How they begin and how they end: classic and new theories for the development and deterioration of congenital anomalies of the kidney and urinary tract. CAKUT. J Am Soc Nephrol. 1999;10:2018–28.PubMedGoogle Scholar
  2. 2.
    Eccles MR, Schimmenti LA. Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. Clin Genet. 1999;56:1–9.PubMedGoogle Scholar
  3. 3.
    Robinson PN. Deep phenotyping for precision medicine. Hum Mut. 2012;33:777–80.PubMedGoogle Scholar
  4. 4.
    Lipschutz JH. Molecular development of the kidney: a review of the results of gene disruption studies. Am J Kidney Dis. 1998;31:383–97.PubMedGoogle Scholar
  5. 5.
    Vize P, Woolf A, Bard J. The kidney: from normal development to congenital disease. New York: Academic; 2003.Google Scholar
  6. 6.
    Saxen L, Sariola H. Early organogenesis of the kidney. Pediatr Nephrol. 1987;1:385–92.PubMedGoogle Scholar
  7. 7.
    Cebrian C, Asai N, D’Agati V, Costantini F. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment. Cell Rep. 2014;7:127–37.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Hartman HA, Lai HL, Patterson LT. Cessation of renal morphogenesis in mice. Dev Biol. 2007;310:379–87.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Rumballe BA, Georgas KM, Combes AN, Ju AL, Gilbert T, Little MH. Nephron formation adopts a novel spatial topology at cessation of nephrogenesis. Dev Biol. 2011;360:110–22.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Brunskill EW, Lai HL, Jamison DC, Potter SS, Patterson LT. Microarrays and RNA-Seq identify molecular mechanisms driving the end of nephron production. BMC Dev Biol. 2011;11:15.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Cullen-McEwen LA, Caruana G, Bertram JF. The where, what and why of the developing renal stroma. Nephron Exp Nephrol. 2005;99:E1–8.PubMedGoogle Scholar
  12. 12.
    Dorovini-Zis K, Dolman CL. Gestational development of brain. Arch Pathol Lab Med. 1977;101:192–5.PubMedGoogle Scholar
  13. 13.
    Patterson LT, Pembaur M, Potter SS. Hoxa11 et Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Development. 2001;128:2153–61.PubMedGoogle Scholar
  14. 14.
    Wellik DM, Hawkes PJ, Capecchi MR. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev. 2002;16:1423–32.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier D. WT-1 is required for early kidney development. Cell. 1993;74:679–91.Google Scholar
  16. 16.
    Moore MW, Klein RD, Fariñas I, Sauer H, Armanini M, Phillips H, et al. Renal and neuronal abnormalities in mice lacking GDNF. Nature. 1996;382:76–9.PubMedGoogle Scholar
  17. 17.
    Schuchardt A, D’Agati V, Pachnis V, Constantini F. Renal agenesis and hypodysplasia in ret–k– mutant mice result from defects in ureteric bud development. Development. 1996;122:1919–29.Google Scholar
  18. 18.
    Davies JA, Lyon M, Gallagher J, Garrod DR. Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development. Development. 1995;121:1507–17.PubMedGoogle Scholar
  19. 19.
    Perantoni AO, Dove LF, Karavanova I. Basic fibroblast growth factor can mediate the early inductive events in renal development. Proc Natl Acad Sci U S A. 1995;92:4696–700.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Dudley AT, Lyons KM, Robertson EJ. A requirement for bone morphogenesis protein-7 during development of the mammalian kidney and eye. Genes Dev. 1995;9:2795–807.PubMedGoogle Scholar
  21. 21.
    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;17:3953–64.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Barasch J, Yang J, Ware CB, Taga T, Yoshida K, Erdjument-Bromage H, et al. Mesenchymal to epithelial conversion in rat metanephros is induced by LIF. Cell. 1999;99:377–86.PubMedGoogle Scholar
  23. 23.
    Itäranta P, Lin Y, Peräsaari J, Roël G, Destrée O, Vainio S. Wnt-6 is expressed in ureter bud and induces kidney tubule development in vitro. Genesis. 2002;32:259–68.PubMedGoogle Scholar
  24. 24.
    Kispert A, Vainio S, McMahon AP. Wnt-4 is a mesenchymal signal for epithelial transformation of metanephric mesenchyme in the developing kidney. Development. 1998;125:4225–34.PubMedGoogle Scholar
  25. 25.
    Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, et al. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci U S A. 1996;93:1524–8.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Sainio K, Suvanto P, Davies J, Wartiovaara J, Wartiovaara K, Saarma M, et al. Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development. 1997;124:4077–87.PubMedGoogle Scholar
  27. 27.
    Nakamura T, Okuda S, Miller D, Ruoslahti E, Border W. Transforming growth factor β (TGF- β) regulates production of extracellular matrix (ECM) components by glomerular epithelial cells. Kidney Int. 1990;37:221.Google Scholar
  28. 28.
    Miyazaki YK, Oshima K, Fogo A, Hogan BL, Ichikawa. Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J Clin Invest. 2000;105:863–73.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Lin Y, Zhang S, Rehn M, Itäranta P, Tuukkanen J, Heljäsvaara R, et al. Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactant protein C. Development. 2001;128:1573–85.PubMedGoogle Scholar
  30. 30.
    Hatini V, Huh SO, Herzlinger D, Soares VC, Lai E. Essential role of stromal morphogenesis in kidney morphogenesis revealed by targeted disruption of winged helix transcription factor, BF-2. Genes Dev. 1996;10:1467–78.PubMedGoogle Scholar
  31. 31.
    Batourina E, Choi C, Paragas N, Bello N, Hensle T, Costantini FD, et al. Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat Genet. 2002;32:109–15.PubMedGoogle Scholar
  32. 32.
    Qiao J, Uzzo R, Obara-Ishihara T, Degenstein L, Fuchs E, Herzlinger D. FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development. 1999;126:547–54.PubMedGoogle Scholar
  33. 33.
    Little MH, Bertram JF. Is there such a thing as a renal stem cell? J Am Soc Nephrol. 2009;20:2112–7.PubMedGoogle Scholar
  34. 34.
    Boyle S, Misfeldt A, Chandler KJ, Deal KK, Southard-Smith EM, Mortlock DP, et al. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Dev Biol. 2008;313:234–45.PubMedGoogle Scholar
  35. 35.
    Self M, Lagutin OV, Bowling B, Hendrix J, Cai Y, Dressler GR, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214–28.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008;3:169–81.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Barak H, Huh SH, Chen S, Jeanpierre C, Martinovic J, Parisot M, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012;22:1191–207.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epidemiology of chronic kidney disease in children. Pediatr Nephrol. 2012;27:363–73.PubMedGoogle Scholar
  39. 39.
    Ichikawa I, Kuwayama F, Pope 4th JC, Stephens FD, Miyazaki Y. Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT. Kidney Int. 2002;61:889–98.PubMedGoogle Scholar
  40. 40.
    Kerecuk L, Sajoo A, McGregor L, Berg J, Haq MR, Sebire NJ, et al. Autosomal dominant inheritance of non-syndromic renal hypoplasia and dysplasia: dramatic variation in clinical severity in a single kindred. Nephrol Dial Transplant. 2007;22:259–63.PubMedGoogle Scholar
  41. 41.
    Schwaderer AL, Bates CM, McHugh KM, McBride KL. Renal anomalies in family members of infants with bilateral renal agenesis/adysplasia. Pediatr Nephrol. 2007;22:52–6.PubMedGoogle Scholar
  42. 42.
    Ashraf S, Hoskins BE, Chaib H, Hoefele J, Pasch A, Saisawat P, et al. Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24. Nephrol Dial Transplant. 2010;25:1496–501.PubMedGoogle Scholar
  43. 43.
    Renkema KY, Winyard PJ, Skovorodkin IN, Levtchenko E, Hindryckx A, Jeanpierre C, et al. Novel perspectives for investigating congenital anomalies of the kidney and urinary tract (CAKUT). Nephrol Dial Transplant. 2011;26:3843–51.PubMedGoogle Scholar
  44. 44.
    Daïkha-Dahmane F, Dommergues M, Muller F, Narcy F, Lacoste M, Beziau A, et al. Development of human fetal kidney in obstructive uropathy: correlations with ultrasonography and urine biochemistry. Kidney Int. 1997;52:21–32.PubMedGoogle Scholar
  45. 45.
    Cordell HJ, Darlay R, Charoen P, Stewart A, Gullett AM, Lambert HJ, et al. Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux. J Am Soc Nephrol. 2010;21:113–23.PubMedPubMedCentralGoogle Scholar
  46. 46.
    van Eerde AM, Meutgeert MH, de Jong TP, Giltay JC. Vesico-ureteral reflux in children with prenatally detected hydronephrosis: a systematic review. Ultrasound Obstet Gynecol. 2007;29:463–9.PubMedGoogle Scholar
  47. 47.
    Sanna-Cherchi S, Sampogna RV, Papeta N, Burgess KE, Nees SN, Perry BJ, et al. Mutations in DSTYK and dominant urinary tract malformations. N Engl J Med. 2013;369:621–9.PubMedGoogle Scholar
  48. 48.
    Jeanpierre C, Macé G, Parisot M, Morinière V, Pawtowsky A, Benabou M, et al. RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet. 2011;48:497–504.PubMedGoogle Scholar
  49. 49.
    Saisawat P, Tasic V, Vega-Warner V, Kehinde EO, Günther B, Airik R, et al. Identification of two novel CAKUT-causing genes by massively parallel exon resequencing of candidate genes in patients with unilateral renal agenesis. Kidney Int. 2012;81:196–200.PubMedGoogle Scholar
  50. 50.
    Humbert C, Silbermann F, Morar B, Parisot M, Zarhrate M, Masson C, et al. Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans. Am J Hum Genet. 2014;94:288–94.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Hwang DY, Dworschak GC, Kohl S, Saisawat P, Vivante A, Hilger AC, et al. Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. Kidney Int. 2013;85:1429–33.Google Scholar
  52. 52.
    Bates CM. Role of fibroblast growth factor receptor signaling in kidney development. Am J Physiol Renal Physiol. 2011;301:F245–51.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Martinovic-Bouriel J, Benachi A, Bonnière M, Brahimi N, Esculpavit C, Morichon N, et al. PAX2 mutations in fetal renal hypodysplasia. Am J Med Genet A. 2010;152A:830–5.PubMedGoogle Scholar
  54. 54.
    Li M, Squire JA, Weksberg R. Molecular genetics of Wiedemann-Beckwith syndrome. Am J Med Genet. 1998;79:253–9.PubMedGoogle Scholar
  55. 55.
    Goldman M, Smith A, Shuman C, Caluseriu O, Wei C, Steele L, et al. Renal abnormalities in beckwith-wiedemann syndrome are associated with 11p15.5 uniparental disomy. J Am Soc Nephrol. 2002;13:2077–84.PubMedGoogle Scholar
  56. 56.
    Henneveld HT, van Lingen RA, Hamel BC, Stolte-Dijkstra I, van Essen AJ. Perlman syndrome: four additional cases and review. Am J Med Genet. 1999;86:439–46.PubMedGoogle Scholar
  57. 57.
    Astuti D, Morris MR, Cooper WN, Staals RH, Wake NC, Fews GA, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet. 2012;44:277–84.PubMedGoogle Scholar
  58. 58.
    Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12:241–7.PubMedGoogle Scholar
  59. 59.
    Li M, Shuman C, Fei YL, Cutiongco E, Bender HA, Stevens C, et al. GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome. Am J Med Genet. 2001;102:161–8.PubMedGoogle Scholar
  60. 60.
    Waterson J, Stockley TL, Segal S, Golabi M. Novel duplication in glypican-4 as an apparent cause of Simpson-Golabi-Behmel syndrome. Am J Med Genet. 2010;152A:3179–81.PubMedGoogle Scholar
  61. 61.
    Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006;43:306–14.PubMedGoogle Scholar
  62. 62.
    Alazami AM, Shaheen R, Alzahrani F, Snape K, Saggar A, Brinkmann B, et al. FREM1 mutations cause bifid nose, renal agenesis, and anorectal malformations syndrome. Am J Hum Genet. 2009;85:414–8.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Bingham C, Bulman MP, Ellard S, Allen LI, Lipkin GW, Hoff WG, et al. Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet. 2001;68:219–24.PubMedGoogle Scholar
  64. 64.
    Haumaitre C, Fabre M, Cormier S, Baumann C, Delezoide AL, Cereghini S. Severe pancreas hypoplasia and multicystic renal dysplasia in two human fetuses carrying novel HNF1beta/MODY5 mutations. Hum Mol Genet. 2006;15:2363–75.PubMedGoogle Scholar
  65. 65.
    Edghill EL, Bingham C, Slingerland AS, Minton JA, Noordam C, Ellard S, et al. Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development. Diabet Med. 2006;23:1301–6.PubMedGoogle Scholar
  66. 66.
    Decramer S, Parant O, Beaufils S, Clauin S, Guillou C, Kessler S, et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol. 2007;18:923–33.PubMedGoogle Scholar
  67. 67.
    Madariaga L, Morinière V, Jeanpierre C, Bouvier R, Loget P, Martinovic J, et al. Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin J Am Soc Nephrol. 2013;8:1179–87.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Harris PC, Rossetti S. Molecular genetics of autosomal recessive polycystic kidney disease. Mol Genet Metab. 2004;81:75–85.PubMedGoogle Scholar
  69. 69.
    Al-Bhalal L, Akhtar M. Molecular basis of autosomal recessive polycystic kidney disease (ARPKD). Adv Anat Pathol. 2008;15:54–8.PubMedGoogle Scholar
  70. 70.
    Denamur E, Delezoide AL, Alberti C, Bourillon A, Gubler MC, Bouvier R, et al. Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease. Kidney Int. 2010;77:350–8.PubMedGoogle Scholar
  71. 71.
    Gabow PA. Autosomal dominant polycystic kidney disease. N Engl J Med. 1993;329:332–42.PubMedGoogle Scholar
  72. 72.
    Peters DJ, Sandkuijl LA. Genetic heterogeneity of polycystic kidney disease in Europe. Contrib Nephrol. 1992;97:128–39.PubMedGoogle Scholar
  73. 73.
    Demetriou K, Tziakouri C, Anninou K, Eleftheriou A, Koptides M, Nicolaou A, et al. Autosomal dominant polycystic kidney disease-type 2. Ultrasound, genetic and clinical correlations. Nephrol Dial Transplant. 2000;15:205–11.PubMedGoogle Scholar
  74. 74.
    Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet. 1999;353:103–7.PubMedGoogle Scholar
  75. 75.
    Magistroni R, He N, Wang K, Andrew R, Johnson A, Gabow P, et al. Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2003;14:1164–74.PubMedGoogle Scholar
  76. 76.
    Fain PR, McFann KK, Taylor MR, Tison M, Johnson AM, Reed B, et al. Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int. 2005;67:1256–67.PubMedGoogle Scholar
  77. 77.
    Garcia-Gonzalez MA, Jones JG, Allen SK, Palatucci CM, Batish SD, Seltzer WK, et al. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol Genet Metab. 2007;92:160–7.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Rossetti S, Harris PC. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol. 2007;18:1374–80.PubMedGoogle Scholar
  79. 79.
    Kyttälä M, Tallila J, Salonen R, Kopra O, Kohlschmidt N, Paavola-Sakki P, et al. MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat Genet. 2006;38:155–7.PubMedGoogle Scholar
  80. 80.
    Iannicelli M, Brancati F, Mougou-Zerelli S, Mazzotta A, Thomas S, Elkhartoufi N, et al. Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies. Hum Mutat. 2010;31:E1319–31.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Baala L, Audollent S, Martinovic J, Ozilou C, Babron MC, Sivanandamoorthy S, et al. Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. Am J Hum Genet. 2007;81:170–9.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, et al. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007;39:875–81.PubMedGoogle Scholar
  83. 83.
    Shaheen R, Faqeih E, Seidahmed MZ, Sunker A, Alali FE, AlQahtani K, et al. A TCTN2 mutation defines a novel Meckel Gruber syndrome locus. Hum Mutat. 2011;32:573–8.PubMedGoogle Scholar
  84. 84.
    Hopp K, Heyer CM, Hommerding CJ, Henke SA, Sundsbak JL, Patel S, et al. B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis. Hum Mol Genet. 2011;20:2524–34.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Shaheen R, Shamseldin HE, Loucks CM, Seidahmed MZ, Ansari S, Ibrahim Khalil M, et al. Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans. Am J Hum Genet. 2014;94:73–9.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Khaddour R, Smith U, Baala L, Martinovic J, Clavering D, Shaffiq R, et al. Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Hum Mutat. 2007;28:523–4.PubMedGoogle Scholar
  87. 87.
    Romani M, Micalizzi A, Kraoua I, Dotti MT, Cavallin M, Sztriha L, et al. Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome. Orphanet J Rare Dis. 2014;9:72.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011;145:513–28.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Karmous-Benailly H, Martinovic J, Gubler MC, Sirot Y, Clecj L, Ozilou C, et al. Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome. Am J Hum Genet. 2005;76:493–504.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Badano JL, Kim JC, Hoskins BE, Lewis RA, Ansley SJ, Cutler DJ, et al. Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus. Hum Mol Genet. 2003;12:1651–9.PubMedGoogle Scholar
  91. 91.
    Kim SK, Shindo A, Park TJ, Oh EC, Ghosh S, Gray RS, et al. Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science. 2010;329:1337–40.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Schaefer E, Zaloszyc A, Lauer J, Durand M, Stutzmann F, Perdomo-Trujillo Y, et al. Mutations in SDCCAG8/NPHP10 cause Bardet-Biedl Syndrome and are associated with penetrant renal disease and absent polydactyly. Mol Syndromol. 2011;1:273–81.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Marion V, Stutzmann F, Gérard M, De Melo C, Schaefer E, Claussmann A, et al. Exome sequencing identifies mutations in LZTFL1, a BBSome and smoothened trafficking regulator, in a family with Bardet-Biedl syndrome with situs inversus and insertional polydactyly. J Med Genet. 2012;49:317–21.PubMedGoogle Scholar
  94. 94.
    Scheidecker S, Etard C, Pierce NW, Geoffroy V, Schaefer E, Muller J, et al. Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J Med Genet. 2014;51:132–6.PubMedGoogle Scholar
  95. 95.
    Aldahmesh MA, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, et al. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum Mol Genet. 2014;15:3307–15.Google Scholar
  96. 96.
    Ivemark BI, Oldfelt V, Zetterstrom R. Familial dysplasia of kidneys, liver and pancreas: probably a genetically determined syndrome. Acta Paediatr. 1959;48:1–11.PubMedGoogle Scholar
  97. 97.
    Larson RS, Rudloff MA, Liapis H, Manes JL, Davila R, Kissane J. The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations. Pediatr Nephrol. 1995;9:594–8.PubMedGoogle Scholar
  98. 98.
    Bergmann C, Fliegauf M, Brüchle NO, Frank V, Olbrich H, Kirschner J, et al. Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am J Hum Genet. 2008;82:959–70.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Moalem S, Keating S, Shannon P, Thompson M, Millar K, Nykamp K, et al. Broadening the ciliopathy spectrum: motile cilia dyskinesia, and nephronophthisis associated with a previously unreported homozygous mutation in the INVS/NPHP2 gene. Am J Med Genet A. 2013;161A:1792–6.PubMedGoogle Scholar
  100. 100.
    Otto EA, Trapp ML, Schultheiss UT, Helou J, Quarmby LM, Hildebrandt F. NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J Am Soc Nephrol. 2008;19:587–92.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Morgan NV, Bacchelli C, Gissen P, Morton J, Ferrero GB, Silengo M, et al. A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13. J Med Genet. 2003;40:431–5.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Beales PL, Bland E, Tobin JL, Bacchelli C, Tuysuz B, Hill J, et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet. 2007;39:727–9.PubMedGoogle Scholar
  103. 103.
    Dagoneau N, Goulet M, Geneviève D, Sznajer Y, Martinovic J, Smithson S, et al. DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III. Am J Hum Genet. 2009;84:706–11.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Davis EE, Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, et al. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat Genet. 2011;43:189–96.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Bredrup C, Saunier S, Oud MM, Fiskerstrand T, Hoischen A, Brackman D, et al. Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19. Am J Hum Genet. 2011;89:634–43.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Baujat G, Huber C, El Hokayem J, Caumes R, Do Ngoc Thanh C, David A, et al. Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families. J Med Genet. 2013;50:91–8.PubMedGoogle Scholar
  107. 107.
    Schmidts M, Vodopiutz J, Christou-Savina S, Cortes CR, McInerney-Leo AM, Emes RD, et al. Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy. Am J Hum Genet. 2013;93:932–44.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Sampson JR, Maheshwar MM, Aspinwall R, Thompson P, Cheadle JP, Ravine D, et al. Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 Gene. Am J Hum Genet. 1997;61:843–51.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Shiba D, Manning DK, Koga H, Beier DR, Yokoyama T. Inv acts as a molecular anchor for Nphp3 and Nek8 in the proximal segment of primary cilia. Cytoskeleton (Hoboken). 2010;67:112–9.Google Scholar
  110. 110.
    Fukui H, Shiba D, Asakawa K, Kawakami K, Yokoyama T. The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish. FEBS Lett. 2012;586:2273–9.PubMedGoogle Scholar
  111. 111.
    Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, et al. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013;45:951–6.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Peters M, Jeck N, Reinalter S, Leonhardt A, Tönshoff B, Gü KG, et al. Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med. 2002;112:183–90.PubMedGoogle Scholar
  113. 113.
    Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, et al. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005;37:964–8.PubMedGoogle Scholar
  114. 114.
    Alpert SA, Noe HN. Furosemide nephrolithiasis causing ureteral obstruction and urinoma in a preterm neonate. Urology. 2004;64:589.PubMedGoogle Scholar
  115. 115.
    Hein G, Richter D, Manz F, Weitzel D, Kalhoff H. Development of nephrocalcinosis in very low birth weight infants. Pediatr Nephrol. 2004;19:616–20.PubMedGoogle Scholar
  116. 116.
    Amann K, Plank C, Dotsch J. Low nephron number—a new cardiovascular risk factor in children? Pediatr Nephrol. 2004;19:1319–23.PubMedGoogle Scholar
  117. 117.
    Latini G, De Mitri B, Del Vecchio A, Chitano G, DeFelice C, Zetterstrom R. Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: “programming” causing “metabolic syndrome” in adult age. Acta Paediatr. 2004;93:1635–9.PubMedGoogle Scholar
  118. 118.
    Martinovic J, Benachi A, Laurent N, Daikha-Dahmane F, Encha-Razavi F, Gubler MC. Toxic effects of Angiotensin-II receptor antagonists. Report of three additional cases. Lancet. 2001;358:241–2.PubMedGoogle Scholar
  119. 119.
    Risdon RA. Diseases of the kidney and lower urinary tract. In: Berry CL, editor. Paediatric pathology. Berlin: Springer; 1981. p. 395–450.Google Scholar
  120. 120.
    Risdon RA. Reflux nephropathy. Diagn Histopathol. 1981;4:61–70.PubMedGoogle Scholar
  121. 121.
    Jaswon MS, Dibble L, Puri S, et al. Prospective study of outcome in antenatally diagnosed renal pelvis dilatation. Arch Dis Child Fetal Neonatal Ed. 1999;80:F135–8.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Cohen-Overbeek TE, Wijngaard-Boom P, Ursem NTC, Hop WCJ, Wladimiroff JW, Wolffenbuttel KP. Mild renal pyelectasis in the second trimester: determination of cut-off levels for postnatal referral. Ultrasound Obstet Gynecol. 2005;25:378–83.PubMedGoogle Scholar
  123. 123.
    Nakai H, Asanuma H, Shishido S, Kitahara S, Yasuda K. Changing concepts in urological management of the congenital anomalies of kidney and urinary tract, CAKUT. Pediatr Int. 2003;45:634–41.PubMedGoogle Scholar
  124. 124.
    Berrocal T, Lopez-Pereira P, Arjonilla A, Gutierrez J. Anomalies of the distal ureter, bladder, and urethra in children: embryologic, radiologic, and pathologic features. Radiographics. 2002;22:1139–64.PubMedGoogle Scholar
  125. 125.
    Zerin JM, Baker DR, Casale JA. Single-system ureteroceles in infants and children: imaging features. Pediatr Radiol. 2000;30:139–46.PubMedGoogle Scholar
  126. 126.
    Afshar K, Malek R, Bakhshi M, et al. Should the presence of congenital para-ureteral diverticulum affect the management of vesicoureteral reflux? J Urol. 2005;174:1590–3.PubMedGoogle Scholar
  127. 127.
    Verbruggen SC, Wijnen RM, van den Berg P. Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report. J Matern Fetal Neonatal Med. 2004;16:140–1.PubMedGoogle Scholar
  128. 128.
    Bae KS, Jeon SH, Lee SJ, et al. Complete duplication of bladder and urethra in coronal plane with no other anomalies: case report with review of the literature. Urology. 2005;65:388.PubMedGoogle Scholar
  129. 129.
    Stein RJ, Matoka DJ, Noh PH, Docimo SG. Spontaneous perforation of congenital bladder diverticulum. Urology. 2005;66:881.PubMedGoogle Scholar
  130. 130.
    Ochoa B. Can a congenital dysfunctional bladder be diagnosed from a smile? The Ochoa syndrome updated. Pediatr Nephrol. 2004;19:6–12.PubMedGoogle Scholar
  131. 131.
    Reutter H, Shapiro E, Gruen JR. Seven new cases of familial isolated bladder exstrophy and epispadias complex (BEEC) and review of the literature. Am J Med Genet A. 2003;120:215–21.Google Scholar
  132. 132.
    Nelson CP, Dunn RL, Wei JT. Contemporary epidemiology of bladder exstrophy in the United States. J Urol. 2005;173:1728–31.PubMedGoogle Scholar
  133. 133.
    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;99:261–9.PubMedGoogle Scholar
  134. 134.
    Froster UG, Heinritz W, Bennek J, Horn LC, Faber R. Another case of autosomal dominant exstrophy of the bladder. Prenat Diagn. 2004;24:375–7.PubMedGoogle Scholar
  135. 135.
    Kallen K, Castilla EE, Robert E, Mastroiacovo P, Kallen B. OEIS complex—a population study. Am J Med Genet. 2000;92:62–8.PubMedGoogle Scholar
  136. 136.
    Keppler-Noreuil KM. OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): a review of 14 cases. Am J Med Genet. 2001;99:271–9.PubMedGoogle Scholar
  137. 137.
    Kiddoo DA, Carr MC, Dulczak S, Canning DA. Initial management of complex urological disorders: bladder exstrophy. Urol Clin N Am. 2004;31:417–26.Google Scholar
  138. 138.
    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;172:1103–6.PubMedGoogle Scholar
  139. 139.
    Wood HP, Trock BP, Gearhart JP. In vitro fertilization and the cloacal-bladder exstrophy epispadias complex: is there an association? J Urol. 2003;169:1512–5.PubMedGoogle Scholar
  140. 140.
    Krishnan A, de Souza A, Konijeti R, Baskin LS. The anatomy and embryology of posterior urethral valves. J Urol. 2006;175:1214–20.PubMedGoogle Scholar
  141. 141.
    Cremin BJ. Infantile thoracic dystrophy. Br J Radiol. 1970;43:199–204.PubMedGoogle Scholar
  142. 142.
    Wigglesworth JS. Perinatal pathology. Philadelphia: WB Saunders; 1984.Google Scholar
  143. 143.
    Jones EA, Freedman AL, Ehrlich RM. Megalourethra and urethral diverticula. Urol Clin N Am. 2002;29:341–8.Google Scholar
  144. 144.
    Wigger HJ, Blanc WA. The prune belly syndrome. Pathol Annu. 1977;12:17–39.PubMedGoogle Scholar
  145. 145.
    Pierik FH, Burdorf A, Nijman JM, de Muinck Keizer-Schrama SM, Juttmann RE, Weber RF. A high hypospadias rate in The Netherlands. Hum Reprod. 2002;17:1112–5.PubMedGoogle Scholar
  146. 146.
    Ahmed SF, Dobbie R, Finlayson AR, Gilbert J, Youngson G, Chalmers J, Stone D. Prevalence of hypospadias and other genital anomalies among singleton births, 1988–1997, in Scotland. Arch Dis Child Fetal Neonatal Ed. 2004;89:F149–51.PubMedPubMedCentralGoogle Scholar
  147. 147.
    Martinez-Frías ML, Prieto D, Prieto L, Bermejo E, Rodríguez-Pinilla E, Cuevas L. Secular decreasing trend of the frequency of hypospadias among newborn male infants in Spain. Birth Defects Res A Clin Mol Teratol. 2004;70:75–81.PubMedGoogle Scholar
  148. 148.
    Manson JM, Carr MC. Molecular epidemiology of hypospadias: review of genetic and environmental risk factors. Birth Defects Res A Clin Mol Teratol. 2003;67:825–36.PubMedGoogle Scholar

Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  1. 1.Department of Embryo-Fetal PathologyParis-Sud University Group of Schools of Medicine, AP-HP, Antoine Béclère HospitalParisFrance

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