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Nephrotic syndrome in the 1st year of life

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Abstract

Among the various primary conditions which may be associated with a nephrotic syndrome at birth or within the 1st year of life, the best known is the congenital nephrotic syndrome of finnish type (CNF) characterized by irregular pseudocystic dilatation of proximal tubules. This disease, very frequent in Finaland, is often familial with an autosomal recessive mode of inheritance. Patients are steroid resistant, but the cause of death is usually not uraemia but infection or severe diarrhoea with electrolyte imbalance. The second condition is idiopathic nephrosis including minimal change disease, diffuse mesangial proliferation and focal segmental glomerular sclerosis. As opposed to CNF, infants with “early onset nephrosis” may respond to steroid therapy as older children do and may even recover. However, there are no histopathological criteria which allow the certain differentiation of idiopathic nephrosis from CNF. The third condition is diffuse mesangial sclerosis (DMS), a clinicopathological entity which can occur as an isolated finding or be associated with male pseudohermaphroditism and/or Wilms' tumour (Drash syndrome). From a morphological point of view, DMS is easy to differentiate from CNF because of the characteristic pattern of involvement of the glomeruli. From a clinical point of view, the nephropathy, almost always characterized by a nephrotic syndrome, has two distinct features: it is most often diagnosed in the first 2 years of life and it progresses rapidly to end-stage renal failure, which usually occurs before the age of 3 years. The clinical findings in 36 patients with DMS are presented. The nephropathy was isolated in 22 infants and associated with male pseudohermaphroditism and/or Wilms' tumour in 14. The early onset of the nephropathy, its familial incidence and its association with Drash syndrome suggests an antenatal dysgenetic process. Recent studies indicate a direct role of WT1 (a Wilms' tumour gene) in the aetiology of Drash syndrome, and mutations of this gene have been found in 3 patients herein reported. It remains to be demonstrated whether or not the WT1 gene is also altered in patients with isolated DMS.

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References

  1. Hallman N, Hjelt L (1959) Congenital nephrotic syndrome. J Pediatr 55: 152–157

    Google Scholar 

  2. Habib R, Bois E (1973) Hétérogénéité des syndromes néphrotiques à début précoce du nourrisson (Syndrome néphrotique “infantile”). Helv Paediatr Acta 28: 91–107

    Google Scholar 

  3. Hallman N, Norio R, Rapola J (1973) Congenital nephrotic syndrome. Nephron 11: 101–110

    Google Scholar 

  4. Kaplan BS, Bureau MA, Drummond KN (1974) The neprotic syndrome in the first year of life: is a pathologic classification possible? J Pediatr 85: 615–621

    Google Scholar 

  5. Schneller P, Braga SE, Moser H, Zimmermann A, Oetliker O (1983) Congenital nephrotic syndrome: clinicopathological heterogeneity and prenatal diagnosis. Clin Nephrol 19: 243–249

    Google Scholar 

  6. Sibley RK, Mahan J, Mauer SM, Vernier RL (1985) A clinicopathologic study of forty eight infants with nephrotic syndrome. Kidney Int 27: 544–552

    Google Scholar 

  7. Habib R, Loirat C, Gubler MC, Niaudet P, Bensman A, Levy M, Broyer M (1985) The nephropathy associated with male pseudoher maphroditism and Wilms' tumor (Drash syndrome): a distinctive glomerular lesion, report of 10 cases. Clin Nephrol 24: 269–278

    Google Scholar 

  8. Mahan JD, Mauer SM, Sibley RK, Vernier RC (1984) Congenital nephrotic syndrome: the evolution of medical management and results of renal transplantation. J Pediatr 105: 548–557

    Google Scholar 

  9. Vernier RL, Klein DJ, Sisson SP, Mahan JD, Oegena TR, Brown DM (1983) Heparan sulfate-rich anionic sites in the human glomerular basement membrane. Decreased concentration in congenital nephrotic syndrome. N Engl J Med 309: 1001–1009

    Google Scholar 

  10. Vermylen C, Levin M, Mossman J, Barratt TM (1989) Glomerular and urinary heparan sulfate in congenital nephrotic syndrome. Pediatr Nephrol 3: 122–129

    Google Scholar 

  11. Kjessler B, Hultquist G, Johannsson SGO, Sherman MS, Gustavson KH (1977) Antenatal diagnosis of congenital nephrosis of Finnish type. Acta Obstet Gynecol Scand [Suppl] 69: 59–77

    Google Scholar 

  12. Wiggelinkhuisen J, Melson MM, Berger GBM, Kaschula ROC (1976) Alphafetoprotein in the antenatal diagnosis of the congenital nephrotic syndrome. J Pediatr 89: 452–455

    Google Scholar 

  13. Norio R (1966) Heredity in the congenital nephrotic syndrome: a genetic study of 57 Finnish families with a review of reported cases. Ann Paediatr Fenniae 12 [Suppl 27]: 1–94

    Google Scholar 

  14. Seelig H, Seelig R, Schärer K (1975) Immunohistologische Untersuchungen bei der diffusen mesangialen sklerose mit nephrotischen Syndrom im Säuglingsalter. Z Kinderheilkd 120: 111–120

    Google Scholar 

  15. Beale MC, Staver DS, Kissane JM, Robson AM (1979) Congenital glomerulosclerosis and nephrotic syndrome in 2 infants. Am J Dis Child 133: 842–845

    Google Scholar 

  16. Rumpelt HJ, Bachmann HJ (1980) Infantile nephrotic syndrome with diffuse mesangial sclerosis: a disturbance of glomerular basement membrane development? Clin Nephrol 13: 146–150

    Google Scholar 

  17. Uraoka YR, Murata R, Maki S, Sakatani K (1981) Infantile nephrotic syndrome. Report of an infant with diffuse mesangial sclerosis. Acta Med Kinki Univ 6: 7–18

    Google Scholar 

  18. Khrouf N, Koraichi H, Brauner R, Ben Julani S, Hamza M, Hamza B (1982) Les syndromes néphrotiques infantiles. A propos de 6 cas observés en Tunisie. Ann Pediatr (Paris) 29: 215–218

    Google Scholar 

  19. Mendelsohn HB, Krauss M, Berant M, Lichtig C (1982) Familial early-onset nephrotic syndrome: diffuse mesangial sclerosis. Acta Paediatr Scan 71: 753–758

    Google Scholar 

  20. Kristal H, Lichtig C (1983) Infantile nephrotic syndrome. Clinicopathological study of 11 cases. Isr J Med Sci 19: 626–630

    Google Scholar 

  21. Kikuta Y, Yoshimura Y, Saito T, Ishihara T, Tokoyama S, Hayashi T (1983) Nephrotic syndrome with diffuse mesangial sclerosis in identical twins. J Pediatr 102: 586–588

    Google Scholar 

  22. Gaudelius J, Leverger G, Rault G, Nathanson M, Giorno JL, Boccon-Gibod L, Levy M, Broyer M (1984) Association d'un syndrome néphrotique à début précoce et d'une microcéphalie. A propos de 4 observations dans 2 familles. Arch Fr Pediatr 41: 409–415

    Google Scholar 

  23. Urbach, J, Drukher A, Rosenmann E (1985) Diffuse mesangial sclerosis, light, immunofluorescent and electron microscopy findings. Int J Pediatr Nephrol 6: 101–104

    Google Scholar 

  24. Eggert Von W, Eggert S, Discherlein G, Grossmann P, Devaux S (1987) Die mesangiumskleorse als Ursache des familiären nephrotischen Syndroms. Kinderärztl Prax 55: 295–302

    Google Scholar 

  25. Martul EV, Cuesta MG, Churg J (1987) Histopathologic variability of the congenital nephrotic syndrome. Clin Nephrol 28: 161–168

    Google Scholar 

  26. Gill DG (1988) Clinicopathological quiz. Pediatr Nephrol 2: 378–380

    Google Scholar 

  27. Parchoux B, Bourgeois J, Gilly J, Barral G, Guibaud P, Larbre F, Bethenod M (1988) Gros reins in utero et insuffisance rénal néonatale par sclérose mésangiale diffuse. Pediatrie 43: 219–222

    Google Scholar 

  28. Spear GS, Steinhaus KA, Quddusi A (1991) Diffuse mesangial sclerosis in a fetus. Clin Nephrol 36: 46–48

    Google Scholar 

  29. Koskimies O, Sariola H, Holmerg C, Rapola J (1991) Clinical quiz. Pediatr Nephrol 5: 433–435

    Google Scholar 

  30. Denys P, Malvaux P, Van den Berghe H, Tanghe W, Proesmans W (1967) Association d'un syndrome anatomopathologique de pseudohermaphrodisme masculin, d'une tumeur de Wilms, d'une néphropathie parenchymateuse et d'un mosaicisme XX/XY. Arch Fr Pediatr 24: 729–739

    Google Scholar 

  31. Drash A, Sherman F, Hartmann W, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms' tumor, hypertension and degenerative renal disease. J Pediatr 76: 585–593

    Google Scholar 

  32. Smith NJ (1946) Glomerulonephritis, Wilms tumor and horseshoe kidney in an infant. Arch Pathol 42: 549–554

    Google Scholar 

  33. Zunin C, Soave F (1964) Association of nephrotic syndrome and nephrobalstoma in siblings. Ann Pediatr (Paris) 203: 29–38

    Google Scholar 

  34. Grupe WE, Cuppage FD, Heymann W (1966) Congenital neprotic syndrome with interstitial nephritis. Am J Dis Child 111: 482–489

    Google Scholar 

  35. Spear G, Hyde TP, Gruppo RA, Slusser R (1971) Pseudohermaphroditism, glomerulonephritis with the nephrotic syndrome and Wilms' tumor in infancy. J Pediatr 79: 677–681

    Google Scholar 

  36. Barakat AY, Papadopoulo ZL, Chandra RTS, Hollerman CE, Calcagno PL (1974) Pseudohermaphroditism, nephron disorder and Wilms tumor: a unifying concept. Pediatrics 54: 366–369

    Google Scholar 

  37. McReynolds EW, Roys S III, Etteldorf J (1974) Congenital nephrotic syndrome with ambiguous genitalia. Postgrad Med 55: 201–202

    Google Scholar 

  38. Gotloib L, London R, Rosenmann E (1976) Infantile nephrotic syndrome due to glomerulonephritis in a male pseudohermaphrodite Isr J Med Sci 12: 52–58

    Google Scholar 

  39. Feiner HD, Camuto P, Wolman SR (1978) Subclinical Wilm's tumor in incomplete Drash syndrome (letter). Hum Pathol 18: 1077

    Google Scholar 

  40. Wolff OH, Barratt JM, Pincott J, Cameron JS, Black D, Milne MD, MacRae JHH, Dillon MHJ, Brown MJ, Jepson EM (1987) Two children with kidney disease. BMJ 2: 867–872

    Google Scholar 

  41. Chattas AJ, Delgado N, Gallo GE, Shwartzmann E, Canepa C, Sojo ET (1979) Associacion de tumor de Wilms, pseudohermaphroditisme y nefropatia glomerular. Bol Med Hosp Infant Mex 36: 1203–1212

    Google Scholar 

  42. Chang GH, Brough AJ, Perrin E, Primak N, Fleischmann L (1979) A nephron disorder associated with Wilms' tumor (abstract). Pediatr Res 13: 511

    Google Scholar 

  43. Carter JE, Dimmick JE, Lirenman DS (1980) Congenital nephrosis with gonadal dysgenesis in twins (abstract). Pediatr Res 14: 1044

    Google Scholar 

  44. Gertner JM, Kauschansky A, Giesber DW, Siegel NU, Breg WR, Genel M (1980) XY gonadal dysgenesis associated with the congenital nephrotic syndrome. Obstet Gynecol [Suppl] 55: 66–69

    Google Scholar 

  45. Goldman SM, Garfinkel DJ, Oh KS, Dorst JP (1981) The Drash syndrome: male pseudohermaphroditsm, nephritis and Wilms' tumor. Pediatr Radiol 141: 87–91

    Google Scholar 

  46. Ringert RH, Pistor K (1982) Nephroblastoma associated with mesangioproliferative glomerulonephritis. Eur Urol 8: 125–126

    Google Scholar 

  47. Fisher JE, Andres GA, Cooney DR, MacDonald M (1983) Syndrome of pure gonadal dysgenesis: gonadoblastoma, Wilms' tumor and nephron disease (abstract). Lab Invest 48: 4P

  48. Houghton DC, Ridgeway D, Talwalker Y (1983) Association of Wilms' tumor and sclerosing glomerulonephritis (abstract). Kidney Int 23: 194

    Google Scholar 

  49. Keneko M, Saito S, Tsuchida Y, Nakajo T, Akiyama M (1983) Wilms' tumor, nephron disorder and ambiguous genitalia. Kinderchir 38: 345–349

    Google Scholar 

  50. McCoy FE, Franklin WA, Aronson AJ, Spargo BH (1983) Glomerulonephritis associated with male pseudohermaphroditism and nephroblastoma. Am J Surg Pathol 7: 387–395

    Google Scholar 

  51. Behesti M, Mancer JFK, Hardy BE, Churchill BM, Bailey JD (1984) External genital abnormalities associated with Wilms' tumor. Urology 24: 130–133

    Google Scholar 

  52. Koyanagi T, Hirama M, Taniguchi K, Gotoh T, Inoue K, Maru A, Tsuji I (1984) Wilms' tumor and nephrotic syndrome in male pseudohermaphroditism. Urology 24: 595–600

    Google Scholar 

  53. Thorner P, McGraw M, Weitzman S, Balfe JW, Klein M, Baumal R (1984) Wilms' tumor and glomerular disease. Arch Pathol Lab Med 108: 141–146

    Google Scholar 

  54. Eddy AA, Mauer SM (1985) Pseudohermaphroditism, glomerulopathy and Wilms' tumor (Drash syndrome): frequency in end stage renal failure. J Pediatr 106: 584–587

    Google Scholar 

  55. Angus B, Bayliss AP, Catto GRD, Ewen SWB, Gray ES, Miller SS, Simpson JG, Smail PJ (1985) Rapidly progressive renal failure in a child. Scott Med J 30: 184–189

    Google Scholar 

  56. Waldherr R, Ostertag-Körner D (1985) Wilms' tumor and glomerulopathy. (letter) Arch Pathol Lab Med 109: 7

    Google Scholar 

  57. Friedman AL, Finlay JL (1987) The Drash syndrome revisited: diagnosis and follow-up. Am J Med Genet [Suppl] 3: 293–296

    Google Scholar 

  58. Gallo GB, Chemes HE (1987) The association of Wilm's tumor, male pseudohermaphroditism and diffuse glomerular disease (Drash syndrome): report of 8 cases with clinical and morphologic findings and review of the literature. Pediatr Pathol 7: 175–189

    Google Scholar 

  59. Manivel JC, Sibley RK, Dehner LP (1987) Complete and incomplete Drash syndrome: a clinical pathologic study of 5 cases of a dysontogenetic neoplastic complex. Hum Pathol 18: 80–89

    Google Scholar 

  60. Loirat C, Sonsino E (1988) Syndromes néphrotiques congénliaux et infantiles. In.: JPP Flannarion Medecine Scieces Paris 131–140

  61. Jadresic L, Leake J, Gordon I, Dillon MJ, Grant DB, Pritchard J, Risdon RA (1990) Clinicopathologic review of twelve children with nephropathy, Wilms' tumor and genital abnormalities (Drash syndrome). J Pediatr 117: 717–725

    Google Scholar 

  62. Turleau C, Grouchy J de, Tournade MF, Gagnadoux MF, Junien C (1984) Del 11p/aniridia complex. Report of 3 patients and review of 37 observations from the literature. Clin Genet 26: 336–362

    Google Scholar 

  63. Case Records of the Massachusett General Hospital (1985) Case 17-1985. N Engl J Med 321: 1111–1119

    Google Scholar 

  64. Welch TR, McAdams AJ (1986) Focal glomerulosclerosis as a late sequela of Wilms tumor. J Pediatr 108: 105–109

    Google Scholar 

  65. Gusmano R, Perfumo F, Raspino M, Ginevri F, Ferretti A (1987) Nephropathy associated with Wilms' tumor. A case of a 13-year-old girl. Nephron 45: 242–246

    Google Scholar 

  66. Moorthy AV, Chesnay RW, Lubinsky M (1987) Chonic renal failure and XY gonadal dysgenesis: Frasier syndrome, a commentary on reported cases. Am J Med Genet [Suppl] 3: 297–302

    Google Scholar 

  67. Frasier SD, Bashore RA, Mosier HD (1964) Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins. J Pediatr 64: 740–745

    Google Scholar 

  68. Blanchet P, Daloze P, Lesage R, Papas S, Van Capenhout J (1977) XY gonadal dysgenesis with gonadoblastoma discovered after kidney transplantation. Am J Obstet Gynecol 129: 221–222

    Google Scholar 

  69. Simpson JL, Chaganti RSK, Mouradian J, German J (1982) Chronic renal disease, myotonic dystrohy and gonadoblastoma in XY gonadal dysgenesis. J Med Genet 19: 73–76

    Google Scholar 

  70. Harkins PG, Haning RV, Shapiro SS (1980) Renal failure with XY gonadal dysgenesis. Report of the second case. Obstet Gynecol 56: 751–752

    Google Scholar 

  71. Haning RV, Chesney RW, Moorthy AV, Gilbert EF (1985) A syndrome of chonic renal failure and XY gonadal dysgenesis in young phenotypic females without genital ambiguity. Am J Kidney Dis 6: 40–48

    Google Scholar 

  72. Habib R, Gubler MC, Antignac C, Loirat C, Gagnadoux MF (1989) Nephropathy associated with Wilms' tumor. Pediatr Nephrol 3: C32

    Google Scholar 

  73. Habib R, Gubler MC, Antignac C, Loirat C, Gagnadoux MF (1990) Syndrome néprotique congénital ou infantile avec sclérose mésangiale diffuse. Ann Pediatr (Paris) 37: 73–77

    Google Scholar 

  74. Weinberg RA (1991) Tumor suppressor genes. Science 254: 1138–1146

    Google Scholar 

  75. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cen 60: 509–520

    Google Scholar 

  76. Gessler M, Pouska A, Cavenee W, Neve RL, Orkin SH, Bruns GAP (1990) Homozygous deletion in Wilms' tumours of a zinc-finger gene identified by chromosome jumping. Nature 343: 774–778

    Google Scholar 

  77. Pritchard Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D, Heyningen V van, Hastie N (1990) The candidate Wilms' tumour gene is involved in genito-urinary development. Nature 346: 194–197

    Google Scholar 

  78. Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE (1990) An internal deletion within an llp 13 zinc finger gene contributes to the development of Wilms' tumor. Cell 61: 1257–1269

    Google Scholar 

  79. Huff V, Miwa H, Haber DA, Call KM, Houman D, Strong LC, Saunders GF (1991) Evidence for WT1 as a Wilms tumor (WT) gene: intragenic deletion in bilateral WT. Am J Hum Genet 48: 997–1003

    Google Scholar 

  80. Pelletier J, Bruening W, Li FP, Haber DA, Glaser T, Housman DE (1991) WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumor. Nature 353: 431–434

    Google Scholar 

  81. Jadresic L, Wadey RB, Buckle B, Barratt TM, Mitchell CD, Cowell JK (1991) Molecular analysis of chromosome region 11p13 in patients with Drash syndrome. Hum Genet 86: 497–501

    Google Scholar 

  82. pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel, JC, Striegel JE, Haughton DC, Junien C, Habib R, Fouser L, Fine RN, Silverman BL, Haber DA, Housman D (1991) Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67: 437–447

    Google Scholar 

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    Renée Habib

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Habib, R. Nephrotic syndrome in the 1st year of life. Pediatr Nephrol 7, 347–353 (1993). https://doi.org/10.1007/BF00857534

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