Pediatric Nephrology

, Volume 28, Issue 12, pp 2313–2321 | Cite as

Congenital nephrotic syndrome with prolonged renal survival without renal replacement therapy

  • William WongEmail author
  • Maxwell Clarke Morris
  • Tonya Kara
Original Article



Infants with congenital nephrotic syndrome (CNS) develop severe nephrotic syndrome that is resistant to medical therapy, and bilateral nephrectomy is recommended toward the end of the first year of life followed by renal replacement therapy. CNS infants in New Zealand have been observed to exhibit a different course to those with the typical Finnish mutation.


A database of CNS children at our center was retrospectively examined. All cases diagnosed between 1975 and 2011 were reviewed. Demographic data, clinical features, genetic mutations, treatment, and outcome were extracted from clinical records.


Thirty-five patients with CNS, 23 children of Maori descent, and 12 Caucasians . Fourteen had died of either bacterial sepsis or intracranial thrombosis. Maori children had displayed a highly variable and protracted timeline to end-stage renal disease (ESRD) with median renal survival of 30 years versus 0.7 years in Caucasian patients. Mutation analysis of NPHS1 showed a founder mutation in the Maori population.


Congenital nephrotic syndrome in New Zealand Maori children exhibit a different clinical course to Caucasian children and have a mutation that was first described in this ethnic group.


NPHS1 Congenital nephrotic syndrome Maori Mutational analysis Children 



The authors wish to thank the funding support of Kidney Kids (NZ) Inc. for the nephrin mutation analysis and all the renal physicians who have permitted participation of their patients diagnosed to have congenital nephrotic syndrome. The authors also wish to thank the Nijmegen Genetics Centre, Radboud University, Nijmegen, The Netherlands, for undertaking the genetic analysis and Dr. Juliet Taylor, Clinical Geneticist, Northern Regional Genetics Service for comments and prediction tools. This study was presented in part at the 15th Congress of the International Pediatric Nephrology Association, New York, August 29 to September 2, 2010.


  1. 1.
    Jalanko H (2009) Congenital nephrotic syndrome. Pediatr Nephrol 24:2121–2128PubMedCrossRefGoogle Scholar
  2. 2.
    Kestila M, Mannikko M, Holmberg C, Gyapay G, Weissenbach J, Savolainen ER, Peltonen L, Tryggvason K (1994) Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19. Am J Hum Genet 54:757–764PubMedGoogle Scholar
  3. 3.
    Patrakka J, Kestila M, Wartiovaara J, Ruotsalainen V, Tissari P, Lenkkeri U, Mannikko M, Visapaa I, Holmberg C, Rapola J, Tryggvason K, Jalanko H (2000) Congenital nephrotic syndrome (NPHS1): features resulting from different mutations in Finnish patients. Kidney Int 58:972–980PubMedCrossRefGoogle Scholar
  4. 4.
    Heeringa SF, Vlangos CN, Chernin G, Hinkes B, Gbadegesin R, Liu J, Hoskins BE, Ozaltin F, Hildebrandt F, Members of the APN Study Group (2008) Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome. Nephrol Dial Transplant 23:3527–3533PubMedCrossRefGoogle Scholar
  5. 5.
    Hinkes B, Mucha B, Vlango CN, Gbadegesin R, Liu J, Hasselbacher K, Hangan D, Ozaltin F, Zenker M, Hildebrandt F, Members of the Arbeitsgemeinschaft für Paediatrische Nephrologie Study Group (2007) Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, Wt1 and LAMB2). Pediatrics 119:e907–e919PubMedCrossRefGoogle Scholar
  6. 6.
    Mrowka C, Schedul A (2000) Wilm’s tumour gene WT1: from structure to renal pathophysiologic features. J Am Soc Nephrol 11:S106–S115PubMedGoogle Scholar
  7. 7.
    Matejas V, Hinkes B, Alkandari F, Al-Gazali L, Annexstad E, Aytac MB, Barrow M, Kvĕta B, Bockenhauer D, Cheong H, Maruniak-Chudek I, Cochat P, Dötsch J, Gajjar P, Hennekam RC, Françoise Janssen F, Kagan M, Kariminejad A, Kemper MJ, Koenig J, Kogan J, Kroes HY, Kuwertz-Bröking E, Lewanda AF, Medeira A, Muscheites J, Niaudet P, Pierson M, Saggar A, Seaver L, Suri M, Tsygin A, Wühl E, Zurowska A, Uebe S, Hildebrandt F, Antignac C, Zenker M (2010) Mutations in the human laminin β2 (LAMB2) gene and the associated phenotypic spectrum. Human Mutat 31:992–1002CrossRefGoogle Scholar
  8. 8.
    Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, Loirat C, Ozaltin F, Hashmi S, Ulmer F, Cleper R, Ettenger R, Antignac C, Wiggins RC, Zenker M, Hildebrandt F (2008) Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant 23:1291–1297PubMedCrossRefGoogle Scholar
  9. 9.
    Heaton PA, Smales O, Wong W (1999) Congenital nephrotic syndrome responsive to captopril and indomethacin. Arch Dis Child 81:174–175PubMedCrossRefGoogle Scholar
  10. 10.
    Pomeranz A, Wolach B, Bernheim J, Korzets Z, Bernheim J (1995) Successful treatment of Finnish congenital nephrotic syndrome with captopril and indomethacin. J Pediatr 126:140–142PubMedCrossRefGoogle Scholar
  11. 11.
    Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998) Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell 1:575–582PubMedCrossRefGoogle Scholar
  12. 12.
    Guez S, Giani M, Melzi ML, Antignac C, Assael BM (1998) Adequate clinical control of congenital nephrotic syndrome by enalapril. Pediatr Nephrol 12:130–132PubMedCrossRefGoogle Scholar
  13. 13.
    Kovacevic L, Reid CJ, Ridgen SPA (2003) Management of congenital nephrotic syndrome. Pediatr Nephrol 18:426–430PubMedCrossRefGoogle Scholar
  14. 14.
    Finn LS, Symons JM, Smith JS (2003) Nephrotic syndrome in the newborn. Am J Kid Dis 42:1318–1323PubMedCrossRefGoogle Scholar
  15. 15.
    Lui L, Doné SC, Koshnoodi J, Bertorello A, Wartiovaara J, Berggren P, Tryggvason K (2001) Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insights into mechanisms of congenital nephroitc syndrome. Hum Mol Gen 10:2637–2644CrossRefGoogle Scholar
  16. 16.
    Fuchshuber A, Niaudet P, Gribouval O, Jean G, Gubler MC, Broyer M, Antignac C (1996) Congenital nephrotic syndrome of the Finnish type: linkage to the locus in a non-Finnish population. Pediatr Nephrol 10:135–138PubMedGoogle Scholar
  17. 17.
    Bolk S, Puffenberger EG, Hudson J, Morton DH, Chakravarti A (1999) Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome, Finnish type, in the Old Order Mennonites. Am J Hum Genet 65:1785–1790PubMedCrossRefGoogle Scholar
  18. 18.
    Beltcheva O, Martin P, Lenkkeri U, Tryggvason K (2001) Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome. Hum Mutat 17:368–373PubMedCrossRefGoogle Scholar
  19. 19.
    Machuca E, Benoit G, Nevo F, Tête MJ, Gribouval O, Pawtowski A, Brandström P, Loirat C, Niaudet P, Gubler MC, Antignac C (2010) Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. J Am Soc Nephrol 21:1209–1217PubMedCrossRefGoogle Scholar
  20. 20.
    Ovunc B, Ashraf S, Vega-Warner V, Bockenhauer D, Elshakhs NA, Joseph M, Hildebrandt F, Gesellschaft für Pädiatrische Nephrologie (GPN) (2012) Study group mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patients. Nephron Clin Pract 120:c139–c146PubMedCrossRefGoogle Scholar
  21. 21.
    Lemley KV (2006) Neonatal nephrotic presentation of child with a heterozygous NPHS1 mutation. Pediatr Nephrol 6:864–866CrossRefGoogle Scholar
  22. 22.
    Gigante M, Defazio V, Iolascon A, Gesualdo L, Wong W (2007) Identification of new NPHS1 mutations and detection of founder-effect haplotype in New Zealand families with congenital nephrotic syndrome of the Finnish type. Nephrol Dial Transplant 22:vi36, FP057Google Scholar
  23. 23.
    Philippe A, Nevo F, Esquivel EL, Reklaityte D, Gribouval O, Tête MJ, Loirat C, Dantal J, Fischbach M, Pouteil-Noble C, Decramer S, Hoehne M, Benzing T, Charbit M, Niaudet P, Antignac C (2008) Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome. J Am Soc Nephrol 19:1871–1878PubMedCrossRefGoogle Scholar
  24. 24.
    Goldenrod N, Dahan K (2010) Expanding the clinical spectrum of congenital nephrotic syndrome caused by NPHS1 mutations. Nephrol Dial Transplant 25:2837–2839CrossRefGoogle Scholar
  25. 25.
    Schoeb DS, Chernin G, Heeringa SF, Matejas V, Held S, Vega-Warner V, Bockenhauer D, Vlangos CN, Moorani KN, Neuhaus TJ, Kari JA, MacDonald J, Saisawat P, Ashraf S, Ovunc B, Zenker M, Hildebrandt F, Gesellschaft für Paediatrische Nephrologie (GPN) Study Group (2010) Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS). Nephrol Dial Transplant 25:2970–2976PubMedCrossRefGoogle Scholar
  26. 26.
    Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P (2002) Genotype/phenotype correlations with NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. Hum Mol Genet 11:378–388CrossRefGoogle Scholar
  27. 27.
    Hassellbacher K, Wiggins RC, Matejas V (2006) Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2 associated kidney disorders. Kidney Int 70:1008–1012CrossRefGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  • William Wong
    • 1
    Email author
  • Maxwell Clarke Morris
    • 1
  • Tonya Kara
    • 1
  1. 1.Department of NephrologyStarship Children’s HospitalAucklandNew Zealand

Personalised recommendations