Skip to main content
SpringerLink
Log in

Genetics of congenital and infantile nephrotic syndrome

  • Original Article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations. This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution. We also discussed our different approach secondary to culture and resources.

Methods

A retrospective single-center study of all children diagnosed as NS before the age of 1 year over a duration of over one decade.

Results

Twenty-nine children (12 boys) were included in the study. Their median age (range) was 2.4 (0.1–12) months (20 CNS and 9 INS). Consanguinity was present in 90% of children. The genetic analysis’ results were only available for 20 children. An underlying causative homozygous mutation was detected in 18 children (90%): NPHS1 (9), NPHS2(2), LAMB2(3), PLCE1(1), WT1(1), and ITSN1 novel mutation (2). One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease. All CNS cases were all managed with intermittent intravenous albumin infusion, ACEi, diuretics, and indomethacin. None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources. Only one child achieved partial remission, while 15 children died at a median (range) age of 5.8 (1.25–29) months. The remaining 14 children were followed up for an average of 36 (3.9–120) months. Three children progressed to end-stage kidney disease and PD was performed in only two children.

Conclusions

NPHS1 is the main underlying cause of CNS and INS in our study population. CNS and INS were associated with high morbidity and mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Niaudet P, Mattoo TK, Kim MS. Congenital and infantile nephrotic syndrome. UpToDate. https://www.uptodate.com/contents/congenital-and-infantile-nephrotic-syndrome. Accessed 24 Sept 2018.

  2. Wang JJ, Mao JH. The etiology of congenital nephrotic syndrome: current status and challenges. World J Pediatr. 2016;12:149–58.

    Article  PubMed  Google Scholar 

  3. Berody S, Heidet L, Gribouval O, Harambat J, Niaudet P, Baudouin V, et al. Treatment and outcome of congenital nephrotic syndrome. Nephrol Dial Transpl Nephrol Dial Transplant. 2018. https://doi.org/10.1093/ndt/gfy015.

    Article  Google Scholar 

  4. Schoeb DS, Chernin G, Heeringa SF, Matejas V, Held S, Vega-Warner V, et al. Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS). Nephrol Dial Transpl. 2010;25:2970–6.

    Article  CAS  Google Scholar 

  5. Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008;23:1291–7.

    Article  CAS  PubMed  Google Scholar 

  6. Schumacher V, Scharer K, Wuhl E, Altrogge H, Bonzel KE, Guschmann M, et al. Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations. Kidney Int. 1998;53:1594–600.

    Article  CAS  PubMed  Google Scholar 

  7. Hinkes BG, Mucha B, Vlangos CN, Gbadegesin R, Liu J, Hasselbacher K, et al. 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. 2007;119:e907–19.

    Article  PubMed  Google Scholar 

  8. Chen YM, Kikkawa Y, Miner JH. A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion. J Am Soc Nephrol. 2011;22:849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rahman H, Begum A, Jahan S, Muinuddin G, Hossain MM. Congenital nephrotic syndrome, an uncommon presentation of cytomegalovirus infection. Mymensingh Med J. 2008;17:210–3.

    CAS  PubMed  Google Scholar 

  10. Xiao HJ, Liu JC, Zhong XH. Congenital syphillis presenting congenital nephrotic syndrome in two children and related data review. Beijing Da XueXue Bao Yi Xue Ban. 2011;43:911–3.

    Google Scholar 

  11. Hamed RM, Shomaf M. Congenital nephrotic syndrome: a clinico-pathologic study of thirty children. J Nephrol. 2001;14:104–9.

    CAS  PubMed  Google Scholar 

  12. Work DF, Schwartz GJ. Estimating and measuring glomerular filtration rate in children. Curr Opin Nephrol Hypertens. 2008;17:320–5.

    Article  PubMed  Google Scholar 

  13. Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26:1279–89.

    Article  CAS  PubMed  Google Scholar 

  14. Hameed A, Mir A, Nasir M, Ajmal M. Bioinformatics evaluation of NPHS2 deletion mutation associated with congenital nephrotic syndrome in a consanguineous Pakistani family. Clin Genet. 2015;87:599–601.

    Article  CAS  PubMed  Google Scholar 

  15. Mattoo TK. Genetically transmitted renal diseases in children: a saudi perspective. Saudi J Kidney Dis Transpl. 1998;9:105–9.

    CAS  PubMed  Google Scholar 

  16. Kari JA, Bockenhauer D, Stanescu H, Gari M, Kleta R, Singh AK. Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research. Am J Kidney Dis. 2014;63:304–10.

    Article  PubMed  Google Scholar 

  17. Trautmann A, Lipska-Zietkiewicz BS, Schaefer F. Exploring the clinical and genetic spectrum of steroid resistant nephrotic syndrome: the PodoNet Registry. Front Pediatr. 2018;6:200. 

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kari JA, El-Desoky SM, Gari M, Malik K, Vega-Warner V, Lovric S, et al. Steroid-resistant nephrotic syndrome: impact of genetic testing. Ann Saudi Med. 2013;33:533–8.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Matejas V, Hinkes B, Alkandari F, Al-Gazali L, Annexstad E, Aytac MB, et al. Mutations in the human laminin beta2 (LAMB2) gene and the associated phenotypic spectrum. Hum Mutat. 2010;31:992–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Koziell A, Iyer VK, Moghul NE, Ramani P, Taylor CM. Congenital nephrotic syndrome. Pediatr Nephrol. 2001;16:185–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, et al. Genotype-phenotype associations in WT1 glomerulopathy. Kidney Int. 2014;85:1169–78.

    Article  CAS  PubMed  Google Scholar 

  22. Ashraf S, Kudo H, Rao J, Kikuchi A, Widmeier E, Lawson JA, et al. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nat Commun. 2018;9:60.

    Article  CAS  Google Scholar 

  23. Mario FD, Pofi R, Gigante A, Rivoli L, Rosato E, Isidori AM, et al. Hypothyroidism and nephrotic syndrome: why, when and how to treat. Curr Vasc Pharmacol. 2017;15:398–403.

    Article  CAS  PubMed  Google Scholar 

  24. Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (1). N Engl J Med. 1988;319:1065–72.

    Article  CAS  PubMed  Google Scholar 

  25. Hurley JK. Symptomatic hyponatremia in nephrotic syndrome. Am J Dis Child. 1980;134:204–6.

    CAS  PubMed  Google Scholar 

  26. Kari JA, Montini G, Bockenhauer D, Brennan E, Rees L, Trompeter RS, et al. Clinico-pathological correlations of congenital and infantile nephrotic syndrome over twenty years. Pediatr Nephrol. 2014;29:2173–80.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mahan JD, Mauer SM, Sibley RK, Vernier RL. Congenital nephrotic syndrome: evolution of medical management and results of renal transplantation. J Pediatr. 1984;105:549–57.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr Nawfal Sharief for reviewing and editing the manuscript. We are also grateful to Prof. Friedhelm Hildebrandt and his group at Harvard Medical School for their generous support of performing all the genetics study for free and for giving the permission to use the data in this manuscript.

Funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah. The authors therefore, acknowledge with thanks DSR technical and financial support.

Author information

Authors and Affiliations

  1. King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

    Sara Nawfal Sharief, Nada Abdullatif Hefni, Walaa Ali Alzahrani, Iman Ibrahim Nazer, Marwa Abdullah Bayazeed, Osama Y. Safdar, Sherif M. El-Desoky & Jameela Abdulaziz Kari

  2. College of Medicine, Pediatric Department, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Khalid A. Alhasan

  3. Department of Pediatrics, Faculty of Medicine, Pediatric Nephrology Center of Excellence, King Abdulaziz University, PO Box 80215, Jeddah, 21589, Kingdom of Saudi Arabia

    Osama Y. Safdar, Sherif M. El-Desoky & Jameela Abdulaziz Kari

Authors
  1. Sara Nawfal Sharief
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nada Abdullatif Hefni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walaa Ali Alzahrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iman Ibrahim Nazer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marwa Abdullah Bayazeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Khalid A. Alhasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Osama Y. Safdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sherif M. El-Desoky
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jameela Abdulaziz Kari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SNS: coordination of the study, collection of data, and writing first version of the manuscript. NH: collection of data and writing first version of the manuscript. WA: collection of data and writing first version of the manuscript. IN: collection of data and writing first version of the manuscript. MB: collection of data and writing first version of the manuscript. Khalid A. Alhasan: editing and reviewing. OYS: editing and reviewing. SMED: collection and providing of the data. JAK: idea, supervision, editing, and reviewing.

Corresponding author

Correspondence to Jameela Abdulaziz Kari.

Ethics declarations

Ethical approval

Ethical approval was obtained from the local ethical approval committee of the Faculty of Medicine at King Abdul Aziz University.

Conflict of interest

No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharief, S.N., Hefni, N.A., Alzahrani, W.A. et al. Genetics of congenital and infantile nephrotic syndrome. World J Pediatr 15, 198–203 (2019). https://doi.org/10.1007/s12519-018-00224-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-018-00224-0

Keywords

Search

Navigation