Genetics of congenital and infantile nephrotic syndrome

  • Sara Nawfal Sharief
  • Nada Abdullatif Hefni
  • Walaa Ali Alzahrani
  • Iman Ibrahim Nazer
  • Marwa Abdullah Bayazeed
  • Khalid A. Alhasan
  • Osama Y. Safdar
  • Sherif M. El-Desoky
  • Jameela Abdulaziz KariEmail author
Original Article



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.


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


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.


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


Congenital nephrotic Infantile nephrotic Genetics Outcome 



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.

Author 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.


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.

Compliance with ethical standards

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.


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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  • Sara Nawfal Sharief
    • 1
  • Nada Abdullatif Hefni
    • 1
  • Walaa Ali Alzahrani
    • 1
  • Iman Ibrahim Nazer
    • 1
  • Marwa Abdullah Bayazeed
    • 1
  • Khalid A. Alhasan
    • 2
  • Osama Y. Safdar
    • 1
    • 3
  • Sherif M. El-Desoky
    • 1
    • 3
  • Jameela Abdulaziz Kari
    • 1
    • 3
    Email author
  1. 1.King Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  2. 2.College of Medicine, Pediatric DepartmentKing Saud UniversityRiyadhKingdom of Saudi Arabia
  3. 3.Department of Pediatrics, Faculty of Medicine, Pediatric Nephrology Center of ExcellenceKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia

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