Congenital Nephrotic Syndrome Research Articles

Case report: Unveiling a less severe congenital nephrotic syndrome in a Rapa Nui patient with a NPHS1 Maori founder variant

Case report: Unveiling a less severe congenital nephrotic syndrome in a Rapa Nui patient with a NPHS1 Maori founder variant

Serological responses to immunization during nephrosis in infants with congenital nephrotic syndrome of the Finnish type.

Pretransplant vaccination is generally recommended to solid organ transplant recipients. In infants with congenital nephrotic syndrome (CNS), the immune response is hypothetically inferior to other patients due to young age and urinary loss of immunoglobulins, but data on the immunization response in severely nephrotic children remain scarce. If effective, however, early immunization of infants with CNS would clinically be advantageous. We investigated serological vaccine responses in seven children with CNS who were immunized during nephrosis. Antibody responses to measles-mumps-rubella -vaccine (MMR), a pentavalent DTaP-IPV-Hib -vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b), varicella vaccine, combined hepatitis A and B vaccine, and pneumococcal conjugate vaccine (PCV) were measured after nephrectomy either before or after kidney transplantation. Immunizations were started at a median age of 7 months [interquartile range (IQR) 7-8], with a concurrent median proteinuria of 36,500 mg/L (IQR 30,900-64,250). Bilateral nephrectomy was performed at a median age of 20 months (IQR 14-25), and kidney transplantation 10-88 days after the nephrectomy. Antibody levels were measured at median 18 months (IQR 6-23) after immunization. Protective antibody levels were detected in all examined children for hepatitis B (5/5), Clostridium tetani (7/7), rubella virus (2/2), and mumps virus (1/1); in 5/6 children for varicella; in 4/6 for poliovirus and vaccine-type pneumococcal serotypes; in 4/7 for Haemophilus influenzae type B and Corynebacterium diphtheriae; in 1/2 for measles virus; and in 2/5 for hepatitis A. None of the seven children had protective IgG levels against Bordetella pertussis. Immunization during severe congenital proteinuria resulted in variable serological responses, with both vaccine- and patient-related differences. Nephrosis appears not to be a barrier to successful immunization.

Early diagnosis and management of finish type congenital nephrotic syndrome in a 3-year-old child: A case report

This study describes a 3-year-old non Finnish girl who was diagnosed with Finnish-type nephrotic syndrome (FTNS), a rare kidney illness brought on by NPHS1 gene abnormalities. Even though she had low protein levels and severe swelling when she was three months old, her case of congenital nephrotic syndrome (CNS) was incorrectly identified as minimal change disease (MCD). The standard MCD treatments, cyclosporine and steroids, did not affect her. A genetic test and a kidney sample confirmed the diagnosis of FTNS, a condition that necessitates an early renal transplant for survival. She is awaiting a kidney transplant and was treated with drugs that save proteins to lessen her edema. The study emphasizes the significance of FTNS early and correct diagnosis as well as the requirement for alternate treatments for this difficult illness.

Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. We evaluated obesity and longitudinal growth among children (1-18years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Quantitative phenotyping of Nphs1 knockout mice as a prerequisite for gene replacement studies.

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of chronic kidney disease before the age of 25 yr. Nephrin, encoded by NPHS1, localizes to the slit diaphragm of glomerular podocytes and is the predominant structural component of the glomerular filtration barrier. Biallelic variants in NPHS1 can cause congenital nephrotic syndrome of the Finnish type, for which, to date, no causative therapy is available. Recently, adeno-associated virus (AAV) vectors targeting the glomerular podocyte have been assessed as a means for gene replacement therapy. Here, we established quantitative and reproducible phenotyping of a published, conditional Nphs1 knockout mouse model (Nphs1tm1.1Pgarg/J and Nphs2-Cre+) in preparation for a gene replacement study using AAV vectors. Nphs1 knockout mice (Nphs1fl/fl Nphs2-Cre+) exhibited 1) a median survival rate of 18 days (range: from 9 to 43 days; males: 16.5 days and females: 20 days); 2) an average foot process (FP) density of 1.0 FP/µm compared with 2.0 FP/µm in controls and a mean filtration slit density of 2.64 µm/µm2 compared with 4.36 µm/µm2 in controls; 3) a high number of proximal tubular microcysts; 4) the development of proteinuria within the first week of life as evidenced by urine albumin-to-creatinine ratios; and 5) significantly reduced levels of serum albumin and elevated blood urea nitrogen and creatinine levels. For none of these phenotypes, significant differences between sexes in Nphs1 knockout mice were observed. We quantitatively characterized five different phenotypic features of congenital nephrotic syndrome in Nphs1fl/fl Nphs2-Cre+ mice. Our results will facilitate future gene replacement therapy projects by allowing for sensitive detection of even subtle molecular effects.NEW & NOTEWORTHY To evaluate potential, even subtle molecular, therapeutic effects of gene replacement therapy (GRT) in a mouse model, prior rigorous quantifiable and reproducible disease phenotyping is necessary. Here, we, therefore, describe such a phenotyping effort in nephrin (Nphs1) knockout mice to establish the basis for GRT for congenital nephrotic syndrome. We believe that our findings set an important basis for upcoming/ongoing gene therapy approaches in the field of nephrology, especially for monogenic nephrotic syndrome.

Congenital Nephrotic Syndrome: A Case Report

Congenital nephrotic syndrome (CNS) is a rare disorder characterized by massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema that occurs in the first three months of life. The incidence of CNS is about 1.5% of all cases of nephrotic syndrome in children, while the incidence in children is about 2 per 100,000. The pathogenesis of CNS is thought to be due to genetic defects in the components of the glomerular filtration barrier, particularly nephrin and podocin, which cause most similar cases. A perinatal infection may also cause CNS. The most common type of primary CNS is the Finnish type, inherited in an autosomal recessive manner. We report a case of a six-month-old male patient who presented with swelling of the face, abdomen, and genitals since the age of 3 months, which had worsened a week before admission to the hospital. There was no history of nausea, vomiting, fever, or seizures, and the child could drink milk. Physical examination revealed ascites with positive shifting dullness and pretibial, dorsum pedis, and scrotum edema. The liver and spleen were difficult to assess. Laboratory examination revealed leukocytosis (27.8x103/µL), anemia (7.7 g/dL), thrombocytosis (537x103/μL), hypoalbuminemia (1.5 g/dL), dyslipidemia (total cholesterol 374 mg/dL, HDL 7 mg/dL, LDL 69 mg/dL, triglycerides 1196 mg/dL), proteinuria (+3/300), and hematuria (+3/200). A history of urological ultrasound showed right and left nephropathy with mild hydronephrosis and ascites. To sum up, we reported male patient 6 months with congenital nephrotic syndrome. Chromosomal analysis is recommended in this case.

New insights from the genetic work-up in early onset nephrotic syndrome: report from a registry in western India.

Eighty-five percent of infants with congenital nephrotic syndrome (CNS) and 66% with infantile NS (INS) are likely to have a monogenic etiology. There exists a significant genetic variability between different regions and ethnic groups. This study aimed to determine the genetic defects in children with CNS and INS by establishing a registry in western India. In this cross-sectional study, pediatric nephrologists from 13 private and government institutions shared relevant clinical data and details of the genetic evaluation of children presenting with NS within the first year of life. The median age at presentation was 9months (range 1-23, IQR 3-13months), history of consanguinity between parents existed in 14 patients (34%), family history of similar illness in 6 (15%), and extra-renal manifestations in 17 (41%). Twenty-five (61%) were confirmed to have a monogenic etiology. NPHS1 gene was the most implicated (9/25) followed by PLCE1 (5/25). There were 12 variants of uncertain significance (VUS) involving 10 genes (10/25, 40%), and no definite genetic abnormality was found in 4 (25%). A re-analysis of these VUS attempted 2-3years later facilitated reclassification of 7/12 (58%); increasing the diagnostic yield from 61 to 68.2%. Consistent with worldwide data, variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort. NUP93 and COL4A3 were reported in early onset NS for the first time. Reclassification of VUS should be attempted, if feasible, since it may lead to a useful revision of diagnosis.

Genotype/phenotype relationship in mild congenital nephrotic syndrome

Introduction. Congenital nephrotic syndrome (CNS) is a severe disease complicated by hemodynamic instability, infections, thrombosis, growth disorder and progressive renal failure leading to end-stage kidney disease within a few years. The mutations of NPHS1 encoding nephrin is the most common cause of the CNS. The aim of this paper was to present a patient with NPHS1 homozygous Ser350Pro missense mutation that unexpectedly caused a mild clinical course of CNS. Case outline. We present a female patient who was diagnosed with severe nephrotic syndrome at 2.5 months of age. While waiting for the result of the genetic analysis, she was treated unsuccessfully with corticosteroids and angiotensin converting inhibitor (ACEI) four weeks, and then under Cyclosporine A (CsA) and ACEI she achieved partial remission within three months. Initially, the milder clinical course was explained by the positive effect of CsA, but as partial remission persisted even after the discontinuation of this drug, it remains unclear what influenced the improvement of the clinical course of the disease. At the time of writing this paper, the patient was 10.9 years old with normal serum creatinine, normal blood pressure and non-nephrotic proteinuria. Conclusion. NPHS1 homozygous Ser350Pro missense mutation may be presented by a mild clinical course of CNS. Further studies are needed to clarify a more predictive CNS genotype/phenotype relationship.

Factors associated with early relapses in children with steroid-sensitive nephrotic syndrome.

Objective: To determine different risk factors associated with relapse in children with steroid-sensitive nephrotic syndrome. Study Design: Cross-sectional study. Setting: Department of Pediatric Nephrology, The National Institute of Child Health, Karachi. Period: April 2021 to October 2022. Material &amp; Methods: With a sample size of 170 Children aged 1-12 years of either gender were included in the study by non-probability consecutive sampling. Patients who had congenital nephrotic syndrome previously received immunosuppressive treatment or had any other systemic disease leading to nephrotic syndrome were excluded from the study. Frequencies and percentages were calculated for the quantitative variables while chi-square test was applied for the qualitative variables-value of &lt;0.05 was considered significant. Results: The mean age of the patients was 4.87±2.54 years. The majority of the frequent relapsers (76) were male. The mean serum cholesterol of the patients was 318.71±61.61mg/dl. Of the total sample, 37 (21.76%) were infrequent relapsers and 133 (78.23 %) were frequent relapsers. A significant association was found between upper respiratory tract infection and frequent relapse with a p-value of 0.038. Conclusion: Our study showed a significant association between upper respiratory tract infection and relapse in children with steroid-sensitive nephrotic syndrome.

Renal artery stenosis presenting as congenital nephrotic syndrome with hyponatremic hypertensive syndrome in a 2-month-old infant: a case report

Here, we present the case of a 2-month-old male infant with hyponatremic hypertensive syndrome resulting from stenosis of the right proximal and mid-renal arteries. The patient exhibited nephrotic-range proteinuria, low serum albumin, increased serum creatinine, and elevated renin and aldosterone levels. Doppler ultrasonography and computed tomography angiography revealed decreased vascular flow in the small right renal artery. Following a successful percutaneous balloon angioplasty, the patient experienced a decrease in blood pressure and normalization of serum electrolyte levels within a few days. However, it took 3 months for the proteinuria to resolve completely. This case is significant as it represents the first reported instance of a neonate presenting with clinical features resembling congenital nephrotic syndrome caused by renal artery stenosis that was successfully treated with percutaneous renal angioplasty.

Insight into prevalence, etiology, and modalities of pediatric chronic dialysis: a comprehensive nationwide analysis.

This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.

LAMB2 gene: broad clinical spectrum in Pierson syndrome.

Pierson syndrome (PS) is a rare autosomal recessive disease, characterized by congenital nephrotic syndrome (CNS), and ocular and neurologic abnormalities. In affected cases, there is abnormal b-2 laminin which is compound of the several basement membranes caused by inherited mutations in the LAMB2 gene. Although patients have mutations in the same gene, the phenotype is highly variable. In this case series, the relationship between genotype and phenotype is emphasized, and information about the clinical follow-up of the patients is presented. Hereby, we report four pediatric cases with PS as a result of mutation in the LAMB2 gene. Clinical spectrum of LAMB2-associated disorders varies from mild-to-severe ocular, kidney, and neurologic involvement. Since genotype-phenotype correlation in PS has not been clearly demonstrated, we recommend that all patients with ophthalmic anomalies and glomerular proteinuria should be tested for LAMB2 mutations.

Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20–30% of SRNS patients. Methods: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature. Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel and have not been previously reported in the literature. Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early-onset and extrarenal phenotypes.

Managing hypothyroidism in congenital nephrotic syndrome: A case report

Managing hypothyroidism in congenital nephrotic syndrome: A case report

Genotype-Phenotype Associations in Patients with Congenital and Infantile Nephrotic Syndrome

Genotype-Phenotype Associations in Patients with Congenital and Infantile Nephrotic Syndrome

Efficacy and prognosis of infant kidney transplantation

Objective: To analyze the effect and prognosis of infant kidney transplantation. Methods: Clinical data of 37 cases of infant kidney transplantation under 3 years old in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from June 1, 2017 to July 31, 2022 were retrospectively collected. These 37 cases included 31 primary kidney transplantation and 6 secondary kidney transplantation. Kaplan-Meier method was used to draw the survival curve of the transplanted kidney and the recipient, and the prognosis and complications were analyzed. Median follow-up was 18 months (range: 6-66 months). Results: The recipients were 20 males and 17 females, with a median age of 16 months (range: 2 months, 26 days to 36 months) and a median weight of 8 kg (range: 3.2 to 14.0 kg). The youngest child was only 2 months, 26 days old, and weighed only 3.2 kg. The most common primary disease of recipients was congenital nephrotic syndrome (13 cases, 41.9%). Intra-abdominal transplantation occurred in 19 cases (51.3%) and intra-iliac fossa transplantation occurred in the remaining 18 cases (48.6%). Postoperative renal function recovery was delayed in 7 cases (18.9%), and thrombosis caused renal function loss in 5 cases (13.5%), of which 4 cases received second renal transplantation and were successful. During the follow-up period, there were 11 cases of acute rejection (29.7%) and 6 cases of CMV pneumonia (16.2%). The estimated glomerular filtration rate 1 year after transplantation was higher than that 1 month after surgery [(101.9±22.1) vs (71.1±25.6) ml/(min·1.73m2), P<0.001], and remained constant 2 years after transplantation. Both the 1-year and 2-year survival rates of the transplanted kidney were 85.3%, and both the 1-year and 2-year survival rates of the recipients were 96.8%. Conclusion: Although the implementation of infant kidney transplantation is difficult, it can still achieve relatively satisfactory efficacy and prognosis.

Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome

Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce. We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan. Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G>A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation. The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality.

More than four decades of graft survival in pediatric kidney transplant recipients.

Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40years of graft survival currently alive with a functioning first graft. We reviewed all pediatric (age < 18years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions. We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0years (IQR: 43.1, 48.1)). The median age at transplant was 13.8years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30years, 67.7 (IQR: 63.2, 91.8); and at 40years, 80.3ml/min/1.73 m2 (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease). Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.

Systematic Review of Clinical Characteristics and Genotype-Phenotype Correlation in LAMB2-Associated Disease

Laminin subunit beta-2 (LAMB2)-associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms. In recent years, however, the widespread use of next-generation sequencing (NGS) has helped to discover a variety of phenotypes associated with this disease. Therefore, we conducted this systematic review. A literature search of patients with LAMB2 variants was conducted, and 110 patients were investigated, including 12 of our patients. For genotype-phenotype correlation analyses, the extracted data were investigated for pathogenic variant types, the severity of nephropathy, and extrarenal symptoms. Survival analyses were also performed for the onset age of end-stage kidney disease (ESKD). Among all patients, 81 (78%) presented with congenital nephrotic syndrome, and 52 (55%) developed ESKD within 12 months. The median age at ESKD onset was 6.0 months. Kidney survival analysis showed that patients with biallelic truncating variants had a significantly earlier progression to ESKD than those with other variants (median age 1.2 months vs. 60.0 months, P< 0.05). Although the laminin N-terminal domain is functionally important in laminin proteins, and variants in the laminin N-terminal domain are said to result in a severe kidney phenotype such as earlier onset age and worse prognosis, there were no significant differences in onset age of nephropathy and progression to ESKD between patients with nontruncating variants located in the laminin N-terminal domain and those with variants located outside this domain. This study revealed a diversity of LAMB2-associated diseases, characteristics of LAMB2 nephropathy, and genotype-phenotype correlations.

Genetic analysis and outcomes of Omani children with steroid-resistant nephrotic syndrome.

Nephrotic syndrome (NS) is one of the most common kidney disorders seen by pediatric nephrologists and is defined by the presence of heavy proteinuria (>3.5 g/24 h), hypoalbuminemia (<3.5 g/dL), edema, and hyperlipidemia. Most children with NS are steroid-responsive and have a good prognosis following treatment with prednisolone. However, 10%-20% of them have steroid-resistant nephrotic syndrome (SRNS) and fail to respond to treatment. A significant proportion of these children progress to kidney failure. This retrospective study aimed to determine the underlying genetic causes of SRNS among Omani children below 13 years old, over a 15-year period and included 77 children from 50 different families. We used targeted Sanger sequencing combined with next-generation sequencing approaches to perform molecular diagnostics. We found a high rate of underlying genetic causes of SRNS in 61 (79.2%) children with pathogenic variants in the associated genes. Most of these genetically solved SRNS patients were born to consanguineous parents and variants were in the homozygous state. Pathogenic variants in NPHS2 were the most common cause of SRNS in our study seen in 37 (48.05%) cases. Pathogenic variants in NPHS1 were also seen in 16 cases, especially in infants with congenital nephrotic syndrome (CNS). Other genetic causes identified included pathogenic variants in LAMB2, PLCE1, MYO1E, and NUP93. NPHS2 and NPHS1 genetic variants were the most common inherited causes of SRNS in Omani children. However, patients with variants in several other SRNS causative genes were also identified. We recommend screening for all genes responsible for SRNS in all children who present with this phenotype, which will assist in clinical management decisions and genetic counseling for the affected families.