Clinical Featuers And Genotype Of Pediatric Hereditary Nephrotic Syndrome In A Monocentric Study

Objective: To analyze the clinical manifestations,renal pathology,genotype and prognosis of children with hereditary nephrotic syndrome to provide references for the diagnosis and treatment of children with hereditary nephrotic syndrome.Methods: The clinical manifestations,laboratory findings,renal pathological changes,genetic test results and prognosis of 15 children diagnosed with hereditary nephrotic syndrome from 2015.01 to 2019.10 in the Children's Hospital of Chongqing Medical University were analyzed retrospectively.Results: The median age of onset of 15 children with hereditary nephrotic syndrome was 1.17(0.11,5.23)years old,11 children developed edema at the time of onset,the clinical classification was mainly nephritic type nephrotic syndrome.Extrarenal presentations occurred in 8 children and neurological involvement was common.Five children underwent renal pathological examination,which showed focal segmental glomerulosclerosis in 3 cases and minimal change disease in 2 cases.Steroid therapy was not effective in 3 children while steroid combined immunosuppressive therapy had no obvious effect in 5 children.Only 1patient was relieved after the treatment with calcineurin inhibitors.Theoverall prognosis was poor,3 patients developed end-stage renal disease and 3 died during the follow-up period.The median renal survival time was30 months.Hypertension at the onset was associated with poor prognosis.There were 6 cases of autosomal dominant inheritance and 9 cases of autosomal recessive inheritance.Only 1 patient had a family history of nephropathy.Detection of pathogenic genes: 6 cases of WT1,3 cases of NPHS1,2 cases of NPHS2,2 cases of ADCK4,1 case of HADHB and 1case of CRB2.A total of 24 different gene mutations were found including13 missense mutations,5 nonsense mutations,3 splice mutations,3frameshift mutations.12 mutations had no previous reports.24 gene mutations were predicted by bioinformatics softwares,results showed 22 mutations were pathogenic.In WT1 related nephrotic syndrome,missense mutations in exon 9 were associated with Denys-Drash syndrome and KTS mutations in intron 9 were associated with Frasier syndrome.Conclusion: The common pathogenic genes of children with hereditary nephrotic syndrome in our center were WT1,NPHS1,NPHS2 and ADCK4.The clinical characteristics of hereditary nephrotic syndrome caused by different genes are quite different.The phenotype of WT1 related nephrotic syndrome is relevant to the type and location of mutations.Children with hereditary nephrotic syndrome have a poor prognosis.Performing genetic testing in time to find genetic causes can help individualized treatment and prognosis prediction.