Objective

To explore the clinical characteristics and diagnosis of children with neurofibromatosis type 1（NF1）complicated with nephrotic syndrome（NS），and to investigate the potential association mechanism between NF1 and NS through a literature review.

Methods

A 12-year-old male child with NF1 complicated with NS （Child 1）who was admitted to the Hubei Maternal and Child Health Hospital affiliated to Huazhong University of Science and Technology in February 2021 was selected as the research subject.A retrospective analysis was conducted to collect the clinical data，whole-exome sequencing（WES）results，and Sanger sequencing validation results of child 1.The pathogenicity of the detected variants was analyzed according to the guidelines established by the American College of Medical Genetics and Genomics （ACMG）.Keywords such as"neurofibromatosis type 1""nephrotic syndrome""nephritis"and their English equivalents were used to search relevant literature in databases such as Wanfang Data Service Platform，China National Knowledge Infrastructure （CNKI），and Pub Med.The search period was set from January 1，2001，to December 30，2024.This study adhered to the requirements of the revised 2013 DeclarationofHelsinkiofthe WorldMedicalAssociation.Informed consent was obtained from the guardians of the child.

Results

①Child 1，a boy，was admitted to the pediatric nephrology and rheumatology immunology department of Hubei Maternal and Child Health Hospital on January 14，2021，due to"generalized edema for 2 days".Physical examination upon admission revealed café-au-lait spots over the entire body，multiple small freckles in both axillae，and two tumors approximately 0.5 cm in size in the right renal area.Laboratory tests showed massive proteinuria，hypoalbuminemia，and hyperlipidemia，leading to a diagnosis of NF1 complicated with NS.After admission，the child was treated with adequate glucocorticoids to induce remission，and proteinuria turned negative before discharge.Seven days after discharge，the child again presented with proteinuria without any identifiable cause.Renal biopsy histopathological examination suggested podocyte lesions.Whole-exome sequencing（WES）revealed a deletion mutation （6361-6362del TC）in exon 42 of the NF1 gene on chromosome 17（NM_001042492），causing a frameshift variant，which met the ACMG pathogenicity criteria.Treatment with methylprednisolone tablets combined with tacrolimus was administered，and proteinuria turned negative again before discharge.②Literature review：A total of 17 patients were included，aged 3 to 70 years，with childhood-onset in 5 cases （29.4%）.Ten cases （58.8%）were confirmed to have NF1 through genetic testing.The types of renal injury associated with NF1 included membranous nephropathy，focal segmental glomerulosclerosis （FSGS），and Ig A nephropathy.

Conclusions

NF1 complicated with NS is clinically rare，and genetic testing is crucial for a definitive diagnosis.Abnormalities in the m TOR signaling pathway may mediate podocyte damage，leading to proteinuria.Combined treatment with glucocorticoids and immunosuppressants may be an effective therapeutic approach.