2024 Volume 37 Pages 135-140
WT1 mutations present a diverse clinical picture, including nephropathy, urogenital abnormalities and Wilms tumors. In recent years, the genotype–phenotype association has become clearer. Among patients with severe proteinuria due to single gene mutations in Japan, WT1 is the most common causative gene. Missense mutations cause early onset of nephropathy as congenital nephrotic syndrome or infantile nephrotic syndrome due to dominant-negative effects and rapidly progress to kidney failure, whereas truncating mutations and KTS-splicing mutation are characterized by relatively slow onset of nephropathy and progression to kidney failure. Pediatric nephrologists, who often play a central role in the overall management of patients, are required to have knowledge not only in the management of nephropathy but also in addressing extrarenal complications. These include the need and timing of prophylactic nephrectomy and gonadectomy, endocrine management, resistant hypertension, prolonged hypotension after nephrectomy, and rare complications such as diaphragmatic communication. It is essential to understand the flow of care for patients with WT1 gene mutations.
