A case report of WT1-associated infantile steroid-resistant nephrotic syndrome with atypical genotype–phenotype correlation

Abstract

Infantile nephrotic syndrome (INS) has a slower progression to end-stage kidney disease (ESKD) than congenital nephrotic syndrome (CNS). The genetic variants are non-Finnish-type related; Denys-Drash syndrome (DDS) is the most frequent syndromic disease, characterized by a first-year onset of steroid-resistant nephrotic syndrome, disorder of sex development, predisposition to Wilms tumor, and diffuse mesangial sclerosis (DMS) in kidney biopsy. We report a previously healthy male infant with steroid-resistant nephrotic syndrome (SRNS), cryptorchidism, focal and segmental glomerular sclerosis (FSGS) with pseudo-cystic dilation of proximal tubules, initially interpreted as a genetic, non-syndromic nephrotic syndrome. A WT1 missense likely pathogenic variant was identified, then classified as incomplete Denys-Drash syndrome. We describe the phenotype of an unusual variant. The phenotypic heterogeneity of WT1-associated nephropathy can lead to a misdiagnosis, highlighting the importance of genetic testing in INS to achieve a correct diagnosis and provide the best treatment and surveillance according to the identified genetic variant.