Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations

Abstract

Several genes have been implicated in genetic forms of nephrotic syndrome occurring in children. It is now known that the phenotypes associated with mutations in these genes display significant variability, rendering genetic testing and counselling a more complex task. This review will focus on the recent clinical findings associated with those genes known to be involved in isolated steroid-resistant nephrotic syndrome in children and, thereby, propose an approach for appropriate mutational screening. The recurrence of proteinuria after transplantation in patients with hereditary forms of nephrotic syndrome will also be discussed.

Fig. 1

Genetic approach in children with isolated steroid-resistant nephrotic syndrome. Asterisk In patients with minimal glomerular change/focal segmental glomerulosclerosis (MGC/FSGS) who present in the congenital period, those with nephrotic syndrome (NS) onset very shortly after birth should probably be screened first for NPHS1 mutations followed by NPHS2 mutations. Cross Only nonsyndromic forms of NS associated with WT1 mutations are included. Most of the WT1 mutations in patients with isolated steroid-resistant NS (SRNS) have been found in phenotypically female patients. PT, proximal tubules, DMS diffuse mesangial sclerosis, AR autosomal recessive, AD autosomal dominant