Clinical and genetic evaluation of familial steroid-responsive nephrotic syndrome in childhood

Steroid-responsive idiopathic nephrotic syndrome (SSINS) is the most common form of nephrotic syndrome in childhood. This article reports a cohort of familial SSINS with disease onset in childhood. The clinical course in term s of age at onset, symptoms during the initial phase, renal morphology, and outcome was evaluated. Furthermore, linkage to NPHS2, the gene for autosom al-recessive steroid-resistant INS on chromosome 1, was examined. Two famil ies with haplotypes consistent with linkage to NPHS2 were evaluated for mut ations in the NPHS2 gene. Familial SSINS (32 patients from 15 familes, mini mal change NS in 12 of 12 biopsies) was found to be a clinically homogeneou s entity. Interfamilial and intrafamilial variability with respect to the a ge at disease onset was low, indicating a strong genetic influence on disea se onset. By linkage studies and mutational analysis, familial SSINS was fo und to be genetically distinct from NPHS2. This is the first report of a la rge cohort of familial SSINS. Exclusion of linkage to NPHS2 makes likely th e existence of a distinct gene locus for SSINS.