Clinical and Genetic Evaluation of Familial Steroid-Responsive Nephrotic Syndrome in Childhood

Abstract

Abstract. 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 terms of age at onset, symptoms during the initial phase, renal morphology, and outcome was evaluated. Furthermore, linkage toNPHS2, the gene for autosomal-recessive steroid-resistant INS on chromosome 1, was examined. Two families with haplotypes consistent with linkage toNPHS2were evaluated for mutations in theNPHS2gene. Familial SSINS (32 patients from 15 families, minimal change NS in 12 of 12 biopsies) was found to be a clinically homogeneous entity. Interfamilial and intrafamilial variability with respect to the age at disease onset was low, indicating a strong genetic influence on disease onset. By linkage studies and mutational analysis, familial SSINS was found to be genetically distinct fromNPHS2. This is the first report of a large cohort of familial SSINS. Exclusion of linkage toNPHS2makes likely the existence of a distinct gene locus for SSINS.