Familial nephrotic syndrome

Systematic pedigree information was obtained from 70 patients with idiopathic nephrotic syndrome; 16 patients were found to have familial nephrotic syndrome including 1 pair of affected monozygotic twins, 5 affected sibling pairs, 2 affected first cousins from a consanguineous family and 2 patients with sporadic cases from consanguineous families.Patients with familial and sporadic forms of the disease were compared by applying both clinical and histopathologic criteria. No significant differences were found between these groups, but both had a preponderance of males.In contrast to previous reports, the clinical course in the affected monozygotic twins was quite different, providing evidence for the importance of environmental influences on the course of this disease. Furthermore, in affected relatives neither the clinical course nor histopathologic classification was necessarily similar.The recurrence risk for siblings of patients with idiopathic nephrotic syndrome was 0.06. Several possible modes of inheritance were considered. Segregation analysis permitted the exclusion of simple recessive inheritance. The invariable concordance for the occurrence of nephrotic syndrome in both members of monozygotic twinships as well as the sex ratio renders a mixed model, with a small proportion of high risk recessive cases, equally unlikely. The available data are most consistent with a polygenic model which assumes a continuous distribution of disease liability with a discreet threshold effect.