Is there a genetic contribution to nephrotic syndrome?
Approximately 5% of cases of MCNS occur in a familial pattern with parent-child or sibling-sibling clusters.
However, there are little data about the frequency of causative genetic mutations in steroid-responsive disease. In nearly 30% to 40% of cases of primary FSGS, genetic mutations in podocyte proteins have been identified.
The most commonly affected protein is podocin, detected in up to 20% of sporadic and familial cases.
Other proteins linked to FSGS include α-actinin-4, CD2AP, Wilms tumor-1 (Denys-Drash syndrome), phospholipase C epsilon1, TRPC6, and the inverse formin gene INF2.
Defects in the nephrin gene and laminin β2 (Pierson syndrome) are associated with congenital nephrotic syndrome and disease in the first year of life. Recently, mutations in mitochondrial and nuclear transport proteins have been associated with FSGS.
The list of genetic causes of nephrotic syndrome, and FSGS in particular, is likely to grow over time. However, the exact frequency remains to be determined as methods to distinguish disease-causing genetic mutations from normal variants are refined.
MN has been linked to various HLA polymorphisms. MPGN type II (DDD) is associated with a variety of genetic mutations in proteins involved in the alternative pathway of complement.
Currently, the role of genetic testing in patients with new-onset nephrotic syndrome that is resistant to corticosteroids is subject to ongoing debate.
Patients with nephrotic syndrome who have a genetic basis for the disease may have not only a lower response rate to immunosuppressive therapy but also a lower risk of recurrent disease following transplantation.
