Congenital nephrotic syndrome (CNS), defined as heavy proteinuria, hypoalbuminemia, hyperlipidemia and edema presenting in the first 0-3 months of life, may be caused by congenital syphilis, toxoplasmosis, or congenital viral infections (such as cytomegalovirus). However, the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular filtration barrier in the kidneys. Since 1998, an increasing number of genetic defects have been identified for their involvements in the pathogenesis of CNS, including NPHS1, NPHS2, WT1, PLCE1, and LAMB2.
We searched databases such as PubMed, Elsevier and Wanfang with the following key words: congenital nephrotic syndrome, proteinuria, infants, neonate, congenital infection, mechanism and treatment; and we selected those publications written in English that we judged to be relevant to the topic of this review.
Based on the data present in the literature, we reviewed the following topics: 1) Infection associated CNS including congenital syphilis, congenital toxoplasmosis, and congenital cytomegalovirus infection; 2) genetic CNS including mutation of NPHS1 (Nephrin), NPHS2 (Podocin), WT1, LAMB2 (Laminin-β2), PLCE1 (NPHS3); 3) Other forms of CNS including maternal systemic lupus erythematosus, mercury poisoning, renal vein thrombosis, neonatal alloimmunization against neutral endopeptidase.
At present, the main challenge in CNS is to identify the cause of disease for individual patients. To make a definitive diagnosis, with the exclusion of infection-related CNS and maternal-associated disorders, pathology, family history, inheritance mode, and other accompanying congenital malformations are sometimes, but not always, useful indicators for diagnosing genetic CNS. Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients, however, there are still some challenges with next-generation sequencing that need to be resolved in the future.