Nephrotic syndrome is one of the most common kidney diseases in pediatrics, as well as one of the most common diagnoses in children who receive dialysis. It is a heterogeneous kidney disease characterized by an increase in the permeability of glomerular capillaries that produces a set of manifestations including proteinuria, hypoalbuminemia, hyperlipidemia, and edema.
Genetic nephrotic syndrome is defined by the presence of pathogenic genetic variants in patients with corticoid-resistant nephrotic syndrome (CRNS), which is generally severe and develops early in life, though it may present at any age. Genetic testing should be considered if there is a family history of corticoid-resistant nephrotic syndrome, in both infantile or congenital (age <1 year) cases, in cases with onset before age 25, poor response to immunosuppressive agents, histological findings of idiopathic focal segmental glomerulosclerosis or idiopathic diffuse mesangial sclerosis in renal biopsy, extrarenal (syndromic) manifestations, and/or kidney failure. A genetic test may help determine the expected clinical progression of the disease, such as the potential response to drugs, the rate of progression to terminal kidney failure, and the risk of post-transplantation relapse.
Over 40 monogenetic causes have been identified, which affect the glomerular barrier, slit diaphragm proteins, the actin cytoskeleton, some mitochondrial proteins, adhesion proteins, and proteins of the glomerular basement membrane, as well as some nuclear transcription factors, among others. A genetic test is recommended for all children who present nephrotic syndrome in their first year of life, in children with corticoid-resistant nephrotic syndrome associated with malformations or other syndromes, and in children with a family history of nephrotic syndrome or progressive kidney disease.
