From the Guidelines
Congenital nephrotic syndrome is a group of rare genetic disorders that cause severe protein leakage in the kidneys, with the main types including Finnish-type congenital nephrotic syndrome, Diffuse mesangial sclerosis, Congenital nephrotic syndrome of the French type, Denys-Drash syndrome, and Nail-patella syndrome, as reported in the most recent study by 1. The main types of congenital nephrotic syndrome are:
- Finnish-type congenital nephrotic syndrome (CNF), caused by mutations in the NPHS1 gene encoding nephrin
- Diffuse mesangial sclerosis (DMS), often associated with WT1 gene mutations
- Congenital nephrotic syndrome of the French type, caused by NPHS2 gene mutations affecting podocin
- Denys-Drash syndrome, characterized by WT1 mutations with associated genital abnormalities and Wilms tumor risk
- Nail-patella syndrome, linked to LMX1B gene mutations with skeletal abnormalities These disorders result from genetic mutations affecting podocyte structure and function in the glomerular filtration barrier, leading to massive proteinuria, hypoalbuminemia, edema, and increased susceptibility to infections, as described in the study by 1. The management of congenital nephrotic syndrome typically involves aggressive nutritional support, albumin infusions, diuretics, prophylactic antibiotics, and immunizations, with many cases eventually requiring nephrectomy and dialysis with kidney transplantation as the definitive treatment, as recommended by the study by 1. Early genetic testing is crucial for diagnosis, prognosis, and family counseling, as it enables the identification of the underlying genetic abnormality and informs the management and treatment of the condition, as emphasized in the study by 1. Key aspects of management include:
- Clinical and biological assessment, including screening for congenital infections and genetic analysis
- Initial treatment based on the results of these assessments
- Management by a specialized pediatric nephrology team
- Symptomatic treatments to maintain blood volume and prevent complications
- Follow-up by a multidisciplinary team
- Consideration of nephrectomy for children with persistent, severe congenital nephrotic syndrome despite optimal management.
From the Research
Types of Congenital Nephrotic Syndrome
- Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessively inherited disease characterised by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin 2.
- The NPHS1 gene mutated in NPHS1 children has recently been identified, and the gene codes for nephrin, a cell-surface protein of podocytes 3.
- Two mutations, named Fin-major and Fin-minor, have been found in over 90% of the Finnish patients 3.
- In non-Finnish patients, most mutations found are missense mutations, but they also include nonsense and splice site mutations, as well as deletions and insertions 4.
- A study in Italy found 13 mutations in the NPHS1 gene, including deletions, insertions, nonsense and missense mutations, with seven of these being newly described 5.
Genetic Mutations
- The nephrin gene consists of 29 exons spanning 26 kb in the chromosomal region 19q13.1 6.
- A total of 32 novel mutations, including deletions, insertions, nonsense, missense, and splicing mutations, and two common polymorphisms were found in the NPHS1 gene 6.
- The most common NPHS1 gene mutations, Fin-major and Fin-minor, both lead to an absence of nephrin and podocyte slit diaphragms, as well as a clinically severe form of NPHS1, the Finnish type of congenital nephrotic syndrome 3.
- A mutation update summarizes the nature of all previously reported nephrin mutations and describes 20 novel mutations recently identified 4.