From the Guidelines
Congenital nephrotic syndrome is associated with several genetic syndromes, including Finnish-type congenital nephrotic syndrome, Denys-Drash syndrome, Frasier syndrome, Nail-patella syndrome, Pierson syndrome, and Schimke immuno-osseous dysplasia, which are caused by mutations in genes such as NPHS1, WT1, LMX1B, LAMB2, and SMARCAL1 1.
Genetic Syndromes Associated with Congenital Nephrotic Syndrome
The most common genetic syndromes associated with congenital nephrotic syndrome are:
- Finnish-type congenital nephrotic syndrome, caused by mutations in the NPHS1 gene encoding nephrin
- Denys-Drash syndrome, which involves WT1 gene mutations and presents with nephrotic syndrome, male pseudohermaphroditism, and Wilms tumor
- Frasier syndrome, also caused by WT1 mutations, features nephrotic syndrome, gonadal dysgenesis, and risk of gonadoblastoma
- Nail-patella syndrome, caused by LMX1B mutations, presents with nephrotic syndrome alongside skeletal abnormalities
- Pierson syndrome, which involves LAMB2 mutations and features congenital nephrotic syndrome with ocular abnormalities
- Schimke immuno-osseous dysplasia, caused by SMARCAL1 mutations, presents with nephrotic syndrome, growth retardation, and immune deficiency
Importance of Early Diagnosis
Early diagnosis of these syndromes is crucial for management, which may include supportive care, dialysis, transplantation, and genetic counseling for families 1. The underlying genetic mutations affect podocyte structure and function, disrupting the glomerular filtration barrier and causing protein leakage into urine.
Genetic Testing
Genetic testing is recommended as a first-line diagnostic measure in every patient with congenital nephrotic syndrome, with massively parallel sequencing being the method of choice 1. The minimum set of genes to be tested should include NPHS1, NPHS2, WT1, PLCE1, and LAMB2. Screening of these genes identifies underlying genetic abnormalities in >80% of patients with congenital nephrotic syndrome 1.
From the Research
Syndromes Associated with Congenital Nephrotic Syndrome
- Congenital nephrotic syndrome of the Finnish type (CNF) is a rare and severe disease, characterized by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin 2.
- Denys-Drash syndrome (DDS) is another syndrome associated with congenital nephrotic syndrome, which has a poor renal and life outcome 3.
- The clinical manifestations of CNF and DDS at onset are different, with DDS having a higher serum creatinine level and a larger placenta/fetal weight ratio 3.
- The prognosis for patients with DDS is satisfactory if appropriate and active management is performed, while CNF has a poorer prognosis with a high mortality rate if left untreated 3, 4.
- Other syndromes associated with congenital nephrotic syndrome include: