What Is Congenital Nephrotic Syndrome?

Congenital nephrotic syndrome (CNS) consists of a group of diseases. The main clinical feature is the appearance of nephrotic syndrome (large proteinuria, hypoalbuminemia, severe edema, and hyperlipidemia) after birth (within three months). Disease). The onset and severity of nephrotic syndrome vary widely among different diseases.

Basic Information

English name

congenital nephrotic syndrome

Visiting department

Nephrology

Common causes

Caused by genetic mutations, intrauterine infections, or maternal diseases

Common symptoms

Massive proteinuria, hypoproteinemia, severe edema, and hyperlipidemia

Causes of congenital nephrotic syndrome

According to the etiology of congenital nephrotic syndrome, it can be divided into primary (hereditary) and secondary (non-hereditary). The primary cause is usually caused by genetic mutation, and the secondary cause is usually caused by intrauterine infection or maternal disease.

Clinical manifestations and treatment of congenital nephrotic syndrome

1. Congenital nephrotic syndrome Finnish type

The disease-causing gene is NPHS1 (19q13.1), encoding nephrin is an important part of the fissure membrane between the foot processes of glomerular epithelial cells. In Finland, 94% of NPHS1 gene mutations are Fin-major and Fin-minor. These two mutations can cause nephrin expression to be deleted, causing severe clinical symptoms. After receiving kidney transplantation in children with these two mutations, 20% will produce antibodies to nephrin, and a large amount of proteinuria will reappear.

It is an autosomal recessive, most common in the Finnish population and rare in Asians. Symptoms appear in the womb, the newborn is low in weight, severe nephrotic syndrome occurs shortly after birth, rapidly develops into glomerulosclerosis, hormones and immunosuppressants are ineffective, and newborns die within 6 months after delivery Due to serious complications.

Clinical symptoms are typically easy to identify, and can also be distinguished from other neonatal nephrotic syndromes by genetic diagnosis. Adequate supportive care can prolong life, but progress to end-stage renal failure between the ages of 3 and 8 years. The only effective treatment is kidney transplant.

2. Congenital Nephrotic Syndrome-Autosomal Recessive Hormone Resistance

The currently recognized disease-causing gene is NPHS2 (1q25-32), which encodes podocin and forms a fissure membrane with Nephrin.

Nephrotic syndrome occurs most often between 3 months and 5 years of age, with minimal pathological changes in the early stages of renal pathology, followed by focal segmental glomerulosclerosis. Steroid hormone therapy is ineffective. After the onset of symptoms, it quickly progresses to end-stage renal failure, which requires kidney replacement therapy. Rarely recurrence after transplantation. Podocin mutation screening should be performed on children with this type of clinical characteristics to avoid overtreatment.

3. Denys-Drash syndrome (DDS)

Congenital nephrotic syndrome with male pseudohermaphroditism (XY) and Wilms' tumor, and babies with female phenotype with DDS have also been reported. The syndrome is related to mutations in the WT1 (11p13) gene. The patients are almost all heterozygous. The WT1 gene is located in a gene that encodes a transcription factor that plays a key role in the development of the kidney and gonads. Symptoms of the kidney usually occur after birth or within a few months, and the characteristic change is sclerosis of the mesangial area. So far, kidney transplantation is the only effective treatment.