Congenital nephrotic syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 5, 2016
StartDiseasesCongenital nephrotic syndrome

Congenital nephrotic syndrome is a rare congenital disorder that affects the kidneys in infants. It causes swelling, protein in the urine (proteinuria), and typically leads to kidney failure in childhood.


Definition & Facts

The condition occurs most often in infants who are Finnish. Finnish infants develop the condition at a rate of one per 10,000 children. The condition is relatively rare in other parts of the world and affects one to three per 100,000 children. Though the term, congenital typically indicates that the condition is present at birth, it may appear within the first three months of life.

The condition causes protein and fat to be excreted in the urine. Protein helps keep water in the bloodstream. When it is excreted through urination, water is prevented from remaining in the bloodstream and enters the tissues in the body. The failing kidneys are not able to excrete the excess water through urine, which causes noticeable swelling to occur.

Symptoms & Complaints

Infants with congenital nephrotic syndrome typically are born with a low birth weight. An abnormally large placenta may also be present during birth. Food allergies or intolerances often appear early in life.

After birth, the infant may have a low appetite but continue to gain weight due to the swelling. Swelling will occur all over the body, with the majority of swelling occurring in the abdominal and facial areas.

When the infant's leg or arm is pressed, an indentation will be left for several moments because of the swelling. The abdominal swelling may cause pain, irritating the infant when touched.

The excess protein in the urine will cause the urine to have a foamy appearance. The infant will only pass a small amount of urine. The urine that is passed will have a dark yellow appearance because it is extremely concentrated.

The infant will have dull hair, pale nail beds and ear cartilage that is less firm than other children's. White blood cells are often reduced due to the syndrome, which causes a weakened immune system. A weakened immune system increases the likelihood that an infant will contract an illness.


The condition is caused by a genetic mutation on the genes, NPHS1 or NPHS2. These genes are responsible for making a kidney protein called nephrin. Nephrin is found in the cells that make up specialized kidney structures called glomeruli. Glomeruli are small capillaries that filter proteins and toxins in the blood and help to produce urine.

Without nephrin, the glomeruli don't work properly. This causes excess protein to exit the body, which in turn causes the swelling. The genes NPHS1 and NPHS2 are autosomal recessive genes.

In order to develop the condition, both parents, who are genetic carriers of the mutated gene, must give a copy to their child. Though the parents won't present with the condition themselves, the copy will pass on to their child and cause the condition to develop. Parents who are both carriers have a 25 percent chance of passing on the genes to their children.

Approximately 15 to 20 percent of infants diagnosed with congenital nephrotic syndrome do not have a genetic mutation. In these infants, it is believed that the condition is caused by an infection, such as congenital syphilis or toxoplasmosis. Mutations in other unidentified genes may also cause the condition to form.

Diagnosis & Tests

During the physical examination by a pediatrician, swelling will be present. The infant's blood pressure may be high (hypertension) due to the swelling and there will be signs of malnutrition due to the infant's loss of appetite. The pediatrician may note abnormal sounds in the heart, lungs, and kidneys. The pediatrician will order several tests. These will include:

  • Urinalysis, which will look for the presence of protein in the urine, blood in the urine (hematuria), and fat in the urine.
  • Blood tests, which will test kidney function, look for the presence of the protein albumin, check the total cholesterol level and look of the levels of different blood cells. Infants will congenital nephrotic syndrome typically present with low levels of red blood cells and white blood cells.
  • Renal ultrasound, which will use sound waves to form an image of the kidneys. This type of ultrasound is non-invasive and will look for any other problems that could be causing kidney dysfunction, such as a kidney cyst, kidney tumor, kidney stone, or renal obstruction.
  • Renal biopsy, which consists of a small amount of kidney tissue being removed with a fine needle. This tissue will be looked at under a microscope to look for signs of congenital nephrotic syndrome or other kidney diseases.

Treatment & Therapy

The infant will require immediate and aggressive treatment. Medications called diuretics will be given to the infant to remove excess fluid from its body. Blood pressure medications called ACE inhibitors will also be prescribed to stop the kidneys from excreting protein in the urine. Antibiotics may also be prescribed to the infant if an infection is present.

The infant will have a central venous catheter surgically put in place in the chest or groin. This catheter will allow daily infusions of albumin in the infant's body to replace the protein that was lost. The pediatrician may recommend that the infant be placed on a special low-sodium diet to prevent the kidneys from being overtaxed.

Nutritional supplements may be given to infants who are suffering from malnutrition or who have low levels or iron. During end-stage renal disease, the child will have to have to undergo dialysis and eventually a kidney transplant.

Prevention & Prophylaxis

Because the syndrome is caused by a genetic mutation, there is nothing that can be done to prevent congenital nephrotic syndrome. Pregnant women who are known to be carriers can have their fetus screened for the disorder by testing the amniotic fluid for elevated levels of alpha-fetoprotein.

If the test is positive, the infant can receive aggressive treatment right at birth. Though most children will enter end-stage renal failure between the ages of two and eight, aggressive treatment may make it possible to delay kidney failure until adolescence or adulthood.