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Congenital Nephrotic Syndrome

Last updated May 20, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Congenital Nephrotic Syndrome is rare disorder affecting infants at birth or within 1-3 months of birth. The condition is caused by a genetic defect in the protein nephrin, which is an important component of the kidney filtration system.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Congenital Nephrotic Syndrome NOS (Disorder)
  • Familial Nephrotic Syndrome
  • Finnish Congenital Nephrosis

What is Congenital Nephrotic Syndrome? (Definition/Background Information)

  • Congenital Nephrotic Syndrome is rare disorder affecting infants at birth or within 1-3 months of birth. The condition is caused by a genetic defect in the protein nephrin, which is an important component of the kidney filtration system
  • Due to this defect, substantial amounts of protein and fat are excreted in urine, resulting in swelling of the body and causing critical kidney-related complications
  • Congenital Nephrotic Syndrome is caused by genetic mutation(s); at least 4 genes, namely, NPHS1, NPHS2, WT1, and LAMB2, are known to be involved. Although the syndrome can occur worldwide, people of Finnish descent are more at risk for developing the condition
  • The disorder results in low birth weight, foamy urine, swelling of the body, and cough in the newborn. These symptoms form the basis of diagnosis of Congenital Nephrotic Syndrome along with urine and blood tests
  • The treatment is symptomatic and may involve dialysis. Without adequate treatment, the condition may lead to complications such as infections, kidney failure, and end-stage renal disease
  • The outcome is poor in most cases and many children succumb to the condition within 5 years of birth. A successful kidney transplantation performed during the early years may help prolong life

Who gets Congenital Nephrotic Syndrome? (Age and Sex Distribution)

  • Congenital Nephrotic Syndrome is an inherited genetic disorder affecting newborn babies and neonates (1 to 28 day old) at a frequency of 1:100,000
  • The manifestation of the condition may begin at or soon after birth
  • Both male and female babies are equally affected by this disorder
  • The condition is reported worldwide, although individuals of Finnish origin are more prone to the disorder, with an incidence frequency of 1:10,000

What are the Risk Factors for Congenital Nephrotic Syndrome? (Predisposing Factors)

Congenital Nephrotic Syndrome is an inherited disorder and the following are some known risk factors:

  • A family history of the disorder
  • Being of Finnish descent

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Congenital Nephrotic Syndrome? (Etiology)

Congenital Nephrotic Syndrome is caused by mutation(s) in any of the NPHS1, NPHS2, WT1, or LAMB2 genes. The condition may be inherited in an autosomal dominant or autosomal recessive manner.

  • Of the 4 causative genes, NPHS1 and NPHS2 mutations are more commonly observed:
    • Under normal circumstances, the NPHS1 and NPHS2 genes code for proteins known as nephrins. These proteins localize to the surface of cells called podocytes, within the glomeruli of the kidneys (the filtration units of a kidney)
    • The proteins transmit signals and regulate the filtration of blood in the area known as the slit diaphragm, between podocytes
    • A properly functioning slit diaphragm retains important proteins from blood, while excreting salt and sugar into urine
    • A mutation in either gene can cause dysfunctional or absent nephrin protein. This leads to abnormal slit diaphragm formation, and a consequent malfunction of the structure. The abnormal slit diaphragm does not filter protein properly, allowing it to be excreted in urine, causing the symptoms of the disorder
    • Mutations in the NPHS1 gene are reported to cause all cases of the syndrome in Finnish population. NPHS2 gene mutations cause most other cases of Congenital Nephrotic Syndrome
    • The disorder is inherited in an autosomal recessive manner
  • Mutations in the WT1 gene cause fewer cases of Congenital Nephrotic Syndrome. The WTI gene codes for a transcription factor known as Wilm’s tumor 1 protein, that binds both RNA and DNA. The absence of this protein may cause collapsed glomeruli
    • The types of Congenital Nephrotic Syndrome caused by this mutation are also known as Denys-Drash and Frasier syndromes
    • Mutation(s) in the WT1 gene are inherited in an autosomal dominant manner. An affected individual inherits the defective gene copy from one parent
  • LAMB2 gene codes for laminin-β2, which is localized in the basal membrane of glomeruli, and plays a role in type IV collagen assembly
    • The type of Congneital Nephrotic Syndrome caused by this mutation is also known as Pierson syndrome
    • The mutation(s) in LAMB2 affect the sensitivity and permeability of glomerular membrane
    • This mutation, which is similar to NPHS1 and NPHS2 mutations, is inherited in an autosomal recessive pattern
  • Multigene mutations in NPHS1, NPHS2, and WT1 genes, causing Congenital Nephrotic Syndrome are also reported

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Congenital Nephrotic Syndrome?

The signs and symptoms of Congenital Nephrotic Syndrome may include:

  • Low birth weight
  • Decreased urination
  • Foamy urine
  • Cough (in newborns)
  • Generalized edema due to fluid in the body (swelling of the whole body)
  • Poor appetite

The signs and symptoms of the disorder may be worsened with microbial infections (such as syphilis, toxoplasmosis, and cytomegalovirus infections) affecting the baby during the fetal stage.

How is Congenital Nephrotic Syndrome Diagnosed?

The diagnosis of Congenital Nephrotic Disorder may be made before birth (prenatal) or immediately following birth. The following are some diagnostic methods employed:

  • Prenatal diagnosis:
    • Test for the levels of alpha-fetoprotein in the amniotic fluid: If a positive test result is obtained, then genetic test is required to confirm the disorder
    • Ultrasound scans to check the size of placenta, which is typically larger than normal if the baby has the syndrome
    • Molecular genetic testing for gene mutations, if available
  • Tests and exams performed following birth of the child:
    • Complete physical examination and assessment of symptoms
    • Evaluation of family medical history
    • Blood test to check for total protein levels: Reduced levels may be indicative of the condition, which is due to high excretion of protein from the body
    • Urine analysis for the presence of proteins and fats

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Congenital Nephrotic Syndrome?

Certain complications may develop because of prolonged kidney malfunction in Congenital Nephrotic Syndrome, and these may include:

  • Acute kidney failure
  • Blood clots
  • Malnutrition
  • Anemia
  • Severe and chronic kidney failure
  • End-stage kidney disease
  • Cardiovascular defects and abnormalities

How is Congenital Nephrotic Syndrome Treated?

The treatment measures for Congenital Nephrotic Syndrome are focused on addressing the most critical of problems and are often undertaken urgently, by a team of healthcare professionals. The following are some treatment methods:

  • Limiting fluid intake
  • Use of medications, such as ACE inhibitors, to block loss of proteins in urine
  • Use of non-steroidal anti-inflammatory medicines (NSAIDs), to reduce loss of protein in urine
  • Water pills or diuretics to remove excess body fluid and reduce edema
  • In case of any secondary bacterial infections, antibiotics are administered
  • Modifications to the diet, recommendation of dietary supplements (to compensate for all the lost minerals and vitamins), etc. may avert malnourishment and other potential health conditions
  • Since the kidney filtration system is affected and causes excessive protein excretion, often the removal of both kidneys helps arrest protein loss. However, this procedure must be immediately followed by a kidney transplantation
  • During this period, dialysis is used as an interim support for lost kidney function

How can Congenital Nephrotic Syndrome be Prevented?

  • Congenital Nephrotic Syndrome is a genetic disorder, and therefore, no guidelines or methods currently exist for its prevention
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Congenital Nephrotic Syndrome

What is the Prognosis of Congenital Nephrotic Syndrome? (Outcomes/Resolutions)

Congenital Nephrotic Syndrome is often a fatal genetic disorder with poor prognosis.

  • Most infants succumb to the condition within the first year after birth or before they reach age 5 years
  • In some cases, it may be possible to manage the condition with timely, aggressive, and active treatment, often with kidney transplantation early in the child’s life

Additional and Relevant Useful Information for Congenital Nephrotic Syndrome:

  • Both kidneys are severely affected in children with Congenital Nephrotic Syndrome, with a loss of function. The kidneys cannot be medically treated to complete recovery, since the cause is a genetic abnormality. In order to save a child with this genetic disorder, a kidney transplantation at the earliest possible time may be necessary
  • Congenital Nephrotic Syndrome is also known by the following synonyms:
    • Congenital Nephrosis 1, Finnish Type
    • Congenital Nephrotic Syndrome NOS (Disorder)
    • Congenital Nephrotic Syndrome of the Finnish Type (CNF)
    • Finnish Congenital Nephrosis

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: June 6, 2017
Last updated: May 20, 2018