Congenital nephrotic syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Congenital nephrotic syndrome is a kidney condition that begins in infancy and typically leads to irreversible kidney failure (end-stage renal disease) by early childhood. Children with congenital nephrotic syndrome begin to have symptoms of the condition between birth and 3 months.

The features of congenital nephrotic syndrome are caused by failure of the kidneys to filter waste products from the blood and remove them in urine. Signs and symptoms of this condition are excessive protein in the urine (proteinuria), increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells (anemia) in the body, abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with congenital nephrotic syndrome.

Children with congenital nephrotic syndrome typically develop end-stage renal disease between ages 2 and 8, although with treatment, some may not have kidney failure until adolescence or early adulthood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the NPHS1 or NPHS2 gene cause most cases of congenital nephrotic syndrome. These genes provide instructions for making proteins that are found in the kidneys. Specifically, the proteins produced from the NPHS1 and NPHS2 genes are found in cells called podocytes, which are located in specialized kidney structures, called glomeruli, that filter the blood. The proteins are found at the podocyte cell surface in the area between two podocytes called the slit diaphragm. The slit diaphragm is known as a filtration barrier because it captures proteins from blood so that they remain in the body while allowing other molecules like sugars and salts to be excreted in urine. The proteins produced from the NPHS1 and NPHS2 genes also help relay cell signals.

Mutations in the NPHS1 or NPHS2 gene result in a decrease or absence of functional protein, which impairs the formation of normal slit diaphragms. Without a functional slit diaphragm, more molecules pass through the kidneys abnormally and get excreted in urine, including proteins and blood cells. The filtering ability of the kidneys worsens from birth, eventually leading to end-stage renal disease.

NPHS1 gene mutations cause all cases of congenital nephrotic syndrome of the Finnish type. This form of the condition is found in people of Finnish ancestry. NPHS1 gene mutations can cause congenital nephrotic syndrome in non-Finnish individuals, but they are a less common cause than NPHS2 gene mutations, which appear to be the most frequent cause of all cases.

Mutations in other genes cause a small number of cases of congenital nephrotic syndrome. Fifteen to 20 percent of individuals with congenital nephrotic syndrome do not have an identified mutation in one of the genes associated with this condition. In these cases, the cause of the condition may be environmental, including infections such as congenital syphilis or toxoplasmosis, or it may be caused by mutations in unidentified genes.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Congenital nephrotic syndrome affects 1 to 3 per 100,000 children worldwide. In Finland, where this condition is particularly common, congenital nephrotic syndrome is estimated to affect 1 in 10,000 children.

Which doctor should you see?

The suggested department for discussing Congenital nephrotic syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.