NPHS1 gene

Also known as: Nephrotic syndrome, type 1; Congenital nephrotic syndrome


1. The Disease:

A rare congenital nephrotic syndrome characterized by massive protein loss and marked edema manifesting in utero or during the first 3 months of life. This type of nephrotic syndrome is more frequent in Finland with a prevalence of 1/8,200 births. The disease is observed in various ethnic groups worldwide but the prevalence is unknown.

2. The Symptoms:

Severe nephrotic syndrome develops soon after birth; typical features include hypoalbuminemia, hyperlipidaemia, hypothyreosis, abdominal distension and oedema with associated failure to thrive, increased susceptibility to thromboembolic events and severe infections. Lack of early signs or symptoms does not exclude the diagnosis.

  • Affected children show massive proteinuria and oedema starting in utero (foetal hydrops). Children usually have low birth weight and are born prematurely; the weight of the placenta constitutes more than 25% of the birth weight.
  • Histologically, microcystic dilatations of the tubules are seen whereas glomeruli are only slightly modified initially, with variable mesangial cell hypercellularity and/or endocapillary hypercellularity. Electron microscopy shows glomerular effacement of the podocytes.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test (2 different mutations or 1 mutation in homozygous state in the NPHS1 gene) should continue breastfeeding
  • The diagnosis is based on genetic results, familial history, clinical signs, and eventually renal biopsy.
  • CNS, Finnish type is a lifelong condition that requires lifetime management and regular follow-up with a nephrology specialist and a multidisciplinary approach to care, including paediatrics and genetics.
  • The nephrotic syndrome does not respond to any immunosuppressive therapy and treatment is largely symptomatic, comprising frequent albumin infusions, anti-proteinuric pharmacotherapy with RAS (renin-angiotensin system) inhibitors and indomethacin, anticoagulation, thyroid hormone supplementation and aggressive treatment of infections.
  • With adequate supportive care, most children survive long-term but develop end-stage kidney disease requiring renal replacement therapy within the first 2-3 years of life. Five-year patient and graft survival after transplantation is around 90%, similar as in infants with other causes of end-stage kidney disease. Post-transplant disease recurrence is limited to patients who are homozygous for the Finnish major mutation (a rare 2 base pair deletion in exon 2 of NPHS1), who have a 30% risk to develop de novo glomerulonephritis due to circulating anti-nephrin antibodies.
  • The pattern of disease transmission is autosomal recessive. The risk of recurrence in siblings of an affected individual is 25%. Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings, especially in X-linked cases.

4. For more information: