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Congenital nephrotic syndrome, Finnish type
Congenital nephrotic syndrome, Finnish type is characterised by protein loss beginning during foetal life.
This type of nephrotic syndrome is more frequent in Finland (with an incidence of 1 in 8 200 births) but it is also observed in various ethnic groups worldwide.
Symptoms observed at birth are linked to protein deficiency. Children affected by the disease are born prematurely in more than 80% of cases, and have low birth weight (approximately 2600g). Placental volume is increased and constitutes more than 25% of the birth weight. Histologically, microcytic dilatations of the tubules are seen, whereas glomeruli are only slightly modified initially.
It is caused, in Finnish families as well as in other families, by mutations in the NPHS1 gene, localised to chromosome 19. Several mutations have been identified, among which two are predominant in the Finnish population: one is a two base pair deletion in exon 2 (Fin major) and the other a nonsense mutation in exon 26 (Fin minor). These two mutations are observed in 90% of Finnish patients, in either a homozygous or compound heterozygous state. About 50 mutations have been identified outside Finland.
Antenatal diagnosis can be performed. The nephrotic syndrome begins early, as soon as the 15th week of gestation, leading to a 10-fold increase in alpha-foetoprotein concentration in the amniotic fluid and a parallel but smaller rise in the maternal serum level. These anomalies can allow antenatal diagnosis in families with increased risk of the disease. However, heterozygous mutations in the NPHS1 gene can also lead to increased levels of alpha-foetoprotein, leading to misdiagnosis. The identification of the gene now allows antenatal diagnosis to be performed either through linkage studies with microsatellites in informative families or through gene analysis on a trophoblastic sample when the mutation of the causative gene has been identified in an affected child from the family.
The disease is transmitted as an autosomal recessive trait.
Management and treatment
The nephrotic syndrome is severe; it is resistant to corticosteroids and immunosuppressant drugs and progresses to end-stage renal disease. Infectious and nutritional complications are common, due to the massive protein loss. Initiation of dialysis/transplantation can be proposed. The disease does not recur in the graft.