By definition: a nephrotic syndrome that presents during the first 3 months of life: protein leakage, hypoalbuminemia, edemas.

The term 'Infantile nephrotic syndrome' is used when the disease presents in the first year of age but after 3 months of age.

Variable genetic origin: it is most often an autosomal recessive podocytopathy:

• mutation of the NPSH1 (19q13.12) or NPSH2 (1q25.2) gene: responsible for Finnish-type congenital nephrotic syndrome (see this term)
• mutation of the PLCE1 gene (10q23.33) coding for phospholipase: 1-phosphatidylinositol-4.5-bisphosphate phosphodiesterase epsilon-1 (PLCE1)
• mutation of the WT1 gene (11p), the Wilms Tumor suppressor gene, (Denys-Drash syndrome) associated with a high risk of nephroblastoma (see this term)
• mutation of the LAMB2 gene (3p21), coding for laminin beta 2 which is part of the glomerular basal membrane, responsible for Pierson syndrome (congenital microcoria-nephrosis) (see this term)
• TRPC6 (11q22.1): calcium channel abnormalities resulting in autosomal dominant  familial glomerulosclerosis

• ACTN4 (19q13.2): abnormality of the podocytes that results in segmental focal glomerulosclerosis

In 15 % of cases, the congenital nephrotic syndrome is secondary to :

-        a congenital infection: syphilis, toxoplasmosis, CMV, rubella, hepatitis B, HIV

-        maternal alloimmune disease

-        a mitochondrial cytopathy: mutation of the PDSS2 (6q21) or COQ2 (4q21.23) nuclear gene, resulting in mutation of the ubiquinone of the mitochondrial respiratory chain

-        fetomaternal alloimmunization against a podocyte protein responsible for congenital membranous nephropathy.

Significant morbidity and mortality.

Treatment:

-        IV albumin: to maintain blood volume

-        treatment with converting enzyme inhibitor or indomethacin to reduce proteinuria,

-        uni- or bilateral nephrectomy (around 7-8 kg),

-        peritoneal dialysis in case of renal failure,

-        early renal transplantation (as soon as the child weighs 10 kg).

-        thromboprophylaxis because of secondary hypercoagulability (low serum ATIII levels)

-        often secondary hypothyroidism (protein leakage)

Anesthetic implications:

check blood electrolytes, creatininemia, total blood count and thyroid function; difficult venous access; risk of thrombosis (central venous access); antibioprophylaxis.

Treatment with conversion enzyme inhibitor. Management of the volemia. Peritoneal dialysis or hemodialysis. Risk of persistent arterial hypotension and neurological complications after bilateral nephrectomy. Beware of the risk of hypertriglyceridemia in the case of TIVA with propofol.

References :

-            van Lieburg AF, Monnens LAH.
Persistent arterial hypotension after bilateral nephrectomy in a 4-month-old infant.
Pediatr Nephrol 2001 ; 16 :604-5

-        Dufek S, Hollta T, Trautmann A, Ylinen E, Alpay H et al.
Management of children with congenital nephrotic syndrome : challenging treatment paradigms.
Nephrol Dial Transplant 2019 ; 34 :1369-77 

-        Fares F, Laval N, Assy J, Mulder A.
Syndrome néphrotique congénital de type finlandais en période néonatale : défis diagnostiques et thérapeutiques.
Louvain Médical 2024 ; 143 : 533-9.

Updated: December 2024