A newborn boy presents with massive proteinuria, edema, and a markedly enlarged placenta. His parents are first cousins. Renal biopsy shows dilated proximal tubules forming microcysts, and electron microscopy reveals complete effacement of foot processes with absent slit diaphragms. Steroids fail to induce remission. The defective gene encodes:

• A Podocin (NPHS2)
• B Nephrin (NPHS1) ✓
• C Alpha-actinin 4 (ACTN4)
• D Collagen IV alpha5 chain (COL4A5)

Explanation

Congenital nephrotic syndrome of the Finnish type is an autosomal recessive disease caused by NPHS1 mutations encoding nephrin, the key slit diaphragm protein. It presents at birth with placentomegaly and is steroid resistant because the structural protein is absent. Podocin mutations usually cause steroid-resistant nephrotic syndrome in childhood rather than at birth, ACTN4 causes autosomal dominant adult FSGS, and COL4B5 causes Alport syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.