A child evaluated for congenital nephrotic syndrome is noted to have dystrophic fingernails, absence of the patellae, and iliac horns on pelvic radiograph. Renal biopsy electron microscopy shows irregular thickening of the glomerular basement membrane with bundles of banded collagen fibrils within it. The mutated gene responsible encodes:

• A COL4A5, the alpha5 chain of type IV collagen
• B LMX1B, a transcription factor involved in glomerular development ✓
• C NPHS2, encoding podocin
• D WT1, a transcription factor of the podocyte nucleus

Explanation

This is nail-patella syndrome (hereditary osteoonychodysplasia), caused by mutation in LMX1A, a transcription factor regulating podocyte and limb development. Its renal hallmark on electron microscopy is irregular GBM thickening with lucent areas containing cross-banded collagen fibrils, giving a moth-eaten appearance. COL4B5 mutation gives Alport syndrome without skeletal changes, and WT1 mutation produces Denys-Drash syndrome with mesangial sclerosis and gonadoblastoma risk.

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.