A 2-year-old phenotypic male child has ambiguous genitalia, nephrotic-range proteinuria, and progressive renal failure. Ultrasound shows a renal mass and biopsy reveals mesangial sclerosis. Which gene is mutated and what associated malignancy must be screened for?

• A WT1 mutation, screen for Wilms tumor ✓
• B NPHS1 mutation, screen for neuroblastoma
• C COL4A5 mutation, screen for hepatoblastoma
• D PKHD1 mutation, screen for rhabdomyosarcoma

Explanation

Denys-Drash syndrome comprises WT1 gene mutation, diffuse mesangial sclerosis causing early onset nephrotic syndrome, male pseudohermaphroditism from defective gonadal development, and a very high risk of Wilms tumor. Affected children need serial abdominal imaging for Wilms tumor. COL4B5 causes Alport syndrome with hereditary nephritis and deafness, while PKHD1 causes autosomal recessive polycystic kidney disease.

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.