A 3-year-old is brought with hypopigmented macules on the trunk, ash-leaf spots, shagreen patches on the back, and multiple periungual fibromas. He has seizures since 6 months of age and is hyperactive with attention problems. Brain MRI reveals cortical tubers. This condition is associated with mutations in which genes?
- A NF1 and NF2
- B VHL and PTEN
- C APC and RB1
- D TSC1 (hamartin) and TSC2 (tuberin) ✓
Explanation
Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 (encoding hamartin, chromosome 9q34) or TSC2 (encoding tuberin, chromosome 16p13.3). Both proteins form a complex that inhibits mTORC1; mutations lead to uncontrolled mTOR activation causing hamartomas in multiple organs. Classic dermatological features include hypomelanotic macules (ash-leaf spots), shagreen patches (connective tissue nevi), angiofibromas (adenoma sebaceum), and periungual fibromas. Cortical tubers cause epilepsy and intellectual disability. Everolimus (mTOR inhibitor) is now used therapeutically for subependymal giant cell astrocytoma (SEGA) in TSC.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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