A 2-year-old boy has ash-leaf macules, a shagreen patch, and infantile spasms that started at 4 months of age. MRI of the brain shows cortical tubers and subependymal nodules. This syndrome is associated with mutations in which genes?

• A NF1 and NF2
• B VHL and APC
• C TSC1 (hamartin) and TSC2 (tuberin) ✓
• D PTEN and BRCA1

Explanation

Tuberous sclerosis complex (TSC) is caused by autosomal dominant mutations in TSC1 (encoding hamartin, chromosome 9q34) or TSC2 (encoding tuberin, chromosome 16p13). Loss of hamartin/tuberin leads to overactivation of mTOR pathway causing hamartomatous growths. Classic triad: cortical tubers (seizures), subependymal nodules (risk of giant cell astrocytoma), and skin lesions (ash-leaf macules, shagreen patch, facial angiofibromas). Infantile spasms are the most common early seizure type.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.