A 14-year-old girl has multiple pinkish-brown papules over the nose and cheeks in a butterfly distribution, a large shagreen patch over the lumbosacral region, and periungual fibromas on two toes. MRI shows subependymal nodules. Mutation in which gene is the most common cause of this disorder?

• A TSC1 encoding hamartin
• B NF1 encoding neurofibromin
• C TSC2 encoding tuberin ✓
• D PTEN encoding phosphatase and tensin homologue

Explanation

Tuberous sclerosis complex results from mutations in TSC1 (hamartin) or TSC2 (tuberin), which negatively regulate mTOR signalling. TSC2 mutations account for roughly two thirds of cases and produce a more severe phenotype. The combination of facial angiofibromas, shagreen patch, periungual fibromas (Koenen tumours) and subependymal nodules is diagnostic. NF1 causes neurofibromas and Lisch nodules, while PTEN causes Cowden syndrome with trichilemmomas.

Reference: Rook's Textbook of Dermatology, 9th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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