A 30-year-old woman has facial angiofibromas, multiple hypomelanotic macules (ash-leaf spots) on the trunk, and a history of infantile spasms. Fundoscopy reveals retinal astrocytic hamartomas. Which gene is most likely mutated?
- A NF1 on chromosome 17
- B TSC1 on chromosome 9 or TSC2 on chromosome 16 ✓
- C NF2 on chromosome 22
- D VHL on chromosome 3
Correct answer: B. TSC1 on chromosome 9 or TSC2 on chromosome 16
Explanation
Tuberous sclerosis complex (TSC) is characterized by the triad of facial angiofibromas, seizures (including infantile spasms), and intellectual disability. Hypomelanotic macules, retinal hamartomas, and cortical tubers are hallmark features. TSC results from mutations in TSC1 (hamartin) or TSC2 (tuberin), which normally inhibit the mTOR pathway. NF1 causes café-au-lait spots and neurofibromas. NF2 causes bilateral vestibular schwannomas. VHL causes renal cell carcinoma and hemangioblastomas.
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.