Tuberous sclerosis complex — diagnostic workup and management of an 8-month-old with ash-leaf macules and infantile spasms. — SAQ

Stem

An 8-month-old boy is brought by his parents for evaluation of "birthmark-like white spots" on his trunk since birth and new-onset clusters of flexion-extension spasms over the last six weeks. Examination reveals three oval, lance-shaped, hypomelanotic macules on the trunk (1–3 cm, better seen under Wood's lamp), a 1×2 cm yellowish, leathery plaque on the lower back, and bilateral, smooth, pink, dome-shaped papules over the nasolabial folds. EEG shows hypsarrhythmia. MRI brain shows multiple cortical tubers and two subependymal nodules at the foramen of Monro. The older sister has epilepsy and was told she had "small spots on her brain".

a) What is the most likely diagnosis and what features of this case confirm it? (2 marks)

b) What molecular mechanism underlies this disorder, and which genes are mutated? (2 marks)

c) Outline the immediate management plan, including first-line therapy for the infantile spasms and the staged organ-of-system evaluation. (3 marks)

d) What is the role of mTOR inhibitors (everolimus and topical sirolimus), and what adverse effects should be monitored? (2 marks)

e) What genetic counselling and surveillance would you offer the parents and the at-risk older sister? (1 mark)