Tuberous sclerosis complex — clinical case

Case summary

This seven-month-old boy presents with the classic onset of tuberous sclerosis complex: clusters of flexor spasms (West syndrome) with developmental regression, hypomelanotic macules on Wood's lamp examination, a hypsarrhythmic EEG, and brain MRI showing cortical tubers and subependymal nodules. He already meets the 2012 consensus criteria for definite TSC through multiple major features, and the immediate priority is prompt control of his infantile spasms, because seizure control is the single most important determinant of developmental outcome. [3]

Key clinical issues

The first issue is the infantile spasms themselves. Flexor spasms in clusters with hypsarrhythmia and developmental regression constitute West syndrome, and in this setting TSC is the leading aetiology. Vigabatrin is first-line for TSC-associated infantile spasms and should be started promptly, because delay worsens the already high risk of intellectual disability and autism. The case also prompts a full baseline developmental and behavioural assessment, since neurocognitive comorbidity dominates long-term quality of life, and early intervention in the preschool years measurably improves function. [8]

The second issue is the broader surveillance that a TSC diagnosis demands. The same mTOR mechanism that produced his tubers and skin lesions also drives cardiac rhabdomyoma, renal angiomyolipoma and, later, subependymal giant cell astrocytoma and lymphangioleiomyomatosis. The maternal uncle's epilepsy and learning difficulty raise the possibility of familial disease, which makes a three-generation pedigree, parental examination and molecular testing essential for cascade counselling. [4]

Investigations and management

The diagnosis is already clinically secure from the 2012 criteria, and I would confirm with TSC1 and TSC2 sequencing and deletion analysis to enable cascade and reproductive testing. The baseline imaging set is complete with the brain MRI, and I would add an echocardiogram to look for a cardiac rhabdomyoma and an abdominal MRI or ultrasound to characterise renal angiomyolipomas and cysts. The immediate management is vigabatrin for the spasms with serial EEG, ophthalmic surveillance for visual-field toxicity, and referral to early intervention services. [1] [3]

The long-term plan is organ-by-organ surveillance coordinated through a multidisciplinary TSC clinic: brain MRI every one to three years through age 25 to detect a growing SEGA, annual developmental and behavioural review, renal imaging every one to three years, dermatology and ophthalmology input, and targeted lung surveillance when he reaches adulthood. If his seizures prove refractory or a SEGA grows, the mTOR inhibitor everolimus has evidence from the EXIST-3 and EXIST-1 trials respectively, acting downstream of the broken brake to restore control of mTORC1. Genetic counselling addresses the 50 per cent recurrence risk, and cascade testing of first-degree relatives is mandatory. [6] [4]

Discussion points

This case tests whether the candidate can integrate the diagnostic criteria, the molecular mechanism, and the surveillance programme, while acting on the time-critical issue of infantile spasms. The 2012 criteria confirm the diagnosis, the hamartin-tuberin-Rheb-mTORC1 mechanism explains why an mTOR inhibitor works for both SEGA and epilepsy, and the family history frames the discussion around autosomal-dominant inheritance and cascade testing. The candidate who frames seizure control as neuroprotection, and who closes with the family, demonstrates the fellowship standard. [1] [3]