Delayed diagnosis of tuberous sclerosis complex in a young adult with long-term refractory epilepsy: a case report

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous hamartomatous disorder characterized by widespread multi-system hamartomatous lesions, with epilepsy occurring in the majority of affected patients. When refractory epilepsy serves as the sole long-standing clinical manifestation, subtle cutaneous and radiological hallmarks are easily overlooked, inevitably leading to diagnostic delay. We herein report a 23-year-old female patient presenting with a decade-long history of drug-refractory seizures. Physical examination revealed mild cognitive impairment with a Mini-Mental State Examination (MMSE) score of 22 (technical secondary school education) and no focal neurological deficits. A typical lumbosacral shagreen patch and a surgical scar from prior great toe periungual fibroma resection were identified on cutaneous inspection. Brain MRI demonstrated white matter migration lines on fluid-attenuated inversion recovery (FLAIR) sequences, while cranial CT detected subependymal calcified nodules. Sanger genetic sequencing confirmed a heterozygous pathogenic splice-site variant NM_000368.5:c.107-2A > G in the TSC1 . Given her childbearing potential, valproate was gradually tapered and substituted with lamotrigine to minimize teratogenic risks. Sirolimus-mediated mTOR-targeted therapy was initiated alongside renoprotective agents and regular serial imaging surveillance. Optimized combination therapy yielded a remarkable reduction in seizure frequency during follow-up. TSC may manifest insidiously for years with refractory epilepsy as its only prominent clinical feature. Comprehensive screening consisting of thorough cutaneous examination, standardized cranial imaging and molecular genetic testing is mandatory for early identification of this disorder. Individualized antiseizure regimens combined with mechanistic target of rapamycin (mTOR) inhibitors can significantly improve seizure control and long-term clinical outcomes in TSC patients.