Delayed diagnosis of tuberous sclerosis complex: unveiling low-level TSC2 mosaicism using targeted next-generation sequencing

Our case illustrates the clinical and diagnostic challenges presented by tuberous sclerosis complex (TSC), notably when the clinical signs are few and subtle, and the molecular pathology involves mosaicism and presence of a low percentage of the mutant variant in target tissues. The result aligns with previous findings that a significant number of individuals exhibit low-level mosaicism for a TSC1/TSC2 pathogenic variant without clinical recognition, and underscores the utility of next-generation sequencing technologies in the genetic study of TSC. Moreover, a deeper understanding of the molecular pathology of TSC-associated tumours improves genetic counselling and disease management.