In pediatric TSC, whole-exome sequencing identified mutations in 93% of patients and revealed novel variants.

ObjectiveThis study analyzed the clinical and genetic characteristics of 73 pediatric patients with tuberous sclerosis complex (TSC). Through an examination of genotype-phenotype correlations, the research aimed to identify patterns in mutation characteristics to facilitate the optimization of diagnostic, therapeutic, and prognostic strategies.MethodsThis retrospective study analyzed pediatric patients with TSC at Nanjing Medical University Children's Hospital between February 2018 and June 2025. Clinical data, including demographics and initial manifestations, were reviewed and peripheral blood samples were collected for whole-exome sequencing. Statistical analysis of categorical variables was performed using the chi-square test.ResultsAmong the 73 pediatric TSC patients, 62 (85%) were diagnosed with epilepsy, with seizures being the initial manifestation in 56 (90%) of these cases. The observed seizure types included epileptic spasms (n = 25), generalized tonic-clonic seizure (n = 13), focal impaired consciousness seizure (n = 10), focal preserved consciousness seizure (n = 6), focal to bilateral tonic-clonic seizure (n = 5), tonic (n = 1), and absence (n = 1). Other common clinical features were hypopigmented macules (n = 44), cortical tubers (n = 34), intellectual disability (n = 24), and subependymal nodules (n = 22). Genetic testing identified TSC1 or TSC2 mutations in 68 patients (93%), corresponding to 71 distinct mutation sites. Fourteen variants (2 in TSC1, 12 in TSC2) were novel. The spectrum of mutations included nonsense, frameshift, missense, and splice-site types, with both de novo and inherited origins identified.ConclusionThe clinical phenotype of TSC is highly heterogeneous, with complex genotype-phenotype associations. The identification of 14 novel variants expands the known mutational spectrum of TSC, and the detailed genotype–phenotype analysis provides valuable insights for early diagnosis, genetic counseling, and personalized therapeutic strategies in pediatric populations. Early TSC1/TSC2 genetic testing is therefore crucial for diagnostic confirmation and enables personalized management strategies in cases of suspected TSC.