关键词: 结节性硬化症, TSC1/TSC2基因, 癫痫, 新生变异, mTOR抑制剂

Abstract:

Objective This study aims to summarize the clinical features and TSC1/TSC2 gene variation analysis of 45 cases of tuberous sclerosis complex (TSC) diagnosed through genetic analysis, thereby enhancing the understanding of the disease. Methods Retrospectively collected and summarized clinical data of 45 children diagnosed with TSC associated with TSC1/TSC2 gene mutations and epilepsy from January 2018 to October 2021. Results Of the 45 children, 44 exhibited epilepsy, with 25 presenting with infantile spasms, 23 with generalized tonic-clonic seizures, 8 with myoclonic seizures, 6 with atonic seizures, 5 with dystonic seizures, and 20 with focal seizures. All patients showed skin depigmentation, with 6 presenting hemangiomas in the facial region. Cognitive impairment was observed in 25 cases, while 12 exhibited developmental delays. 6 had cardiac rhabdomyomas, 8 had renal cysts, 1 had polycystic kidneys, and 8 had retinal hamartomas. Genetic analysis revealed 15 patients with heterozygous mutations in the TSC1 gene (8 de novo and 7 inherited), including 4 frameshift mutations, 7 nonsense mutations, 2 missense mutations, and 2 splice mutations. In addition, 30 patients had heterozygous mutations in the TSC2 gene (21 de novo and 9 inherited), comprising 7 frameshift mutations, 4 nonsense mutations, 7 missense mutations, 3 whole-gene mutations, 7 splice sito mutations, 1 largo segmental deletion, and 1 extended mutotion. Notably, 1 TSC1 mutation and 10 TSC2 mutations were novel findings. Conclusion TSC presents with a diverse range of clinical symptoms, and the genotype-phenotype correlation is complex. Early genetic analysis of TSC1/TSC2 is essential for timely diagnosis and targeted treatment in suspected cases.

Key words: tuberous sclerosis, TSC1/TSC2 gene, epilepsy, de novo, mTOR inhibitors