Background

Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 and TSC2 genes, causing overactivation of the mechanistic (previously referred to as mammalian) target of rapamycin (mTOR) signaling pathway in fetal life. The mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy, intellectual disability, and autism spectrum disorder (ASD). Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic infants.

Data sources

We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms “tuberous sclerosis”, “autism”, or “autism spectrum disorder”,” animal models”, “preclinical studies”, “neurobiology”, and “treatment”.

Results

Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor, visual and social communication skills in the first year of life delays. Reliable genetic, cellular, electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and epilepsy.

Conclusions

Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC.

中文翻译：

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结节性硬化症相关自闭症是一种可以预防和治疗的疾病吗？

背景

结节性硬化症 (TSC) 是一种由TSC1和TSC2基因失活突变引起的遗传性疾病，导致胎儿生命中机械（以前称为哺乳动物）雷帕霉素靶点 (mTOR) 信号通路过度激活。 mTOR 通路在导致 TSC 相关癫痫、智力障碍和自闭症谱系障碍 (ASD) 的多种大脑过程中发挥着至关重要的作用。现在，越来越多的未出现症状的婴儿可以进行 TSC 的产前或产后早期诊断。

数据源

我们在 PubMed 上检索了 2010 年 1 月至 2023 年 4 月期间发表的同行评审出版物，其中包含术语“结节性硬化症”、“自闭症”或“自闭症谱系障碍”、“动物模型”、“临床前研究”、“神经生物学”和“治疗”。

结果

前瞻性研究强调，后来被诊断为自闭症谱系障碍 (ASD) 的 TSC 婴儿的发育轨迹在生命延迟的第一年就已经显示出运动、视觉和社交沟通技能。可靠的遗传、细胞、脑电图和磁共振成像生物标志物可以识别患有自闭症和癫痫高风险的症状前 TSC 婴儿。

结论

在敏感的发育时间窗口内预防癫痫或改善与针对自闭症的及时和量身定制的治疗策略相关的癫痫治疗可能有可能减轻 TSC 婴儿的自闭症症状。