Pang Nan, Chen Chen, Yang Lifen, Zhang Ciliu, Deng Xiaolu, Yang Li, Mao Leilei, Liu Fangyun, Wang Guoli, Duan Haolin, Wang Xiaole, Yin Fei, He Fang, Peng Jing
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, China.
BMC Med. 2025 Jul 1;23(1):388. doi: 10.1186/s12916-025-04220-w.
Epilepsy (EP) and intellectual disability (ID) are two highly correlated diseases that seriously impact neurodevelopment in children. Precision diagnosis of EP and ID remains challenging due to their clinical and genetic heterogeneity, necessitating a profound understanding of disease characteristics.
We provide a clinical and genetic landscape of 2261 Chinese patients performed chromosome microarray analysis (CMA) or next-generation sequencing to uncover causal copy number variants (CNVs) or single-nucleotide variants (SNVs). Patients were stratified into three groups: EP (374 cases), ID (863 cases), and EP + ID (1024 cases).
We reported a 24.3% diagnostic yield from 496 causal CNVs and SNVs, including 182 novel variants, in which updated 33 previously reported VUS. Significant intergroup differences emerged: EP patients were predominantly caused by autosomal dominant SNVs, showing the highest rates of incomplete penetrance and family history. ID patients were more likely caused by CNVs and autosomal recessive SNVs, with the highest genetic heterogeneity. EP + ID patients displayed the earliest onset ages and highest diagnostic yields. We prioritized genes by diagnostic efficiency and revealed that X-linked SNVs disproportionately affected females, particularly in the EP + ID group, under current diagnostic paradigms. This real-world dataset informs genetic counseling, testing strategies, precision therapies, and long-term management for EP/ID.
The clinical and genetic profiles from this study provided a reliable baseline reference for diagnosing EP and ID.
癫痫（EP）和智力残疾（ID）是两种高度相关的疾病，严重影响儿童的神经发育。由于其临床和遗传异质性，EP和ID的精准诊断仍然具有挑战性，因此有必要深入了解疾病特征。
我们提供了2261例中国患者的临床和遗传概况，这些患者进行了染色体微阵列分析（CMA）或下一代测序，以发现因果拷贝数变异（CNV）或单核苷酸变异（SNV）。患者被分为三组：EP（374例）、ID（863例）和EP+ID（1024例）。
我们报告了496个因果CNV和SNV的诊断率为24.3%，包括182个新变异，其中更新了33个先前报告的意义未明变异（VUS）。出现了显著的组间差异：EP患者主要由常染色体显性SNV引起，显示出不完全外显率和家族史的最高发生率。ID患者更可能由CNV和常染色体隐性SNV引起，具有最高的遗传异质性。EP+ID患者表现出最早的发病年龄和最高的诊断率。我们根据诊断效率对基因进行了优先排序，并发现X连锁SNV对女性的影响不成比例，特别是在当前诊断模式下的EP+ID组中。这个真实世界的数据集为EP/ID的遗传咨询、检测策略、精准治疗和长期管理提供了信息。
本研究的临床和遗传特征为诊断EP和ID提供了可靠的基线参考。
