先天性心脏病伴神经发育障碍的临床表现及遗传学研究进展

Clinical manifestations and genetics research progress of congenital heart disease with neurodevelopmental disorders in children

近年来研究发现先天性心脏病(CHD)患儿伴神经发育障碍(NDDs)的风险正逐年增加,包括认知、适应性、运动、语言、孤独症谱系障碍等。已通过结构及功能神经成像等影像学检查证实CHD患儿大脑发育存在异常,可能为宫内发育不良所致。拷贝数变异(CNVs)等基因异常对CHD伴NDDs具有重要影响。一些参与载脂蛋白E产生、Wnt信号传导通路和组蛋白修饰的基因变异以及1q21.1、16p13.1-11和8p23.1遗传位点变异均与CHD和NDDs相关。了解其中的相互联系对CHD患者的风险分层、疾病分类、筛查及药物治疗具有重要意义。

Recent studies have found that children with congenital heart disease(CHD)are at increased risk of neurodevelopmental disorders(NDDs),including cognitive,adaptive,motor,speech and autism spectrum disorders.Structural and functional neuroimaging has indicated that brain abnormalities in children with CHD might be caused by an in utero developmental insult.Specific genetic abnormalities,particularly copy number variants(CNVs),have been increasingly implicated in both CHD and NDDs.Variations in genes involved in apolipoprotein E production,the Wnt signaling pathway,and histone modification,as well as in the 1q21.1,16p13.1-11 and 8p23.1 genetic loci,are associated with CHD and NDDs.Understanding these associations is important for risk stratification,disease classification,improving screening and pharmacologic management of individuals with CHD.