Congenital heart diseases (CHDs) are the most common congenital anomalies with an estimated prevalence of 8 in 1000 live births. CHDs occur as a result of abnormal embryogenesis of the heart. Congenital heart diseases are associated with significant mortality and morbidity. The damage of the heart is irreversible due to a lack of regeneration potential, and usually, the patients may require surgical intervention. Studying the developmental biology of the heart is essential not only in understanding the mechanisms and pathogenesis of congenital heart diseases but also in providing us with insight towards developing new preventive and treatment methods. The etiology of congenital heart diseases is still elusive. Both genetic and environmental factors have been implicated to play a role in the pathogenesis of the diseases. Recently, cardiac transcription factors, cardiac-specific genes, and signaling pathways, which are responsible for early cardiac morphogenesis have been extensively studied in both human and animal experiments but leave much to be desired. The discovery of novel genetic methods such as next generation sequencing and chromosomal microarrays have led to further study the genes, non-coding RNAs and subtle chromosomal changes, elucidating their implications to the etiology of congenital heart diseases. Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, and abnormal hemodynamics in causing CHDs. These etiological factors raise questions on multifactorial etiology of CHDs. It is therefore important to endeavor in research based on finding the causes of CHDs. Finding causative factors will enable us to plan intervention strategies and mitigate the consequences associated with CHDs. This review, therefore, puts forward the genetic and non-genetic causes of congenital heart diseases. Besides, it discusses crucial signaling pathways which are involved in early cardiac morphogenesis. Consequently, we aim to consolidate our knowledge on multifactorial causes of CHDs so as to pave a way for further research regarding CHDs. The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.

中文翻译：

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先天性心脏病：遗传学、非遗传性危险因素和信号通路

先天性心脏病 (CHD) 是最常见的先天性异常，估计每 1000 名活产婴儿中就有 8 人患病。CHD 是由于心脏胚胎发生异常引起的。先天性心脏病与显着的死亡率和发病率有关。由于缺乏再生潜力，心脏的损伤是不可逆的，通常，患者可能需要手术干预。研究心脏的发育生物学不仅对了解先天性心脏病的机制和发病机制至关重要，而且还为我们提供开发新的预防和治疗方法的见解。先天性心脏病的病因仍然难以捉摸。遗传和环境因素都与疾病的发病机制有关。最近，心脏转录因子、心脏特异性基因和信号通路负责早期心脏形态发生，已在人类和动物实验中得到广泛研究，但仍有许多不足之处。新一代测序和染色体微阵列等新型遗传方法的发现导致了对基因、非编码 RNA 和细微染色体变化的进一步研究，阐明了它们对先天性心脏病病因学的影响。研究还表明风疹感染、致畸剂、母亲年龄、糖尿病和异常血流动力学等非遗传性危险因素会导致冠心病。这些病因对冠心病的多因素病因提出了质疑。因此，在寻找 CHD 病因的基础上进行研究是很重要的。寻找致病因素将使我们能够规划干预策略并减轻与 CHD 相关的后果。因此，本综述提出了先天性心脏病的遗传和非遗传原因。此外，它还讨论了参与早期心脏形态发生的关键信号通路。因此，我们的目标是巩固我们对 CHD 多因素原因的认识，为进一步研究 CHD 铺平道路。先天性心脏病的多因素病因给我们提出了明确确定具体致病因素并因此计划干预策略的挑战。更精心设计的研究和新型遗传技术的使用可能是发现与先天性心脏病发病机制有关的病因因素的途径。