Department of Pediatric Cardiology and Cardiac Surgery, Ospedale Pediatrico Bambino Gesù, IRCCS, 00165 Rome, Italy.
Department of Pediatrics, Obstetrics and Gynecology, "Sapienza" University, 00161 Rome, Italy.
Genes (Basel). 2021 Jul 8;12(7):1047. doi: 10.3390/genes12071047.
Recent advances in understanding the genetic causes and anatomic subtypes of cardiac defects have revealed new links between genetic etiology, pathogenetic mechanisms and cardiac phenotypes. Although the same genetic background can result in different cardiac phenotypes, and similar phenotypes can be caused by different genetic causes, researchers' effort to identify specific genotype-phenotype correlations remains crucial. In this review, we report on recent advances in the cardiac pathogenesis of three genetic diseases: Down syndrome, del22q11.2 deletion syndrome and Ellis-Van Creveld syndrome. In these conditions, the frequent and specific association with congenital heart defects and the recent characterization of the underlying molecular events contributing to pathogenesis provide significant examples of genotype-phenotype correlations. Defining these correlations is expected to improve diagnosis and patient stratification, and it has relevant implications for patient management and potential therapeutic options.
近年来，人们对心脏缺陷的遗传原因和解剖亚型的认识不断深入，揭示了遗传病因、发病机制和心脏表型之间的新联系。尽管相同的遗传背景可能导致不同的心脏表型，相似的表型也可能由不同的遗传原因引起，但研究人员努力确定特定的基因型-表型相关性仍然至关重要。在这篇综述中，我们报告了三种遗传疾病（唐氏综合征、del22q11.2 缺失综合征和 Ellis-Van Creveld 综合征）的心脏发病机制的最新进展。在这些情况下，与先天性心脏缺陷的频繁和特异性关联以及对导致发病机制的潜在分子事件的最新特征化提供了基因型-表型相关性的显著例子。定义这些相关性有望改善诊断和患者分层，并对患者管理和潜在治疗选择具有重要意义。
