Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, 94103, USA.
Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, Falk CVRB room CV-154, 870 Quarry Road, Stanford, CA, 94305, USA.
Curr Cardiol Rep. 2022 Sep;24(9):1077-1084. doi: 10.1007/s11886-022-01727-z. Epub 2022 Jul 28.
The disease burden of inherited dilated cardiomyopathy (DCM) is large and likely underestimated. This population stands to benefit immensely from therapeutic approaches tailored to the underlying genetic causes. Here, we review recent advances in understanding novel genotype-phenotype relationships and how these can improve the care of patients with inherited DCM.
In the last several years, discovery of novel DCM-associated genes, gene-specific DCM outcomes, and nuanced information about variant-environment interactions have advanced our understanding of inherited DCM. Specifically, novel associations of genes with specific clinical phenotypes can help to assess sudden cardiac death risk and guide counseling around behavioral and environmental exposures that may worsen disease. Important expansions of the current genotype-phenotype profiling include the newly DCM-associated FLNC variant, prognostically significant LMNA, DSP inflammatory cardiomyopathy, and the highly penetrant features of RBM20 variants as well as the role of TTN variants in compounding the effects of environmental factors on toxin-mediated DCM. Future directions to improve diagnostic accuracy and prognostic improvement in DCM will center not just on identification of new genes, but also on understanding the interaction of known and novel variants in known DCM genes with patient genetic background and environment.
遗传性扩张型心肌病（DCM）的疾病负担很大，而且可能被低估了。这一人群将从针对潜在遗传原因的治疗方法中受益匪浅。在这里，我们回顾了近年来对新的基因型-表型关系的理解，以及这些如何改善遗传性 DCM 患者的护理。
在过去的几年中，发现了新的 DCM 相关基因、基因特异性 DCM 结果以及关于变异-环境相互作用的细微信息，这些都提高了我们对遗传性 DCM 的认识。具体来说，与特定临床表型相关的新基因关联有助于评估心脏性猝死风险，并指导关于可能使疾病恶化的行为和环境暴露的咨询。目前基因型-表型分析的重要扩展包括新的 DCM 相关 FLNC 变体、具有预后意义的 LMNA、DSP 炎症性心肌病以及 RBM20 变体的高度外显率特征，以及 TTN 变体在复合环境因素对毒素介导的 DCM 的影响中的作用。改善 DCM 诊断准确性和预后的未来方向不仅将集中在识别新基因上，还将集中在理解已知和新的 DCM 基因变体与患者遗传背景和环境的相互作用上。
