Key High-Risk Genes in Dilated Cardiomyopathy: Desmoplakin (DSP)

초록

Background Desmoplakin (DSP) is a critical component of the desmosome, essential for maintaining structural integrity between cardiac myocytes and epidermal cells. While pathogenic variants in the DSP gene are known to cause Dilated Cardiomyopathy (DCM) and Arrhythmogenic Cardiomyopathy (ACM), their clinical presentation often diverges from the classic Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Clinical Characteristics DSP cardiomyopathy is characterized by a high prevalence of left-ventricular (LV) dominant or bi-ventricular involvement, rather than the isolated right-ventricular involvement seen in typical ARVC. A distinctive feature is the occurrence of "hot phases"?episodes of acute myocardial injury presenting with chest pain and elevated troponins?which can lead to misdiagnosis as myocarditis or sarcoidosis. Furthermore, significant LV fibrosis (detected via Late Gadolinium Enhancement, LGE) often precedes the decline in systolic function (LVEF). Risk Stratification and Prognosis Patients with DSP variants face a high risk of sustained ventricular arrhythmias (SVA) and heart failure. Key risk factors for SVA include an LVEF below 55%, frequent premature ventricular contractions (PVCs > 500/24h), and a history of acute myocardial injury. Notably, current Task Force Criteria (TFC) for ARVC may fail to identify at-risk DSP patients; studies show that a significant portion of patients experiencing SVA do not meet the traditional TFC diagnostic thresholds. Conclusion DSP cardiomyopathy should be recognized as a unique disease entity with a distinct phenotype and high arrhythmic risk. Effective management requires genotype-specific risk stratification and early clinical intervention, particularly for patients presenting with myocardial injury or extensive fibrosis, to improve long-term clinical outcomes.