Abstract
Background:Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC.Methods:We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected.Results:Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%).Conclusions:Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.
Highlights
Academic Editors: Tiina Heliö, Abstract: Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly
Forty percent of familial dilated cardiomyopathy (DCM) has an identifiable genetic cause and over 60 genes associated with familial DCM have been reported [1]
Natural history studies have demonstrated that pathogenic variants in DCM-associated genes, such as lamin A/C (LMNA), filamin C (FLNC), cardiac sodium channel NAv1.5 published maps and institutional affiliations
Summary
Academic Editors: Tiina Heliö, Abstract: Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly. Genetic variation in DSP has been associated with left-dominant arrhythmogenic cardiomyopathy. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. The expanding use of clinical genetic testing in patients with heart failure is facilitating new insights into the causes of dilated cardiomyopathy (DCM). Natural history studies have demonstrated that pathogenic variants in DCM-associated genes, such as lamin A/C (LMNA), filamin C (FLNC), cardiac sodium channel NAv1.5 published maps and institutional affiliations. Natural history studies have demonstrated that pathogenic variants in DCM-associated genes, such as lamin A/C (LMNA), filamin C (FLNC), cardiac sodium channel NAv1.5
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