AIMS: Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations. METHODS AND RESULTS: Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging. CONCLUSION: DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations. METHODS AND RESULTS: Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging. CONCLUSION:DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Ronald Ng; Heather Manring; Nikolaos Papoutsidakis; Taylor Albertelli; Nicole Tsai; Claudia J See; Xia Li; Jinkyu Park; Tyler L Stevens; Prameela J Bobbili; Muhammad Riaz; Yongming Ren; Christopher E Stoddard; Paul Ml Janssen; T Jared Bunch; Stephen P Hall; Ying-Chun Lo; Daniel L Jacoby; Yibing Qyang; Nathan Wright; Maegen A Ackermann; Stuart G Campbell Journal: JCI Insight Date: 2019-06-13
Authors: Eric D Smith; Neal K Lakdawala; Nikolaos Papoutsidakis; Gregory Aubert; Andrea Mazzanti; Anthony C McCanta; Prachi P Agarwal; Patricia Arscott; Lisa M Dellefave-Castillo; Esther E Vorovich; Kavitha Nutakki; Lisa D Wilsbacher; Silvia G Priori; Daniel L Jacoby; Elizabeth M McNally; Adam S Helms Journal: Circulation Date: 2020-05-06 Impact factor: 29.690
Authors: Leila Rouhi; Siyang Fan; Sirisha M Cheedipudi; Aitana Braza-Boïls; Maria Sabater Molina; Yan Yao; Matthew J Robertson; Cristian Coarfa; Juan R Gimeno; Pilar Molina; Priyatansh Gurha; Esther Zorio; Ali J Marian Journal: Cardiovasc Res Date: 2022-05-06 Impact factor: 13.081