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Europace. 2014 Dec;16(12):1838-46. doi: 10.1093/europace/euu128. Epub 2014 Jun 17.

Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype.

Author information

1
Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
2
Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain.
3
A Coruña University Hospital, A Coruña Biomedical Research Institute, A Coruña, Spain.
4
Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain jgimeno@secardiologia.es.

Abstract

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.

KEYWORDS:

Arrhythmogenic cardiomyopathy; Desmoplakin; Dilated cardiomyopathy; Implantable cardioverter-defibrillator; Sudden death

PMID:
24938629
DOI:
10.1093/europace/euu128
[Indexed for MEDLINE]

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