TY - JOUR
T1 - Contemporary genetic testing in inherited cardiac disease
T2 - tools, ethical issues, and clinical applications
AU - Girolami, Francesca
AU - Frisso, Giulia
AU - Benelli, Matteo
AU - Crotti, Lia
AU - Iascone, Maria
AU - Mango, Ruggiero
AU - Mazzaccara, Cristina
AU - Pilichou, Kalliope
AU - Arbustini, Eloisa
AU - Tomberli, Benedetta
AU - Limongelli, Giuseppe
AU - Basso, Cristina
AU - Olivotto, Iacopo
PY - 2018/1
Y1 - 2018/1
N2 - : Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.
AB - : Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.
KW - Death, Sudden, Cardiac/etiology
KW - Europe
KW - Genetic Predisposition to Disease
KW - Genetic Testing/ethics
KW - Heart Diseases/diagnosis
KW - Humans
KW - Phenotype
KW - Practice Guidelines as Topic
KW - Societies, Medical
U2 - 10.2459/JCM.0000000000000589
DO - 10.2459/JCM.0000000000000589
M3 - Article
C2 - 29176389
VL - 19
SP - 1
EP - 11
JO - Journal of Cardiovascular Medicine
JF - Journal of Cardiovascular Medicine
SN - 1558-2027
IS - 1
ER -