Genetic counselling implementation in dilated cardiomyopathy.
👥 作者
Job A J Verdonschot
(Department of Clinical Genetics/The Netherlands)
Karin Y van Spaendonck-Zwarts
(Department of Clinical Genetics/The Netherlands)
Debby M E I Hellebrekers
(Department of Clinical Genetics/The Netherlands)
Folkert W Asselbergs
(Department of Cardiology/The Netherlands)
Elijah R Behr
(Cardiovascular and Genomics Research Institute/UK)
Philippe Charron
(Filière Nationale de Santé CARDIOGEN/France)
Dana Dawson
(Aberdeen Cardiovascular and Diabetes Centre/UK)
Pablo Garcia-Pavia
(Heart Failure and Inherited Cardiac Diseases Unit/Spain)
Kristina H Haugaa
(Department of Cardiology/Sweden)
Ruxandra Jurcut
(Expert Center for Genetic Cardiovascular Diseases/Romania)
Petr Kuchynka
(2nd Department of Medicine/Czech Republic)
Luis R Lopes
(Barts Heart Centre/UK)
Andrea Mazzanti
(Molecular Cardiology Unit/Italy)
Marco Metra
(Cardiology/Italy)
Lorenzo Monserrat
(Medical Department/Spain)
Juan Pablo Kaski
Antonis Pantazis
Sanjay K Prasad
Giuseppe Rosano
Petar M Seferovic
Mary N Sheppard
Gianfranco Sinagra
Maria Teresa Tome Esteban
Stephane R B Heymans
J Peter van Tintelen
📝 摘要
Genetic testing has become an integral part of the diagnostic workup of patients with dilated cardiomyopathy (DCM). While the initial goal of genetic testing was to identify family members at risk, recent advances have now extended their relevance to clinical decision-making. Our knowledge of the genetic architecture of DCM has expanded significantly, promoting a shift from the monogenic dogma towards a broader polygenic spectrum. However, current genetic testing strategies still primarily rely on the model of monogenic inheritance with an incomplete penetrance. Large studies have shown a yield varying from 8% to 36% of genetic testing in patients with DCM, depending on aetiology or family history. Genetic testing is generally warranted for every patient with DCM where genetic results could have an impact on risk stratification, the prognosis or the treatment of the patient, or its family members with an opportunity for reassurance or early disease detection. There are various strategies for genetic testing including broad multigene panels, or more targeted panels limited to specific disease-associated genes. Identified variants are classified by genetic laboratories, where pathogenic or likely pathogenic variants often have actionable clinical implications. It is crucial to interpret these variants in the context of the individual patient considering the phenotype and other contributing factors. When the genetic results are consistent with the patients' broader phenotype, potential clinical implications may include decision for device therapy, recommendations for family screening, and reproductive options. A comprehensive approach to integrate genetic testing in the clinical care of patients with DCM is proposed.