Cardiogenetics, 25 years a growing subspecialism

Abstract

The cardiology and clinical genetics subspecialty of cardiogenetics has experienced a tremendous growth in the past 25 years. This review discusses examples of the progress that has been made as well as new challenges that have arisen within this field, with special focus on the Netherlands. A significant number of Dutch founder mutations, i.e. mutations shared by a number of individuals who have a common origin and all share a unique chromosomal background on which the mutation occurred, have been identified and have provided unique insights into genotypephenotype correlations in inherited arrhythmia syndromes and inherited cardiomyopathies. Cardiological and genetic screening of family members of young victims of sudden cardiac death combined with genetic testing in the deceased individual have turned out to be rewarding. However, the interpretation of the results of genetic testing in this setting and in the setting of living patients with a (suspected) phenotype is now considered more challenging than previously anticipated, because the introduction of high-throughput sequencing technologies has resulted in the identification of a significant number of variants of unknown significance. Interpretation of genetic and clinical findings by experienced multidisciplinary teams are key to ensure a high quality of care to the patient and the family.

Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status

“…Thus, cardiogenetics, a rapidly growing subspecialty that combines the fields of cardiology and clinical genetics, aims at the investigation of the genetic factors underlying cardiovascular diseases. By focusing on identifying and understanding these genetic factors, cardiogenetics serves to improve the diagnosis, treatment, and prevention strategies for different heart conditions [ 209 ].…”

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities

“…Genetic testing (GT) results aid in individualized and more informative counseling in families especially through identification of carriers of asymptomatic pathogenic or likely pathogenic (P/LP) variants, which in many cases enables prevention of sudden cardiac death (SCD). Cardiology guidelines incorporate GT results in recommendations for diagnosis and personalized clinical management [12,13] although the usefulness of establishing a genetic cause varies between disease entities (Table 1) [14].…”

“…al. [14] Abbreviations: AVRC, arrhythmogenic right ventricular cardiomyopathy; BrS, Brugada syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; DCM, dilated cardiomyopathy; FH, familial hypercholesterolemia; fTAAD, familial thoracic aortic aneurysm and dissection; HCM, hypertrophic cardiomyopathy; LQTS, long QT syndrome; NDLVC, non-dilated left ventricular cardiomyopathy; RCM, restrictive cardiomyopathy; SQTS, short QT syndrome continuous increase in knowledge, the yield of GT varies between 20%-75 % depending on the disease. Negative GT results in the proband does not exclude any assumed diagnosis and, in this case, does not exempt the proband's family members from routine evaluations.…”

Optical Mapping in hiPSC-CM and Zebrafish to Resolve Cardiac Arrhythmias

“…Due to this, elucidating the pathophysiological mechanisms behind the ICAs and identifying patients remains challenging. Over the past two decades, molecular genetic screening of affected individuals and their families has become a standard genetic practice and significantly aids in overcoming the aforementioned hurdles [4]. However, in BrS for instance, only in around 20-25% of the cases can a genetic diagnosis be obtained, leaving a large grey area of BrS patients without a clear pathogenetic mechanism [5].…”