A Prospective Study of Sudden Cardiac Death among Children and Young Adults (original) (raw)
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Genetics of sudden cardiac death in the young
Clinical genetics, 2014
Sudden cardiac death (SCD) has an enormous impact on those who are left behind, evoking strong feelings of anxiety and incomprehension because such a dramatic event was not anticipated. Moreover, over the last decade a prominent genetic contribution to the pathogenesis of SCD has been unveiled. As many inherited cardiac diseases show an autosomal dominant pattern of inheritance, the risk of carrying the same inherited predisposition is a real concern for the relatives. In this article, we discuss the major causes of primary electrical disorders, cardiomyopathies and thoracic aortic dissection and address issues in genotype-phenotype correlation, personalized management and cardiogenetic counselling.
Sudden cardiac death in children and young adults—epidemiology and prevention
Cor et Vasa, 2012
Sudden cardiac death is a rare but catastrophic event in children and young adults (o35 years) with the incidence ranging between 0.8 and 2.8/100,000 person-years. Considering the frequent genetic background of potentially lethal cardiovascular disease in these patients, all attempts should be made to determine the risk for remaining family members. A population-based approach consists of screening young individuals being at higher risk (e.g. athletes) for potentially lethal cardiovascular disorders. The following text will analyse the efficacy of both approaches using currently available data.
Post-mortem genetic analysis in juvenile cases of sudden cardiac death
Forensic Science International, 2014
Molecular autopsy should be implemented in forensic protocols Nearly 40% of sudden death young cases carry a cardiac potentially pathogenic variant It is crucial to undertake a careful genetic analysis in a clinical context Genetic analyses help to identify relatives at risk of sudden death A c c e p t e d M a n u s c r i p t 2 Post-mortem genetic analysis in juvenile cases of sudden cardiac death Short Title: Genetic analysis in a forensic juvenile cohort Authors
Heart, Lung and Circulation, 2011
Nearly 30% of young sudden deaths have negative autopsies and these sudden unexplained deaths (SUDs) are presumed to be due to heritable cardiac arrhythmias attributed to cardiac ion channel disorders. Comprehensive cardiac and genetic testing of families of SUD is helpful in the detection of inherited cardiac genetic conditions. It frequently provides a clue to the cause of death in SUD victims and allows early diagnosis and opportunities to prevent SUD in other family members. Out of Hospital Cardiac Arrest (OHCA) victims and their families also require similar assessment, although the role of genetic testing in this group should be reserved to patients where a clinical diagnosis is established. A team approach with multidisciplinary specialised clinics and increased access to genetic analysis is very helpful in achieving these goals.
Contribution of Inherited Heart Disease to Sudden Cardiac Death in Childhood
PEDIATRICS, 2007
BACKGROUND. In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these investigations provide timely identification of relatives who are also at risk of sudden cardiac death. We aimed to establish the cause of sudden cardiac death in the children of whom the family was referred to our cardiogenetics department and the diagnostic yield of these investigations.
Rare Genetic Variants Associated With Sudden Cardiac Death in Adults
Journal of the American College of Cardiology
BACKGROUND Sudden cardiac death occurs in w220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection. OBJECTIVES This study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population. METHODS The authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death. RESULTS Among the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death-corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p < 0.0001). Among the 4,525 participants of the prospective cohort study, 41 (0.9%) carried a pathogenic or likely pathogenic variant and these individuals had 3.24-fold higher risk of cardiovascular death over a median follow-up of 14.3 years (p ¼ 0.02). CONCLUSIONS Gene sequencing identifies a pathogenic or likely pathogenic variant in a small but potentially important subset of adults experiencing sudden cardiac death; these variants are present in w1% of asymptomatic adults.
Sudden Cardiac Death—A New Insight Into Potentially Fatal Genetic Markers
Frontiers in Medicine, 2021
Sudden cardiac death (SCD) is an unexpected and dramatic event. It draws special attention especially in young, seemingly healthy athletes. Our scientific paper is based on the death of a young, 23-year-old professional footballer, who died on the football field after a two-year history of cardiac symptoms. In this study we analyzed clinical, ECG and laboratory data, as well as results of genetic testing analysis in family members. To elucidate potential genetic etiology of SCD in this family, our analysis included 294 genes related to various cardiac conditions.
The spectrum of epidemiology underlying sudden cardiac death
Circulation research, 2015
Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15%-20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who experience a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly because of inherited disorders. Coronary heart disease is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. During the past 3 decades, declines in SCD rates have not been as steep as for other causes of coronary heart disease deaths, and there is a growing fraction of SCDs not due to coronary heart disease and ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms u...
Genetics of Sudden Cardiac Death
Current Cardiology Reports, 2015
Sudden cardiac death (SCD) is defined by the World Health Organization (WHO) as death within 1 h of symptom onset (witnessed) or within 24 h of being observed alive and symptom free (unwitnessed). It affects more than 3 million people annually worldwide and affects approximately 1/1000 people each year in the USA. Familial studies of syndromes with Mendelian inheritance, candidate genes analyses, and genome-wide association studies (GWAS) have helped our understanding of the genetics of SCD. We will review the genetics of arrhythmogenic hereditary syndromes with Mendelian inheritance from familial studies with structural heart disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) as well as primary electrical causes (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome). In addition, we will review the genetics of intermediate phenotypes for SCD such as coronary artery disease and electrocardiographic variables (QT interval, QRS duration, and RR interval). Finally, we will review rare and common variants that are associated with SCD in the general population and were identified from candidate gene analyses and GWAS. Our understanding of the genetics of SCD will improve by the use of next-generation sequencing/ whole-exome sequencing as well as whole-genome sequencing which have the potential to discover unsuspected common and rare genetic variants that might be associated with SCD.