title: Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives.
abstract: The sudden death of a young, apparently fit and healthy person is amongst the most challenging scenarios in clinical medicine. Sudden cardiac death (SCD) is a devastating and tragic outcome of a number of underlying cardiovascular diseases. While coronary artery disease and acute myocardial infarction are the most common causes of SCD in older populations, genetic (inherited) cardiac disorders comprise a substantial proportion of SCD cases aged 40 years and less. This includes the primary arrhythmogenic disorders such as long QT syndromes and inherited cardiomyopathies, namely hypertrophic cardiomyopathy. In up to 30% of young SCD, no cause of death is identified at postmortem, so-called autopsy-negative or sudden arrhythmic death syndrome (SADS). Management of families following SCD begins with a concerted effort to identify the cause of death in the decedent, based on either premorbid clinical details or the pathological findings at postmortem. Where no cause of death is identified, genetic testing of deoxyribonucleic acid extracted from postmortem blood (the molecular autopsy) may identify a cause of death in up to 30% of SADS cases. Irrespective of the genetic testing considerations, all families in which a sudden unexplained death has occurred require targeted and standardized clinical testing in an attempt to identify relatives who may be at-risk of having the same inherited heart disease and therefore also predisposed to an increased risk of SCD. Optimal care of SCD families therefore requires dedicated and appropriately trained staff in the setting of a specialized multidisciplinary cardiac genetic clinic.
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia Sydney Medical School, University of Sydney, Sydney, Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia c.semsarian@centenary.org.au.
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia Sydney Medical School, University of Sydney, Sydney, Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: Ingles
authors.affiliation: Heart Centre, Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications*; D001344:Autopsy / Q000379:methods; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D042241:Early Diagnosis; D059472:Exome; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007400:Interprofessional Relations; D018810:Magnetic Resonance Angiography; D010348:Patient Care Team; D010375:Pedigree; D014057:Tomography, X-Ray Computed; D055815:Young Adult
keywords: Genetics; Molecular autopsy; Multidisciplinary care; Postmortem; Specialized clinic; Sudden cardiac death