Biomaterial Database

Genetics of sudden cardiac death syndromes. 2011

Nagesh Chopra, and Björn C Knollmann

Division of Cardiology, Department of Medicine, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

OBJECTIVE To survey recent developments in the field of genetics encompassing discovery of new candidate genes, new diagnostic strategies, and new therapies for sudden cardiac death (SCD) syndromes. RESULTS In addition to new mutations in known SCD genes, several novel genes not previously implicated in SCD causation have been found, particularly in long QT syndrome (e.g., KCNJ5, AKAP9, SNTA1), idiopathic ventricular fibrillation (e.g., DPP6, KCNJ8), dilated cardiomyopathy (e.g., NEBL), and hypertrophic cardiomyopathy (HCM; e.g., NEXN). Genetic SCD animal models have provided novel insights into the cellular mechanism and pathogenesis of nearly all the major SCD syndromes, which has led to several new drug therapies for patients with genetic arrhythmia syndromes (e.g., flecainide in catecholaminergic polymorphic ventricular tachycardia). Furthermore, genetic contributions to acquired heart diseases are increasingly being recognized. For example, a 21q21 locus is strongly associated with ventricular fibrillation after myocardial infarction. Near this locus is CXADR, a gene encoding a viral receptor implicated in myocarditis and dilated cardiomyopathy. Finally, common variants in cardiac ion channels and proteins likely contribute to common cardiac phenotypes. CONCLUSIONS Major strides have been made in uncovering new genes, mechanisms, and syndromes that have significantly advanced the diagnosis and treatment of genetic SCD disorders.

UI	MeSH Term	Description	Entries
D008133	Long QT Syndrome	A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.	Electrocardiogram QT Prolonged
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009202	Cardiomyopathies	A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).	Myocardial Disease,Myocardial Diseases,Myocardial Diseases, Primary,Myocardial Diseases, Secondary,Myocardiopathies,Primary Myocardial Disease,Cardiomyopathies, Primary,Cardiomyopathies, Secondary,Primary Myocardial Diseases,Secondary Myocardial Diseases,Cardiomyopathy,Cardiomyopathy, Primary,Cardiomyopathy, Secondary,Disease, Myocardial,Disease, Primary Myocardial,Disease, Secondary Myocardial,Diseases, Myocardial,Diseases, Primary Myocardial,Diseases, Secondary Myocardial,Myocardial Disease, Primary,Myocardial Disease, Secondary,Myocardiopathy,Primary Cardiomyopathies,Primary Cardiomyopathy,Secondary Cardiomyopathies,Secondary Cardiomyopathy,Secondary Myocardial Disease
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012307	Risk Factors	An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent.	Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D014693	Ventricular Fibrillation	A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.	Fibrillation, Ventricular,Fibrillations, Ventricular,Ventricular Fibrillations
D016757	Death, Sudden, Cardiac	Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)	Cardiac Sudden Death,Sudden Cardiac Death,Cardiac Arrest, Sudden,Sudden Cardiac Arrest,Arrest, Sudden Cardiac,Cardiac Arrests, Sudden,Cardiac Death, Sudden,Death, Cardiac Sudden,Death, Sudden Cardiac,Sudden Death, Cardiac
D017180	Tachycardia, Ventricular	An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).	Idiopathic Ventricular Tachycardia,Nonsustained Ventricular Tachycardia,Paroxysmal Supraventricular Tachycardia,Ventricular Tachyarrhythmias,Ventricular Tachycardia,Idiopathic Ventricular Tachycardias,Nonsustained Ventricular Tachycardias,Paroxysmal Supraventricular Tachycardias,Supraventricular Tachycardia, Paroxysmal,Tachyarrhythmia, Ventricular,Tachycardia, Idiopathic Ventricular,Tachycardia, Nonsustained Ventricular,Tachycardia, Paroxysmal Supraventricular,Ventricular Tachyarrhythmia,Ventricular Tachycardia, Idiopathic,Ventricular Tachycardia, Nonsustained,Ventricular Tachycardias
D053840	Brugada Syndrome	An autosomal dominant defect of cardiac conduction that is characterized by an abnormal ST-segment in leads V1-V3 on the ELECTROCARDIOGRAM resembling a right BUNDLE-BRANCH BLOCK; high risk of VENTRICULAR TACHYCARDIA; or VENTRICULAR FIBRILLATION; SYNCOPAL EPISODE; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac SODIUM CHANNEL alpha subunit.	Brugada ECG Pattern,Brugada Syndrome 1,Brugada Type ECG Pattern,Right Bundle Branch Block, ST Segment Elevation, and Sudden Death Syndrome,Sudden Unexplained Death Syndrome,Sudden Unexplained Nocturnal Death Syndrome,Sudden Unexplained Nocturnal Death Syndrome (SUNDS),ECG Pattern, Brugada