The congenital long QT syndromes from genotype to phenotype: clinical implications

The long QT syndrome (LQTS) is a genetic disorder responsible for many sudden deaths before age 20. The identification of several LQTS genes, all encoding cardiac ion channels, has had a major impact on the management strategy for both patients and family members. Genotype‐guided therapy allows more effective individually tailored therapy. Therapeutic options, including β‐blockers, left cardiac sympathetic denervation, and implantable defibrillators are discussed for patients of known and of unknown genotype. The recent identification of modifier genes which amplify the effect of an LQTS mutation may change the approach to risk stratification.

[1]  Dan M Roden,et al.  KCNH2-K897T Is a Genetic Modifier of Latent Congenital Long-QT Syndrome , 2005, Circulation.

[2]  P. Schwartz.  Management of long QT syndrome , 2005, Nature Clinical Practice Cardiovascular Medicine.

[3]  P. Schwartz,et al.  Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations: Characteristic T-U–Wave Patterns Predict the KCNJ2 Genotype , 2005, Circulation.

[4]  Arthur J Moss,et al.  25th anniversary of the International Long-QT Syndrome Registry: an ongoing quest to uncover the secrets of long-QT syndrome. , 2005, Circulation.

[5]  S. Priori,et al.  Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. , 2004, JAMA.

[6]  S. Priori,et al.  CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism , 2004, Cell.

[7]  S. Priori,et al.  Association of Long QT Syndrome Loci and Cardiac Events Among Patients Treated With β-Blockers , 2004 .

[8]  D. Tester,et al.  Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. , 2004, Heart rhythm.

[9]  S. Priori,et al.  Left Cardiac Sympathetic Denervation in the Management of High-Risk Patients Affected by the Long-QT Syndrome , 2004, Circulation.

[10]  M. Sanguinetti,et al.  Compound Mutations: A Common Cause of Severe Long-QT Syndrome , 2004, Circulation.

[11]  E. Kaufman,et al.  Location of Mutation in the KCNQ1 and Phenotypic Presentation of Long QT Syndrome , 2003, Journal of cardiovascular electrophysiology.

[12]  Carlo Napolitano,et al.  How Really Rare Are Rare Diseases?: , 2003, Journal of cardiovascular electrophysiology.

[13]  Calum A MacRae,et al.  Risk stratification in the long-QT syndrome. , 2003, The New England journal of medicine.

[14]  A. Gramolini,et al.  Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death , 2003, Nature.

[15]  R. Gow.  Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. , 2001, Circulation.

[16]  G. Breithardt,et al.  Life-threatening Arrhythmias Genotype-phenotype Correlation in the Long-qt Syndrome : Gene-specific Triggers for Genotype-phenotype Correlation in the Long-qt Syndrome Gene-specific Triggers for Life-threatening Arrhythmias , 2022 .

[17]  Wojciech Zareba,et al.  Spectrum of ST-T–Wave Patterns and Repolarization Parameters in Congenital Long-QT Syndrome: ECG Findings Identify Genotypes , 2000, Circulation.

[18]  S. Priori,et al.  Evidence for a Cardiac Ion Channel Mutation Underlying Drug‐Induced QT Prolongation and Life‐Threatening Arrhythmias , 2000, Journal of cardiovascular electrophysiology.

[19]  W Haverkamp,et al.  Gene-specific differences in the circadian variation of ventricular repolarization in the long QT syndrome: a key to sudden death during sleep? , 2000, Italian heart journal : official journal of the Italian Federation of Cardiology.

[20]  S. Priori,et al.  Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. , 2000, Circulation.

[21]  D. Tester,et al.  Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. , 1999, Mayo Clinic proceedings.

[22]  S. Priori,et al.  Low penetrance in the long-QT syndrome: clinical impact. , 1999, Circulation.

[23]  R. Hauer,et al.  Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). , 1999, Journal of the American College of Cardiology.

[24]  W. Allan,et al.  Long QT Syndrome , 1998, Pediatrics.

[25]  S. Priori,et al.  Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. , 1998, The New England journal of medicine.

[26]  G. Breithardt,et al.  KCNE1 mutations cause Jervell and Lange-Nielsen syndrome , 1997, Nature Genetics.

[27]  P. Coumel,et al.  A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome , 1997, Nature Genetics.

[28]  M. Sanguinetti,et al.  Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel , 1996, Nature.

[29]  Jacques Barhanin,et al.  KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current , 1996, Nature.

[30]  S. Priori,et al.  Differential response to Na+ channel blockade, beta-adrenergic stimulation, and rapid pacing in a cellular model mimicking the SCN5A and HERG defects present in the long-QT syndrome. , 1996, Circulation research.

[31]  P. Schwartz,et al.  Multiple mechanisms of Na+ channel--linked long-QT syndrome. , 1996, Circulation research.

[32]  Carlo Napolitano,et al.  Erratum: Long QT syndrome patients with mutations on the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: Implications for gene-specific therapy (Circulation (1995) 92 (3381-3386)) , 1996 .

[33]  G. Landes,et al.  Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias , 1996, Nature Genetics.

[34]  S. Priori,et al.  Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. , 1995, Circulation.

[35]  A. Moss,et al.  ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. , 1995, Circulation.

[36]  A. George,et al.  Molecular mechanism for an inherited cardiac arrhythmia , 1995, Nature.

[37]  Arthur J Moss,et al.  SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome , 1995, Cell.

[38]  E. Green,et al.  A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome , 1995, Cell.

[39]  P. Schwartz,et al.  Effect of calcium channel block on the wall motion abnormality of the idiopathic long QT syndrome. , 1994, Circulation.

[40]  S. Priori,et al.  Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome. , 1994, Circulation.

[41]  Peter J. Schwartz,et al.  Diagnostic Criteria for the Long QT Syndrome An Update , 1993, Circulation.

[42]  M. Leppert,et al.  The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. , 1992, The New England journal of medicine.

[43]  P. Schwartz,et al.  Unsuspected Echocardiographic Abnormality in the Long QT Syndrome: Diagnostic, Prognostic, and Pathogenetic Implications , 1991, Circulation.

[44]  A. Moss,et al.  Stress and sudden death. The case of the long QT syndrome. , 1991, Circulation.

[45]  P. Schwartz,et al.  Mapping of body surface potentials in patients with the idiopathic long QT syndrome. , 1986, Circulation.

[46]  P. Schwartz,et al.  Idiopathic long QT syndrome: progress and questions. , 1985, American heart journal.

[47]  P. Schwartz.  THE RATIONALE AND THE ROLE OF LEFT STELLECTOMY FOR THE PREVENTION OF MALIGNANT ARRHYTHMIAS , 1984, Annals of the New York Academy of Sciences.

[48]  H. L. Stone,et al.  Effects of Unilateral Stellectomy upon Cardiac Performance during Exercise in Dogs , 1979, Circulation research.

[49]  A. Malliani,et al.  The long Q-T syndrome. , 1975, American heart journal.

[50]  Ward Oc.  A NEW FAMILIAL CARDIAC SYNDROME IN CHILDREN. , 1964 .

[51]  O. C. Ward.  A NEW FAMILIAL CARDIAC SYNDROME IN CHILDREN. , 1964, Journal of the Irish Medical Association.

[52]  A. Jervell,et al.  CONGENITAL DEAF‐MUTISM, FUNCTIONAL HEART DISEASE WITH PROLONGATION OF THE Q‐T INTERVAL, AND SUDDEN DEATH , 1999, American heart journal.