Abstract
Congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal ECG and by a high risk of life-threatening arrhythmias. Disease prevalence is estimated at close to 1 in 2,500 live births.The two cardinal manifestations of LQTS are syncopal episodes, that may lead to cardiac arrest and sudden cardiac death, and electrocardiographic abnormalities, including prolongation of the QT interval and T wave abnormalities. The genetic basis of the disease was identified in the mid-nineties and all the LQTS genes identified so far encode cardiac ion channel subunits or proteins involved in modulating ionic currents. Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3, SCN5A, SCN4B) cause the disease by prolonging the duration of the action potential. The most prevalent LQTS variant (LQT1) is caused by mutations in the KCNQ1 gene, with approximately half of the genotyped patients carrying KCNQ1 mutations.Given the characteristic features of LQTS, the typical cases present no diagnostic difficulties for physicians aware of the disease. However, borderline cases are more complex and require the evaluation of various electrocardiographic, clinical, and familial findings, as proposed in specific diagnostic criteria. Additionally, molecular screening is now part of the diagnostic process.Treatment should always begin with β-blockers, unless there are valid contraindications. If the patient has one more syncope despite a full dose β-blockade, left cardiac sympathetic denervation (LCSD) should be performed without hesitation and implantable cardioverter defibrillator (ICD) therapy should be considered with the final decision being based on the individual patient characteristics (age, sex, clinical history, genetic subgroup including mutation-specific features in some cases, presence of ECG signs – including 24-hour Holter recordings – indicating high electrical instability).The prognosis of the disease is usually good in patients that are correctly diagnosed and treated. However, there are a few exceptions: patients with Timothy syndrome, patients with Jervell Lange-Nielsen syndrome carrying KCNQ1 mutations and LQT3 patients with 2:1 atrio-ventricular block and very early occurrence of cardiac arrhythmias.
Highlights
The congenital long QT syndrome (LQTS) is a relatively uncommon but important clinical disorder
Treatment should always begin with β-blockers, unless there are valid contraindications
The clinical manifestations of the disease are rather dramatic as they involve syncopal episodes, which often result in cardiac arrest and sudden death and usually occur in conditions of either physical or emotional stress in otherwise healthy young individuals, mostly children and teenagers
Summary
The congenital long QT syndrome (LQTS) is a relatively uncommon but important clinical disorder. The data published in 1991 [66] were updated in 2004 to include 147 LQTS patients who underwent LCSD during the last 35 years [65] These patients constituted a very high risk group, as witnessed by the fact that 99% were symptomatic, that their mean QTc was very long (563± 65 ms), that 48% had a cardiac arrest and especially that 75% continued to have syncope despite full-dose β-blockers. The identification of the genetic defect responsible for the disease in a family is important allowing to identify all affected family members at risk for life-threatening cardiac arrhythmias, even those with a normal QTc (silent http://www.ojrd.com/content/3/1/18 mutation carriers). The addition of oral chronic therapy with mexiletine (200 mg b.i.d.) produced a major shortening of QTc by over 100 ms persisting over time. (Reprinted from ref. [78] with permission from Elsevier)
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