Canalopatias

Cardiac ChannelopathiesGenotype-Phenotype Relationships in Long QT SyndromeFigure 1: Congenital long QT syndrome (LQTS) comprises a distinct group of cardiac channelopathies characterized by delayedrepolarization of the myocardium, QT prolongation, and increased risk for syncope, seizures, and sudden cardiac death in the setting of a structurally normal heart and otherwise healthyindividualCongenital long QT syndrome (LQTS) comprises a distinct group of cardiac channelopathies characterized by delayed repolarization of the myocardium, QT prolongation, and increased risk for syncope,seizures, and sudden cardiac death in the setting of a structurally normal heart and otherwise healthy individual (Figure 1).(11,12) This repolarization abnormality almost always is without consequence,however rarely, when caught off guard by triggers such as exertion, swimming, emotion, or auditory stimuli the heart can spiral electrically out of control into a potentially life threatening andsometimes lethal dysrhythmia.(11) Though in most incidences the heart’s rhythm spontaneously returns to normal following an episode of syncope, 5% of untreated and unsuspecting LQTS individuals succumb to afatal arrhythmia as their sentinel event.LQTS is a genetically heterogeneous disorder most often inherited in an autosomal dominate mode. To date, hundred of mutations have been identified withapproximately 75% of clinically robust LQTS due to mutations in 5 genes: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6) encoding for critical cardiac ion-channel subunits that areresponsible for the orchestration of the cardiac action potential (Figure 2).(13)Since diagnosing his first patient with LQTS and carving out a postdoctoral fellowship in molecular genetics to identifythat patient’s LQTS-causing mutation (Pediatric Research 1998), Dr. Ackerman’s laboratory has investigated the genetic basis for over 600 unrelated patients and over 1500 family members referred...