SYMPTOMS
LQTS may be diagnosed in an asymptomatic individual on a routine ECG, as a part of family screening of a patient with LQTS or in asymptomatic individual presenting with syncope or resuscitated sudden death during or following exercise or stress or swimming in a young person.
Misdiagnosis of LQTS as epilepsy, particularly “familial epilepsy,” is common. Seizures following exertion, or arousal in the postpartum period , and during sleep, must raise the suspicion of LQTS.
Diagnosis of Long QT Syndrome
The diagnosis is usually made on clinical grounds. If the presentation is with syncope or resuscitated sudden cardiac death, the ECG shows QTc prolongation and the T-wave morphology is frequently abnormal. QT prolongation due to drugs or biochemical imbalance (low potassium, calcium or magnesium), hypothermia and myocardial disease must be excluded.
Features suggesting arrhythmic syncope include collapse associated with exercise, sudden emotional stress or loud noise, and physical injuries indicating failure to make protective movements when falling – particularly facial injury. Syncope associated with swimming is due to LQTS until proven otherwise.
Syncope secondary to pain or nausea or syncope preceded by nausea is more commonly 1. The implantable digital loop recorder (“reveal device”) can be valuable in detecting or excluding arrhythmia at time of syncope if others tests are inconclusive.
Family history: If Long QT syndrome is suspected, your doctor will ask a very detailed family history which looks for a history of syncope or sudden unexplained death at a young age in a close relative. Directed questioning is essential, with a family tree being drawn. The history of unexpected drowning in a strong swimmer, or road traffic accidents on a straight road are suggestive of a possible arrhythmic cause. Familial epilepsy and sudden infant death are also suspicious. Any sudden unexpected natural death with a negative post-mortem should trigger a family investigation for LQTS.
Family screening: ECGs should then be obtained on all first-degree relatives. Up to one third of asymptomatic gene mutation carriers have QTc values within the normal range. QTc values of 0.44 sec or more are treated as suspicious. Values below 0.41 sec are uncommon in gene carriers. The length of the QT interval is linked to the risk of syncope and sudden death, but all gene carriers are at an increased risk, and can still pass on the mutation to 50% of their children.
Genetics and Long QT syndrome
LQTS is most commonly inherited in an autosomal dominant manner and is sometimes called Romano- Ward syndrome. A single mutation in any one of the LQT1 through LQT13 genes results in this autosomal dominant form of LQTS. Each child of an affected parent has a 50% chance of inheriting a disease-causing gene mutation.
The commonest genotypes are types 1 and 2 (about 40 % each); about 8% are type 3. In each, a dysfunctional cardiac cell channel results in prolongation of the cardiac repolarization, and thus the QT interval. With current genetic techniques all 13 LQTS genes are screened and the genetic test result may identify the pathogenic mutation (in about 70% of LQTS patients) or the test may be negative or inconclusive in about 30% of LQTS patients. If a pathogenic mutation is found genetic testing is offered to all family members irrespective of their QT intervals as some 30% of LQTS gene carriers have normal QT intervals (concealed LQTS) and are able to pass on the genetic mutation and rarely, develop symptoms.
Studies of the three commonest genotypes (Types 1, 2 and 3) have shown that the life-threatening cardiac events (syncope or sudden death) tend to occur under specific circumstances in a gene-specific manner, and may have characteristic T wave morphologies.
Knowing the genetic type allows advice regarding life style modification to avoid precipitating factors, eg swimming and exertion in LQT1 and avoidance of sudden noise or alarm in LQT2.
