Key Points
Disease summary:
Inherited channelopathy characterized by elongated QT intervals on electrocardiogram (ECG), caused by delayed ventricular repolarization in the myocyte.
Increased propensity to syncope, polymorphous ventricular tachycardia (torsade de pointes), T-wave abnormalities, and sudden death. Unexplained seizures can also be an atypical presentation.
Family history (in addition to above characteristics):
Sudden cardiac death
Sudden infant death syndrome
Congenital deafness
Hereditary basis:
LQTS exhibits predominantly autosomal dominant inheritance, meaning there is a 50% chance of a child inheriting the disease causing mutation from a parent.At least 12 genes have been implicated in LQTS, though the majority families have a mutation in KCNQ1, KCNH2 and SCN5A which cause LQT1, LQT2, and LQT3, respectively.There is variability of expression, even amongst family members with the same mutation.
Differential diagnosis:
It is important to distinguish the hereditary forms of the syndrome from environmental (acquired) causes including QT interval prolonging therapies (ie, antiarrhythmic agents), myocardial ischemia, alternative cardiomyopathies, hypocalcemia and hypothyroidism.
Diagnostic Criteria and Clinical Characteristics
| EGC features | Points |
|---|---|
| QTc >450 ms (males), >470 ms (females)a | 3 |
| Torsade de pointes | 2 |
| T-wave alternans | 1 |
| Notched T wave in three leads | 1 |
| Decreased heart rate for age (below second percentile) | 0.5 |
| Clinical history | |
| Syncope | |
| With stress | 2 |
| Without stress | 1 |
| Congenital deafness | 0.5 |
| Family history | |
| Unexplained sudden cardiac death <30 years among immediate family members | 0.5 |
| And the absence of | |
| |
| Probability of LQTS | |
| • Low | ≤1 |
| • Intermediate | 2-3 |
| • High | ≥4 |
Jervell and Lange-Nielsen syndrome (JNLS): characterized by congenital sensorineural hearing loss and long QTc interval, inherited in an autosomal recessive manner (KCNQ1 or KCNE1)
Brugada syndrome: characterized by rapid polymorphic ventricular tachycardia or ventricular fibrillation and sudden death, inherited in an autosomal dominant manner (SCN5A).
Timothy syndrome (LQTS with syndactyly): characterized by cardiac abnormalities (LQTS and/or structural defects), variable syndactyly of fingers or toes, facial anomalies and neurologic symptoms (autism, seizures, mental retardation), caused by de novo alterations in CACNA1C.
Andersen-Tawil syndrome (ATS): characterized by muscle weakness, ventricular arrhythmias, prolonged QT interval, facial and limb anomalies, caused by alterations in KCNJ2.
