Clinical Utility

Long QT syndrome (LQTS) is characterized by QT prolongation and T wave abnormalities on electrocardiogram (EKG) that predisposes individuals to life-threatening arrhythmias. The condition manifests primarily through syncope, cardiac arrest, and sudden cardiac death, with symptoms often triggered by emotional or physical stress. Cardiac events are most common from the preteen years through the 20s, though they can occur from infancy through middle age. LQTS exhibits incomplete penetrance for EKG changes and symptoms, with some genetically affected individuals showing normal QTc intervals on baseline EKG. The prevalence is estimated at 1:2,500. LQTS is predominantly inherited in an autosomal dominant manner, with pathogenic variants in KCNQ1, KCNH2, and SCN5A accounting for most genetically confirmed cases. Some rare forms show autosomal recessive inheritance, including Jervell and Lange-Nielsen syndrome (associated with congenital deafness) and TRDN-related LQTS-catecholaminergic polymorphic ventricular tachycardia (CPVT) overlap syndrome. Both sequence variants and copy number variants have been reported as causative. The diagnostic yield of this panel will vary based on the clinical phenotype of the patient and is expected to be approximately 75%.