Long QT Syndrome
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Test Information

Long QT syndrome (LQTS) is a genetic cardiac disorder characterized by QT prolongation and T-wave abnormalities on electrocardiogram (EKG), which may result in recurrent syncope, ventricular arrhythmia, and sudden cardiac death. Romano-Ward syndrome (RWS), which accounts for the majority of LQTS, follows an autosomal dominant inheritance pattern and is caused by pathogenic variants in genes that encode cardiac ion channels or associated proteins. The diagnosis of RWS is established by the prolongation of the QTc interval in the absence of other conditions or factors that may lengthen it, such as QT-prolonging drugs or structural heart abnormalities. Clinical factors such as a history of syncope and family history also contribute to the diagnosis of RWS. RWS has an estimated prevalence of 1 in 3,000 individuals. Of the families who meet clinical diagnostic criteria for RWS, approximately 75% have known genetic causes, while approximately 25% have no detectable pathogenic variants in any of the genes known to cause RWS. Approximately 3% of RWS cases are the result of large deletions or duplications in KCNQ1 or KCNH2. Deletions/duplications have not been reported in the other genes implicated in RWS. Only about half of the individuals with a pathogenic gene variant associated with RWS have symptoms, usually one to a few syncopal spells, and thus many patients with this condition unfortunately present with sudden cardiac death as their first symptom. Cardiac events may occur any time from infancy through adulthood, but are most common from the preteen years through the 20s. Additionally, RWS is believed to account for approximately 10% to 15% of sudden infant death syndrome (SIDS) cases. In some cases, LQTS may be associated with congenital profound bilateral sensorineural hearing loss, known as Jervell and Lange-Nielsen syndrome (JLNS). JLNS is inherited in an autosomal recessive inheritance pattern and is caused by homozygous or compound heterozygous pathogenic variants in either KCNQ1 or KCNE1. Timothy syndrome (TS) is a multisystem disorder involving prolonged QT interval in association with congenital anomalies that may include hand/foot syndactly, structural heart defects, facial dysmorphology, and neurodevelopmental features. Ventricular tachyarrhythmia is the leading cause of death with an average age of death of 2.5 years. TS is inherited in an autosomal dominant manner and usually occurs as a result of a de novo heterozygous variant in the CACNA1C gene. Management strategies for LQTS include pharmacologic therapies, implantable cardioverter defibrillators (ICD), or other surgical interventions, and lifestyle restrictions such as avoidance of competitive sports or other triggers for cardiac events. In some cases, knowledge of the LQTS genotype may assist in tailoring an individual

Also known as: LQTS Gene Testing Blood, LQTS.

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