Diagnostics

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Long QT Syndrome Panel

The Long QT Syndrome Panel is a comprehensive NGS panel that can be used to confirm a clinical diagnosis of Long QT syndrome or identify at-risk individuals. Long QT syndrome is characterized by a dysfunction of the heart’s electrical system which causes an lengthened QT wave on ECG and can lead to irregular heart rhythms. Individuals with long QT syndrome experience episodes of a specific form of irregular heartbeat called torsade de pointes (TdP) ventricular tachycardia which can lead to syncope (fainting), or, in severe cases, cardiac arrest or sudden death. The symptoms of long QT syndrome can present in childhood or adulthood, and most commonly occur during periods of intense exercise or emotional distress, although they can occur even when the patient is at rest.

Prevalence

The prevalence of long QT syndrome is estimated to be 1 in 2,000 individuals (Schwartz et al, 2009).

Included Disorders

This panel includes genes related to primary long QT syndrome as well as genes associated with disorders that include long QT syndrome as a feature. These disorders include:

  • Andersen-Tawil syndrome
  • Timothy syndrome
  • Jervell and Lange-Nielsen syndrome

Inheritance and Penetrance

Long QT syndrome is inherited in an autosomal dominant manner, with the exception of the subtype Jervell and Lange-Nielsen syndrome caused by mutations in the KCNE1 gene, and TRDN-related long QT syndrome, which are inherited in an autosomal recessive pattern.

Clinical Sensitivity

Disease causing mutations can be identified in approximately 80% of long QT syndrome cases (Ackerman et al, 2011). The Long QT syndrome panel includes all of the common genetic causes of long QT syndrome.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent intron/exon boundaries, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity of the assay is 99.5%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Unexplained cardiac arrest
  • Arrhythmia suggestive of long QT syndrome
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of long QT syndrome

Included Genes (15)

ANK2 KCNH2
CACNA1C KCNJ2
CALM1 KCNQ1
CALM2 SCN4B
CALM3 SCN5A
CAV3 SNTA1
KCNE1 TRDN
KCNE2

Additions to Long QT Panel

Emerging Evidence Genes (2)

Emerging evidence genes can also be added on to the Long QT Syndrome panel. These genes do not have a clear association with Long QT syndrome, but emerging evidence suggests that they may play a role in disease.

AKAP9
KCNJ5

References

  1. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace. 2011;13(8):1077-109.
  2. Goldenberg I, Horr S, Moss AJ, et al. Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J Am Coll Cardiol. 2011;57(1):51-9.
  3. Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348(19):1866-74.
  4. Schwartz PJ, Spazzolini C, Crotti L. All LQT3 patients need an ICD: true or false?. Heart Rhythm. 2009;6(1):113-20.