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Test ID: LQTGP Long QT Syndrome Multi-Gene Panel, Blood

Useful For

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of long QT syndrome (LQTS)

 

Establishing a diagnosis of a LQTS, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved

 

Identifying variants within genes known to be associated with increased risk for disease features and allowing for predictive testing of at-risk family members

Reporting Name

Long QT Syndrome Multi-Gene Panel,B

Specimen Type

Whole Blood EDTA


Advisory Information


Targeted testing for familial variants (also called site-specific or known mutation testing) is available for the genes on this panel. See:

-KVAR1 / Known Variant Analysis-1 Variant, Varies

-KVAR2 / Known Variant Analysis-2 Variants, Varies

-KVAR3 / Known Variant Analysis-3+ Variants, Varies

 

Call 800-533-1710 to confirm the appropriate test for targeted testing.



Necessary Information


1. Hereditary Cardiomyopathies and Arrhythmias: Patient Information (T725) is required, see Special Instructions. Testing may proceed without the patient information however it aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.



Specimen Required


Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.

Additional Information: Prior Authorization is available for this test. Submit the required form with the specimen.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Clinical 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’s treatment plan. For example, patients with an SCN5A pathogenic variant may not respond well to the typical first-line therapy of beta-blockers and may have a lower threshold for consideration of an ICD.

 

Genetic testing in LQTS is recommended and supported by multiple consensus statements to confirm the clinical diagnosis, assist with risk stratification, guide management, and identify at-risk family members. Even individuals with a normal QT interval may still be at risk for a cardiac event and sudden cardiac death and, thus, EKG analysis alone is insufficient to rule out the diagnosis and genetic testing is necessary to confirm the presence or absence of disease in at-risk family members. Pre- and posttest genetic counseling is an important factor in the diagnosis and management of LQTS and is supported by expert consensus statements.

Reference Values

An interpretive report will be provided.

Interpretation

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Reference

1. Online Mendelian Inheritance in Man. Retrieved June 2018. Available at www.omim.org/search?index=entry&sort=score+desc%2C+prefix_sort+desc&start=1&limit=10&search=Long+QT

2. Tranebjaerg L, Samson RA, Green GE: Jervell and Lange-Nielsen Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. Updated 2017 Aug 17. Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1405/

3. Alders M, Bikker H, Christiaans I: Long QT Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2003 Feb 20 (Updated 2018 Feb 8). Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1129/

4. Statland JM, Tawil R, Venance SL: Andersen-Tawil Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2004 Nov 22 (Updated 2015 Sep 3). Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1264/

5. Napolitano C, Splawski I, Timothy KW, et al: Timothy Syndrome. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle. 1993-2018. 2006 Feb 15 (Updated 2015 Jul 16). Accessed June 2018. Available at www.ncbi.nlm.nih.gov/books/NBK1403/

6. Barc J, Briec F, Schmitt S, et al: Screening for copy number variation in genes associated with the long QT syndrome: clinical relevance. J Am Coll Cardiol 2011;57(1):40-47

7. Priori SG, Wilde AA, Horie M, et al: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm 2013;10:12:1932-1963

8. Ackerman MJ, Priori SG, Willems S, et al: HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Heart Rhythm 2011;8:1308-1339

9. Pazoki R, Wilde AA, Bezzina CR: Genetic basis of ventricular arrhythmias. Curr Cardiovasc Risk Rep 2010;4:454-460

10. Wilde AA: Is there a role for implantable cardioverter defibrillators in long QT syndrome? J Cardiovasc Electrophysiol 2002;13(Suppl 1):S110-S113

Day(s) and Time(s) Performed

Wednesday; Varies

Analytic Time

4 weeks after prior authorization approved

CPT Code Information

81403

81404

81406 x 2

81407

81479

LOINC Code Information

Test ID Test Order Name Order LOINC Value
LQTGP Long QT Syndrome Multi-Gene Panel,B In Process

 

Result ID Test Result Name Result LOINC Value
36826 Gene(s) Evaluated 36908-2
36827 Result Summary 50397-9
36828 Result Details 82939-0
36829 Interpretation 59462-2
36956 Additional Information 48767-8
36957 Method 49549-9
36958 Disclaimer 62364-5
36830 Reviewed by 18771-6

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing Followed by Polymerase Chain Reaction (PCR) and Supplemental Sanger Sequencing

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Long QT Syndrome Multi-Gene Panel Prior Authorization Ordering Instructions in Special Instructions

3. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen.

Mayo Clinic Laboratories | Cardiology Catalog Additional Information:

mml-cardio-ngs