Lab Dept:

Anatomic Pathology

Test Name:

LONG QT SYNDROME PANEL

General Information

Lab Order Codes:

LQTS

Synonyms:

Ventricular Fibrillation with Prolonged QT interval; Romano-Ward syndrome (RWS); Jervell and Lange-Nielsen syndrome (JLNS)

CPT Codes:

81280 – Long QT syndrome gene analyses (eg, KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, ANK2); full sequence analysis
83891 x1 - Molecular diagnostics; isolation or extraction of highly purified nucleic acid, each nucleic acid type
83900 x1 – Molecular diagnostics; amplification, target multiplex, first 2 nucleic acid sequences
83901 x51 – Molecular diagnostics; amplification, target, multiplex, each additional nucleic acid sequence beyond 2
83904 x51 – Molecular diagnostics; mutation identification by sequencing, single segment, each segment
83909 x3 – Molecular diagnostics; separation and identification by high resolution technique, each nucleic acid preparation

Test Includes:

Sequencing of the entire coding regions of 12 genes: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C (through exon 44), CAV3, SCN4B, AKAP9 (only the KCNQ1 binding domains including the Ser1570 residue), and SNTA1.

Logistics

Test Indications:

Confirmation of a clinical diagnosis in symptomatic patients; Risk assessment for asymptomatic family members of a proband with LQTS; Differentiation of hereditary LQTS from acquired (non-genetic) causes of LQTS; Prenatal diagnosis in families with a known mutation.

Long QT syndrome (LQTS) is a cardiac disorder due to abnormal ion channel function characterized by prolongation of the QT interval on ECG. 75% of cases of LQTS are due to known genetic causes. It is associated with increased risk for syncope (unexplained fainting), ventricular arrhythmia and sudden cardiac death in young adults with normal heart structure.

LQTS is usually inherited in an autosomal dominant manner, and an affected individual with a disease-causing mutation has a 50% chance of transmitting this mutation to a child. Rarely, autosomal recessive inheritance has been described.

Reasons for referral:
1. Confirmation of a clinical diagnosis
2. Genetic counseling

Lab Testing Sections:

Anatomic Pathology - Sendouts

Referred to:

GeneDx, Inc. (GDX#: 360)

Phone Numbers:

MIN Lab: 612-813-6280

STP Lab: 651-220-6550

Test Availability:

Daily, 24 hours (Preferred draws are Sunday - Thursday as specimens can only be received at the reference lab Monday - Friday. Specimens collected Friday or Saturday will be held for shipment on Monday.)

Turnaround Time:

7 - 8 weeks

Special Instructions:

A signed consent form must be sent with any specimen. Forms can be obtained through the following link:
http://www.genedx.com/order-a-test/required-forms/

Specimen

Specimen Type:

Whole blood

Container:

Lavender top (EDTA) tube

Draw Volume:

2 - 5 mL blood

Processed Volume:

Same as Draw Volume

Collection:

Routine venipuncture, invert collection tube gently to mix

Special Processing:

Lab Staff: Do Not centrifuge. Blood specimen should remain in the original collection container. Store and ship at ambient temperature. Ship overnight at ambient temperature, using a cool pack in hot weather.
Note: Specimens may be stored at refrigerated temperatures for up to 7 days prior to shipping.

Patient Preparation:

None

Sample Rejection:

Mislabeled or unlabeled specimens

Interpretive

Reference Range:

No mutations detected. An interpretive report will be provided.

Critical Values:

N/A

Limitations:

Approximately 75% of individuals with a clinical diagnosis of idiopathic LATS are due to genetic causes. It is currently not known what percentage of these individuals would be expected to harbor a disease-causing mutation in the 12 genes tested for this panel. It is estimated that this panel would detect a disease-causing mutation in at least 70% of patients with LQTS. The technical sensitivity of this testing approach is estimated to be at 98% for mutations identifiable by sequence analysis. This sequencing test will not detect large chromosomal aberrations and deletions, insertions, or rearrangements greater than or equal to 5 base pairs. LQTS ExonArray DX analysis is specifically designed to detect partial or whole deletion/duplications of the 12 genes on the LQTS panel. Approximately 10% of patients with LQTS and no sequence abnormality in one of the common LQTS gene have been found to have a large deletion or duplication involving one of those genes.

Methodology:

Using genomic DNA, the entire coding region of 12 genes are sequenced using a novel sequencing-by-synthesis process that allows sequencing a large number of amplicons in parallel. For analysis, DNA sequence is assembled and compared to the published genomic reference sequences. The presence of any potentially disease-associated sequence variant(s) is confirmed by conventional dideoxy DNA sequence analysis. A reference library of up to 800 alleles is used to evaluate the frequency of novel sequence variants if indicated. If appropriate, testing of one affected relative or, if not available, of both biological parents, is performed to clarify variants of unknown significance at no additional charge.

References:

GeneDx, Inc. November 2012