Ordering Recommendation

Consider for symptomatic individuals who meet 3 or 4 clinical criteria for HHT (recurrent epistaxis, mucocutaneous telangiectases, internal AVMs, and first-degree relative with HHT).

Mnemonic
HHT REFLEX
Methodology

Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

28-35 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Background Information for Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication
Characteristics:
Recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), and arteriovenous malformations (lung, brain, liver, spine).
Incidence:
1:5,000-10,000
Inheritance:
Autosomal dominant.
Penetrance:
Approaches 100 percent by age 40.
Cause:
Pathogenic variants in endoglin (ENG), activin A receptor type II-like 1 (ACVRL1 or ALK1), SMAD4 or other unidentified gene(s).
Clinical Sensitivity:
Approximately 85 percent
Methodology:
Bidirectional sequencing of the coding regions and intron-exon boundaries of ENG and ACVRL1, the 5' untranslated region of ENG, and a region of ACVRL1 intron 9 encompassing the CT-rich variant hotspot region. Multiplex ligation-dependent probe amplification (MLPA) of the coding regions of ACVRL1 and ENG.
Analytic Sensitivity:
99 percent for sequencing and 90 percent for MLPA.
Analytic Specificity:
99 percent for sequencing and 98 percent for MLPA.
Limitations:
Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplication cannot be determined. Regulatory region, intronic mutations, and mutations in genes other than ENG and ACVRL1 will not be detected.

Compliance Category

Laboratory Developed Test (LDT)

Note

If the results of this test do not explain the clinical scenario, then SMAD4 testing will be added. Additional charges apply.

Hotline History
N/A
CPT Codes

81405; 81406; 81479; if reflexed, add 81405; 81406

Components
Component Test Code* Component Chart Name LOINC
2009010 HHT Seq/DelDup Interpretation
2009011 HHT Seq/DelDup Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication with Reflex to Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication