Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication with Reflex to Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication
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).
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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).
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.
Laboratory Developed Test (LDT)
If the results of this test do not explain the clinical scenario, then SMAD4 testing will be added. Additional charges apply.
81405; 81406; 81479; if reflexed, add 81405; 81406
|Component Test Code*||Component Chart Name||LOINC|
|2009010||HHT Seq/DelDup Interpretation|
|2009011||HHT Seq/DelDup Specimen|