Ordering Recommendation

Detect pathogenic EPHB4 variants. Confirm diagnosis in individuals with findings suggestive of capillary malformation-arteriovenous malformation syndrome type 2.

Mnemonic
EPHB4 FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Sun-Sat

Reported

Within 2 weeks

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval
Interpretive Data

Background Information for Capillary Malformation-Arteriovenous Malformation 2 (EPHB4) Sequencing:
Characteristics of Capillary Malformation-Arteriovenous Malformation (CM-AVM):
Multifocal, randomly distributed, capillary malformations (CM) that may be associated with a fast-flow lesion (arteriovenous malformations [AVM] or arteriovenous fistula). Fast-flow lesions in the skin, muscle, bone, or central nervous system can cause life-threatening complications such as bleeding, congestive heart failure, or neurological consequences. Capillary malformation-arteriovenous malformation syndrome type 1 (CM-AVM1) is caused by RASA1 pathogenic variants; capillary malformation-arteriovenous malformation syndrome type 2 (CM-AVM2) is caused by EPHB4 pathogenic variants.
Incidence:
Estimated at 1 in 20,000 for CM-AVM1 and 1 in 12,000 for CM-AVM2.
Inheritance:
Autosomal dominant.
Penetrance: 90-95 percent.
Cause:
Pathogenic EPHB4 or RASA1 gene variants.
Gene Tested: EPHB4 only.
Clinical Sensitivity:
Not well established, at least 15 percent.
Methodology:
Bidirectional sequencing of all coding regions and intron-exon boundaries of the EPHB4 gene.
Analytical Specificity and Sensitivity:
99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants, deep intronic variants, and large deletions/duplications will not be detected. Variants in genes other than EPHB4 are not detected.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81479

Components
Component Test Code* Component Chart Name LOINC
3001130 CMAVM EPHB4 FGS Specimen
3001131 CMAVM EPHB4 FGS Interpretation
* 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
  • CM-AVM2, Capillary Malformation-Arteriovenous Malformation2
Capillary Malformation-Arteriovenous Malformation 2 (EPHB4) Sequencing