Ordering Recommendation

Detect pathogenic RASA1 and EPHB4 variants. Confirm diagnosis in individuals with findings suggestive of capillary malformation-arteriovenous malformation syndrome types 1 and 2.

Mnemonic
CMAVM PAN
Methodology

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

Performed

Sun- Sat

Reported

Within 1 month

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 (EPHB4 and RASA1) Sequencing and (RASA1) Deletion/Duplication:
Characteristics:
Multifocal, randomly distributed, capillary malformations (CM) of the skin 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 EBHB4 pathogenic variants.
Incidence:
Estimated at 1 in 20,000 for CM-AVM1 and 1 in 12,000 for CM-AVM2.
Inheritance:
Autosomal dominant; approximately one-third of RASA1 pathogenic variants are de novo.
Penetrance: 90-95 percent.
Cause:
Pathogenic RASA1 and EPHB4 variants.
Clinical Sensitivity:
Not well-established, but at least 65 percent.
Methodology:
Bidirectional sequencing of all coding regions and intron-exon boundaries of the EPHB4 and RASA1 genes; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large RASA1 deletions/duplications.
Analytical Specificity and Sensitivity:
99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants and deep intronic variants will not be detected. Large deletions/duplications will not be detected in EPHB4. The breakpoints of large RASA1 deletions/duplications will not be determined.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81479

Components
Component Test Code* Component Chart Name LOINC
3001133 CMAVM Specimen
3001134 CMAVM 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
  • Capillary Malformation-Arteriovenous Malformation1
  • Capillary Malformation-Arteriovenous Malformation2
  • CM-AVM type 1
  • CM-AVM type 2
  • CM-AVM2
  • CMAVM1
  • EPHB4
  • RASA 1 related disorders
  • RASA1
Capillary Malformation-Arteriovenous Malformation (EPHB4 and RASA1) Sequencing, and (RASA1) Deletion/Duplication