Capillary Malformation-Arteriovenous Malformation (EPHB4 and RASA1) Sequencing, and (RASA1) Deletion/Duplication
3001132
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.
ARUP Consult®
Disease Topics
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.

Statement C: 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
View Hotline History
Components
Component Test Code*Component Chart NameLOINC
3001133CMAVM Specimen
3001134CMAVM 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 view this test within the Laboratory Test Directory found at www.aruplab.com
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