Detect pathogenic RASA1 and EPHB4 variants. Confirm diagnosis in individuals with findings suggestive of capillary malformation-arteriovenous malformation syndrome types 1 and 2.
- Patient Preparation
- Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
- Capillary Malformation-Arteriovenous Malformation1
- Capillary Malformation-Arteriovenous Malformation2
- CM-AVM type 1
- CM-AVM type 2
- RASA 1 related disorders