Vascular Malformation NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81479

Cost

$3,000

Genes

• Bannayan-Riley-Ruvalcaba syndrome
• Cowden syndrome
• Capillary malformation-arteriovenous malformation
• Cerebral cavernous malformations
• Emberger syndrome Primary lymphedema with myelodysplasia
• Glomuvenous malformations
• Hennekam lymphangiectasia-lymphedema syndrome
• Hereditary hemorrhagic telangiectasia
• Hypotrichosis-lymphedema-telangiectasia syndrome
• Juvenile polyposis
• Lymphedema-distichiasis syndrome
• Microcephaly-capillary malformation syndrome
• Venous malformations
• Choanal atresia and lymphedema
• Hereditary lymphedema
• CLOVE syndrome

This panel consists of 21 genes that have been associated with circulatory and lymphatic vascular disorders including telangiectasia, lymphedema, and capillary malformations. The presentation of these disorders can be extremely variable. Inheritance is most often autosomal dominant with incomplete penetrance, but some forms of these conditions appear to follow an autosomal recessive pattern. The hereditary hemorrhagic telangiectasia syndromes may include nosebleeds, gastrointestinal bleeds, and potentially life-threatening brain, liver, or lung hemorrhages. Seizures and headaches may also occur although some individuals remain asymptomatic. Lymphedema syndromes show great variability and may improve or worsen with age, be unilateral or bilateral, and may include additional features of cellulitis, hydrocele, and skin or nail changes. Eye abnormalities, hearing loss, and developmental delays may occur in some of these disorders.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.