Ordering Recommendation

Acceptable initial test to confirm a suspected diagnosis of von Hippel-Lindau syndrome. Preferred test to confirm a suspected diagnosis of VHL-associated polycythemia.

Mnemonic
VHL FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Varies

Reported

7-14 days

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 Solution A or B).

Specimen Preparation

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

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval
Interpretive Data

Background Information for von Hippel-Lindau (VHL) Sequencing:
Characteristics of von Hippel-Lindau (VHL) Syndrome:
Retinal, cerebellar or spinal hemangioblastoma; renal cell carcinoma; pheochromocytoma; endolymphatic sac tumors; pancreatic endocrine tumors, and hemangiomas of adrenals, lungs, and liver.
Characteristics of Congenital Polycythemia:
Increased serum erythropoietin levels and hemoglobin concentrations during normoxia causing increased red blood cell mass; associated with increased mortality from thrombotic and hemorrhagic vascular complications.
Incidence of VHL Syndrome:
1 in 36,000 Caucasian births.
Incidence of Congenital Polycythemia:
Rare worldwide; endemic in Chuvash region of central Russia.
Inheritance of VHL Syndrome:
Autosomal dominant; de novo pathogenic variants occur in 20 percent of VHL cases.
Inheritance of Congenital Polycythemia:
Autosomal recessive.
Penetrance for VHL Syndrome:
Nearly complete by age 65.
Cause:
Pathogenic germline VHL gene variants.
Clinical Sensitivity:
89 percent for VHL syndrome, approximately 20 percent for congenital polycythemia.
Methodology:
Bidirectional sequencing of the VHL coding regions and intron-exon boundaries.
Analytical Sensitivity and Specificity:
99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants, deep intronic variants, and large deletion/duplications will not be detected. This assay is not designed to detect somatic variants associated with malignancy. Test result may be impacted if the patient has had an allogeneic stem cell transplantation.

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

81404

Components
Component Test Code* Component Chart Name LOINC
2002971 VHL FGS Specimen
2002972 VHL Sequencing 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
  • Chuvash Polycythemia
  • Congenital Polycythemia
von Hippel-Lindau (VHL) Sequencing