Acceptable initial test to confirm a suspected diagnosis of von Hippel-Lindau syndrome. Preferred test to confirm a suspected diagnosis of VHL-associated polycythemia.
Polymerase Chain Reaction/Sequencing
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2002971||VHL FGS Specimen|
|2002972||VHL Sequencing Interpretation|
- Chuvash Polycythemia
- Congenital Polycythemia