Preferred test to confirm a suspected diagnosis of von Hippel-Lindau syndrome.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background Information for von Hippel-Lindau (VHL) Sequencing and Deletion/Duplication:
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: Greater than 99 percent for VHL syndrome, approximately 20 percent for congenital polycythemia.
Methodology: Bidirectional sequencing and multiplex ligation-dependent probe amplification (MLPA) of the entire coding region and intron-exon boundaries of the VHL gene.
Analytical Sensitivity and Specificity of Sequencing: 99 percent.
Analytical Sensitivity and Specificity of MLPA: 90 and 98 percent, respectively.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants and deep intronic variants will not be detected. Single exon deletion/duplications may not be detected due to probe location. Deletion/duplication breakpoints will not be determined. 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|
|2002966||VHL FGA Specimen|
- Congenital Polycythemia
- VHL (von Hippel-Lindau) Gene
- VHL sequencing and deletion/duplication assay