Preferred test to confirm a suspected diagnosis of von Hippel-Lindau syndrome.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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 mutations occur in 20 percent of VHL cases.
Inheritance of Congenital Polycythemia: Autosomal recessive.
Penetrance for VHL Syndrome: Nearly complete by age 65.
Cause: Pathogenic VHL gene mutations.
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 mutations and deep intronic mutations will not be detected. Deletion/duplication breakpoints 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|
|2002966||VHL FGA Specimen|
- Congenital Polycythemia
- VHL (von Hippel-Lindau) Gene
- VHL sequencing and deletion/duplication assay