Von Hippel-Lindau Syndrome: VHL Gene Deletion/Duplication

Condition Description

VonHippel-Lindau syndrome (VHL syndrome) is characterized by hemangioblastomas ofthe brain, spinal cord, and retina; renal cysts and clear cell renal cellcarcinoma; pheochromocytoma; and endolymphatic sac tumors. Cerebellarhemangioblastomas may be associated with headache, vomiting, and gaitdisturbances or ataxia. Retinal hemangioblastomas may be the initialmanifestation of VHL syndrome and can cause vision loss. Renal cell carcinomaoccurs in about 40% of individuals with VHL and is the leading cause ofmortality. Pheochromocytomas can be asymptomatic but may cause sustained orepisodic hypertension. Endolymphatic sac tumors can cause hearing loss ofvarying severity, which can be a presenting symptom.

Thediagnosis of VHL syndrome is suspected in individuals with characteristiclesions including hemangioblastomas, renal cysts and renal cell carcinoma,pheochromocytoma, and endolymphatic sac tumors. The clinical diagnosis of VHLsyndrome is established in a simplex case (an individual with no known family history of VHL syndrome) presenting with two or more characteristic lesions or in an individual with a positive family history of VHL syndrome in whom one or more of the following diseasemanifestations is present: retinal angioma, spinal or cerebellarhemangioblastoma, pheochromocytoma, multiple pancreatic cysts, epididymal orbroad ligament cystadenomas, multiple renal cysts, or renal cell carcinomabefore age 60 years.

VHL is the only gene known to be associated with VHL syndrome. Molecular genetictesting of the VHL gene detects mutations in nearly 100% of affected individuals. Approximately 72% of VHL mutations are point mutations detected bysequence analysis. Approximately 28% of VHL mutations are partial or completegene deletions detectable by gene-targeted CGH array. VHL syndrome is inheritedin an autosomal dominant manner. Approximately 80% of individuals with VHL syndrome have an affected parent and about 20% have VHL syndrome as the result of a de novo gene mutation.The manifestations and severity of the disease are highly variable both withinand between families, even among those with the same mutation.

Click here for the GeneTests summary on this condition.

Genes (1)


This test is indicated for:

  • Confirmation of a clinical diagnosis of VHL in individuals who have tested negative for sequence analysis
  • Individuals at-risk for VHL due to family history who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient\'s clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the VHL gene by sequencing is available (UV) and is required before deletion/duplication analysis.
  • Prenataltesting is available to individuals who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

How to Order