Von Hippel-Lindau Disease
Von Hippel-Lindau Disease (VHL) syndrome is an autosomal dominant familial cancer syndrome caused by mutations in the VHL tumor suppressor gene.
PrintVon Hippel-Lindau Disease (VHL) syndrome is an autosomal dominant familial cancer syndrome caused by mutations in the VHL tumor suppressor gene.
Affected individuals have a predisposition for developing bilateral renal cell carcinomas, pheochromocytomas, hemangioblastomas in the central nervous system, retinal angiomas, endolymphatic sac tumors, renal and pancreatic cysts. Currently, there is no cure for Von Hippel-Lindau Disease. Nevertheless, when the clinical diagnosis of VHL disease is confirmed by genetic testing, implementation of periodic screening has lead to early detection of tumors, timely intervention, and improved outcome for individuals affected with this disorder.
The Ambry Test: Von Hippel-Lindau Disease test offers concurrent gene sequence and deletion/duplication of the VHL gene. Mutations in the VHL gene can be detected in >99% of individuals affected with VHL syndrome. The Ambry TEST: VHL is capable of detecting >99% of all described VHL mutations.
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome caused by mutations in the VHL tumor suppressor gene.1 VHL syndrome has a prevalence of approximately 1 in 50,000 and an estimated incidence of 1 in 36,000 per year.2 Affected individuals have a predisposition for developing bilateral renal cell carcinomas, pheochromocytomas, hemangioblastomas in the central nervous system, retinal angiomas, endolymphatic sac tumors, renal and pancreatic cysts. Tumor formation, which usually corresponds to onset of disease, requires loss of both VHL alleles in the somatic tissue. The VHL gene encodes the VHL protein that is involved in multiple cellular processes, such as tumor suppression, oxygen-related gene expression, and protein assembly.3
VHL disease can be classified into two types depending on the risk of developing pheochromocytomas. Type 1 individuals have a low risk for pheochromocytomas while Type 2 individuals have a high risk. Type 2 is further subdivided into Type 2A (patients with a low risk of developing renal cell carcinoma), Type 2B (patients with a high risk of developing renal cell carcinoma), and Type 2C (isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma). Genotypically, Type 2 patients have missense mutations, while deletions or nonsense mutations are usually found in Type 1 individuals.4 Currently, there is no cure for von Hippel-Lindau disease. Nevertheless, when the clinical diagnosis of VHL disease is confirmed by genetic testing, implementation of periodic screening has lead to early detection of tumors, timely intervention, and improved outcome for individuals affected with this disorder.5
- Diagnostic testing for individuals known or suspected to have von Hippel-Lindau syndrome can assist in appropriate and effective treatment.
- Predictive testing for at-risk relatives with a known familial VHL mutation can identify those who may require enhanced surveillance.
This Ambry Test offers gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-3 of the VHL gene. Concurrent analysis for gross deletions/duplications of any exon is performed by multiplex ligation-dependent probe amplification. Specific mutation analysis for VHL mutations known to be in the family is also available.
Mutations in the VHL gene can be detected in >99% with VHL syndrome. 6, 7 The Ambry Test: von HippelLindau syndrome (VHL) is designed and validated to be capable of detecting ~99% of described mutations in VHL.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing for a VHL gene mutation is possible when the disease-causing mutation in an affected parent is known. Please call an Ambry Genetic Counselor to discuss your case.
Testing under 18 years of age: Since tumors associated with VHL disease have been reported in children as young as 4 years of age, testing of asymptomatic children is appropriate when the disease-causing mutation in an affected parent is known. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 2600 | VHL Gene Sequence Analysis | 83891x1, 83894x4, 83898x3, 83904x6, 83909x6, 83912x1 |
| 2604 | VHL Deletion / Duplication Analysis | 83891x1, 83894x1, 83900x1, 83901x7, 83909x1, 83912x1 |
| 2606 | VHL Sequencing and Deletion / Duplication | 83891x1, 83894x4, 83898x3, 83900x1, 83901x7, 83904x6, 83909x7, 83912x2 |
| Technique | Days |
|---|---|
| VHL Gene Sequence Analysis | 7-21 |
| VHL Deletion / Duplication Analysis | 7-14 |
| VHL Sequencing and Deletion / Duplication | 7-21 |
1 Latif F, Tory K, Gnarra J et al. Science. 1993; 260(5112):1317-20.
2 Maher ER, Iselius L, Yates JRW et al. J Med Genet. 1991; 28:443-7.
3 Gnarra JR, Tory K, Weng Y et al. Nat Genet. 1994; 7(1):85-90.
4 Maher ER, Webster AR, Richards FM et al. J Med Genet. 1996; 33:328-32.
5 Lonser RR, Glenn GM, Walther M et al. Lancet. 2003;361:2059-67.
6 Stolle C, Glenn G, Zbar B et al. Hum Mut. 1998;12:417-423.
7 Hoebeeck J, van der Luijt R et al. Lab Invest. 2005;85:24-33.