Von Hippel-Lindau syndrome


Gene Reviews

Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and cysts in many different parts of the body. Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination . Hemangioblastomas can also occur in the retina which may cause vision loss. People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.

Von Hippel-Lindau syndrome is also associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands. Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromo-cytomas are particularly dangerous if they develop during pregnancy. About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears and problems with balance. Without treatment, these tumors can cause sudden profound deafness.

Mutations in the VHL gene cause von Hippel-Lindau syndrome. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome.

We provide sequencing analysis for the VHL gene which is the only known gene to be associated with the forms of von Hippel-Lindau syndrome listed below.

Type OMIM Description
Type 1 193300 patients without pheochromocytoma; mutations grossly alter or lead to the absence of the proteins produced by the VHL gene.
Type 2A 193300 patients with pheochromocytoma and low risk of renal cell carcinoma; subtle or missense mutations of the VHL gene observed.
Type 2B 193300 patients with pheochromocytoma and high risk of renal cell carcinoma
Type 2C 193300 patients with familial pheochromocytoma without hemangioblastoma or renal cell carcinoma.

Purpose: Confirmation of Clinical Diagnosis

Methodology: Sequencing of entire coding region

Test Requisition: Sequencing Requisition

Specimen Requirements: 2-5 mL Blood- Lavender Top Tube

CPT Code: 81404 Cost: $400.00

Turn-around-time: 3-4 weeks

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1. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, Oldfield EH (2003). “von Hippel-Lindau disease”.  Lancet. 361(9374):2059-67. Review.

2. Maher ER, Neumann HP, Richard S (2011). “von Hippel-Lindau disease: a clinical and scientific review”.  Eur J Hum Genet.19(6):617-23.

3. Richard S, Graff J, Lindau J, Resche F (2004).”Von Hippel-Lindau disease”. Lancet. 363(9416):1231-4.

4. Sano T, Horiguchi H (2003). “Von Hippel-Lindau disease”. Microsc Res Tech. 60(2):159-64. Review.

5. Shehata BM, Stockwell CA, Castellano-Sanchez AA, Setzer S, Schmotzer CL, Robinson H (2008). “Von Hippel-Lindau (VHL) disease: an update on the clinico-pathologic and genetic aspects”. Adv Anat Pathol. 15(3):165-71.

6. Shuin T, Yamasaki I, Tamura K, Okuda H, Furihata M, Ashida S (2006). “Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment”. Jpn J Clin Oncol. 36(6):337-43. Review.




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1122 NE 13 Street, Suite 1400, Oklahoma City, OK 73104
Phone: (405) 271-3589 |Fax: (405) 271-7117 Email: Dr. Shibo Li

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