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von Hippel-Lindau disease

Pathology: 1) angiomatosis 2) polycystic kidney disease 3) associated neoplasms a) medulloblastoma b) pheochromocytoma c) hemangioblastoma (CNS) - cysts &/or tumors (benign or malignant) may develop around the hemangioblastomas - mean age earlier than renal cell carcinoma [5] d) hemangioma (spinal cord, adrenal, lung,liver) e) angioma (retina) - mean age earlier than renal cell carcinoma [5] f) cyst (pancreas, kidney) g) pancreatic adenocarcinoma h) islet cell tumor - pancreatic neuroendocrine tumor i) renal cell carcinoma (mean age 44 years) [5] j) epididymal cystadenoma VHL type molecular defect clinical manifestation type 1 HIF1-alpha (u) hemangioblastomas, decreased risk of Pheo, RCC type 2A HIF1-alpha (u) hemangioblastomas. Pheo. low risk of RCC type 2B HIF1-alpha (u) hemangioblastomas, Pheo, high risk of RCC type 2C IF1-alpha (d) Pheo only HIF1-alpha (u): upregulation of HIF1-alpha HIF1-alpha (d): retains ability for degrade HIF1-alpha RCC: renal cell carcinoma Pheo: pheochromcytoma Genetics: 1) autosomal dominant 2) mutation in the VHL gene (3p25-26) Clinical manifestations: - nervous system a) headaches b) gait & balance impairment c) dizziness d) weakness of the limbs e) visual impairment f) hypertension Complications: 1) blindness 2) permanent brain damage 3) death Management: 1) varies according to the location & size of tumor(s) & associated cyst(s) 2) surgery or radiation for CNS tumor(s) when symptomatic 3) prognosis a) depends on the location & complications of tumor(s) b) prognosis is improved with early treatment c) death is usually caused by complications of brain tumors or renal cell carcinoma 4) belzutifan (Welireg) FDA-approved to treat cancers associated with von Hippel-Lindau disease

Related

von Hippel-Lindau disease tumor suppressor [VHL] gene

General

hereditary neoplastic syndrome; cancer susceptibility syndrome

Database Correlations

OMIM 193300

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2399
  2. Kaelin WG. Molecular basis of the VHL hereditary cancer syndrome. Nature Reviews Cancer 2:673-82, 2002 PMID: 12209156
  3. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
  4. Bankhead C FDA Approves First Drug for Von Hippel-Lindau-Associated Tumors. Objective response or stable disease in 100% of renal cell carcinomas. MedPage Today August 13, 2021 https://www.medpagetoday.com/hematologyoncology/renalcellcarcinoma/94034
  5. NEJM Knowledge+
  6. NINDS Von Hippel-Lindau Disease (VHL) Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Von-Hippel-Lindau-Disease-VHL-Information-Page