VHL should be suspected in individuals with or without a family history of VHL with:

  • Retinal angioma, especially in a young individual 
  • Multiple spinal or cerebellar hemangioblastoma, or a single hemangioblastoma diagnosed at age ≤50 years 
  • Adrenal or extra-adrenal pheochromocytoma 
  • Renal cell carcinoma diagnosed at age ≤40 years 
  • Multiple renal and pancreatic cysts 
  • Multiple neuroendocrine tumors of the pancreas 
  • Endolymphatic sac tumors 
  • Less commonly, multiple papillary cystadenomas of the epididymis or broad ligament 

VHL gene sequencing should be performed if VHL is suspected. We encourage all variants found in the VHL gene to be reported to CLINVAR.

If a gene mutation in VHL is identified as pathogenic, then the individual should be screened according to the guidelines. The first Von Hippel-Lindau syndrome (VHL) care pathway was recently published by a multidisciplinary team from the Netherlands [Wolters et al 2022].

With early detection, active surveillance and appropriate treatment, VHL disease has a better prognosis, or outcome, than many other tumor conditions and cancers. People with VHL as well as individuals who have a family history of VHL are encouraged to seek care from a healthcare team experienced with this complex disease. 

Belzutifan is in clinical development for the treatment of Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). Belzutifan is a first-in-class drug that is taken orally and works by selectively blocking the activity of the HIF-2α protein. HIF-2α plays a role in cancer cell survival, cell growth and blood vessel formation so by blocking this protein belzutifan is thought to slow down the worsening of the disease and improve symptoms. If licensed, belzutifan may offer an additional treatment option for patients with VHL disease-associated ccRCC. Belzutifan does not currently have Marketing Authorisation in the EU for any indication. Belzutifan was granted orphan drug designation by the EMA in August 2020 for the treatment of VHL disease. Belzutifan was FDA approved in August 2021 for VHL disease, and received marketing approval in the UK in September 2024. Discussions in Europe are still pending as of November 2024.