Presentation: Patient with cerebellar haemangioblastoma

A 37-year-old man is diagnosed with cerebellar haemangioblastoma. His sister was diagnosed with renal cell cancer one year ago aged 45. You wish to undertake genomic testing and are considering what constitutional (germline) and somatic (tumour) genetic testing is available and appropriate for him.

Constitutional (germline) testing

• All patients >60 years old diagnosed with cerebellar haemangioblastoma.
• All patients of any age diagnosed with ≥2 Von Hippel-Lindau (VHL)-related tumours (retinal angioma, spinal or cerebellar hemangioblastoma, adrenal or extra-adrenal pheochromocytoma, renal cell carcinoma, multiple renal and/or pancreatic cysts, endolymphatic sac tumours, papillary cystadenomas of the epididymis or broad ligament, neuroendocrine tumour of the pancreas).
• ≥1 VHL-related tumour and first-degree relative with ≥1 VHL-related tumour (where one of the tumours is cerebellar hemangioblastoma or retinal angioma).
• All patients >40 years old diagnosed with retinal angioma, or spinal or endolymphatic sac tumour.

Somatic (tumour) testing

• In the future, somatic (tumour) testing is likely to be expanded to include larger somatic gene panels. Ultimately, it is likely that paired somatic and constitutional (germline) whole genome sequencing will be performed.

• Consult the National Genomic Test Directory eligibility criteria to ensure your patient is eligible for testing. You can also refer to this spreadsheet of all available tests.
• For information on the genes that are included on different gene panels for constitutional (germline) testing, see the NHS Genomic Medicine Service signed-off panels resource.
• Decide which of the panels best suits the needs of your patient. For those in whom VHL is suspected and that meet eligibility criteria, the option is:
  • R225: Von Hippel-Lindau syndrome
  • VHL gene testing may also be offered as part of a broader renal cancer predisposition gene panel for those patients with renal cell cancer fulfilling eligibility (R224: Inherited renal cancer)
• A record of discussion (RoD) form is required. If you have not completed an RoD form before and/or do not have access to one, please review this Knowledge Hub article on how to complete an RoD form.
• Depending on the details you provide and the test that is chosen, a range of different genomic investigation techniques will be applied to your patient’s/their family’s (if appropriate) DNA. These tests include (but are not restricted to):
  • Single gene sequencing
  • Gene panel sequencing
  • MLPA
• For DNA-based tests (all the above listed tests), an EDTA sample is required. Please refer to your local Genomics Laboratory Hub for details of test request forms and where to send samples.

For clinicians

• HEE Genomics Education Programme: Von Hippel-Lindau syndrome factsheet
• NHS England: National Genomic Test Directory and eligibility criteria (note that somatic (tumour) tests are listed in the directory for cancer, while constitutional (germline) tests are listed in the directory for rare and inherited disease)

For patients

• VHL Alliance: Support and information for patients