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Doctor holding up a kidney ultrasound scan

Who can be referred for genetic testing for inherited kidney cancer?

7 Dec 2023

It is well known that mutations in certain genes can contribute to the development of kidney cancer. The Cancer Genome Atlas and studies investigating germline mutations in adult cancers identified mutations in 6 – 16% (i.e. 6 – 16  out of 100 people) of kidney cancer cases and there are now 15 genes associated with hereditary kidney cancer syndromes (including folliculin, the gene mutated in Birt-Hogg-Dubé Syndrome, BHD). Therefore, identification of individuals who require genetic risk assessment is important to ensure they receive the most appropriate care. However, clinical guidelines on genetic risk assessment are lacking.

Clear guidelines are required to aid clinicians to decide who requires further evaluation, how genetic counselling and testing should be performed, and which genes should be considered. This has particular relevance in the US where differing insurance policies on coverage for genetic testing can result in barriers in to access care. To address this a panel of experts, including Professor Gennady Bratslavsky (the invited speaker at our most recent Meet the Expert event), discussed several questions regarding genetic risk assessment for hereditary kidney cancer to develop consensus clinical guidelines.

A series of questions were curated by a steering committee and grouped into 5 different categories:

  1. Who should undergo genetic risk assessment?
  2. When should genetic risk assessment be performed?
  3. What testing should be performed?
  4. How should germline risk assessment be conducted?
  5. Testing in cases of isolated extrarenal lesions associated with known syndromes.

The questions were reviewed by the expert panel which included urologists, medical oncologists, genetic counsellors, clinical geneticists, and patient advocates. Uniform consensus was defined as ≥85% agreement.

Who should undergo genetic risk assessment?

Uniform consensus on who should undergo genetic risk assessment was reached for the following conditions:

  • Individuals with or without kidney tumours with a personal or family history of classic manifestations associated with hereditary kidney cancer (e.g. spontaneous pneumothorax).
  • Individuals with a 1st degree relative with a documented germline mutation (or 2nd degree relative if 1st degree is not available).
  • Individuals with kidney cancer who also have a 1st or 2nd degree relative with kidney cancer.
  • Individuals with kidney cancer that shows a specific histology (such as hybrid oncocytoma tumours - common in BHD).
  • Individuals with bilateral or multifocal kidney tumours (also common in BHD).

A consensus could not be agreed regarding a cut-off age for genetic risk assessment (i.e. whether age alone was a sufficient criterion to recommend genetic risk assessment in an individual with a kidney tumour).

When should genetic risk assessment be performed?

Uniform consensus on when genetic risk assessment should be performed was reached for the following condition:

  • Individuals with a renal lesion less than 3 cm and a strong suspicion for a hereditary cancer syndrome.

It was also agreed that a skin biopsy is not necessary to guide genetic risk assessment in individuals with a kidney tumour and skin lesions resembling those associated with a hereditary cancer syndrome. Other questions, including whether histologic diagnosis (i.e. confirming the type of kidney cancer) is required before genetic risk assessment was more contentious and the panel did not reach a consensus.

What testing should be performed?

A uniform consensus was agreed that multi-gene testing should be considered for individuals with more than 1 risk factor for a hereditary kidney cancer syndrome. It was generally agreed (although a uniform consensus was not reached) that individuals with a suspicion for a particular syndrome with a defined gene should be considered for single gene testing.

How should germline risk assessment be conducted?

Uniform consensus on how genetic risk assessment should be conducted was reached for the following conditions:

  • Genetic testing should not be performed without prior genetic counselling.
  •  Genetic counselling may be offered by a clinician with expertise in hereditary kidney cancer syndromes.
  • A telehealth consultation with a licensed counsellor is also sufficient before genetic testing.

Some of the panel agreed that a standardised video covering the essentials of pre-test genetic counselling was sufficient, however many were concerned about the lack of opportunity for discussion with a qualified provider.

Testing in cases of isolated extrarenal lesions associated with known syndromes

This category covered whether genetic risk assessment should be considered for individuals with no kidney lesions or a family history of kidney cancer but have other manifestations outside of the kidney associated with known hereditary kidney cancer syndromes. It was agreed that genetic testing should be offered in the following cases:

  • A single pheochromocytoma or paraganglioma (adrenal gland tumours).
  • A single endolymphatic sac tumour (a tumour in the ear strongly associated with Von Hippel-Lindau syndrome).
  • Uveal melanoma (cancer of the eye).
  • A single fumarate hydratase-deficient uterine fibroid (associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC)).
  • Regarding BHD, a consensus was not reached on individuals with a history of spontaneous pneumothorax or skin fibrofolliculomas.


Genetic testing is an important factor in assuring an individual receives appropriate care and management. For example, in BHD individuals should monitor their kidneys regularly and if the need for surgery arises, preserving as much of the kidney as possible is essential.  It was noted that there are several barriers to initiating genetic testing including a lack of confidence of clinicians to discuss the risks and benefits and interpretation and explanation of genetic testing results. Consensus guidelines on genetic risk assessment may aid clinicians to overcome the barriers of initiating genetic testing. As such, the findings here represent the first consensus guidelines for genetic risk assessment in hereditary kidney cancer. However, it should be noted that all panel members were from North America and therefore these findings may not necessarily be applicable worldwide. Additionally, the statements here are relatively broad given there are no previous consensus statements that can be further refined. Therefore, it is vital that follow up meetings are held to further refine and update these guidelines, particularly where there was a lack of consensus. 

At the BHD Foundation, we think this is a really important step towards implementing standardised guidelines for the diagnosis and management of BHD. We are happy to further advise on genetic counselling and testing and to help locate specialists in your area. Please do email us with all your BHD related queries.