Other Symptoms of BHD

Currently, the only proven BHD symptoms are skin lesions, lung cysts, collapsed lungs and kidney cancer. As BHD is a rare disease, if only a few BHD patients develop another symptom it is very difficult to tell for certain if this symptom is caused by BHD or by coincidence. However, there are some symptoms that might be linked to BHD, so patients and their doctors should be aware of these:

  • Colon polyps and colon cancer
  • Parotid tumours
  • Thyroid nodules and thyroid cancer

In order to find out how many patients have other symptoms of BHD, we have designed a quick survey, which can be found here. Whether you have other symptoms or not, please do take two minutes to fill out the survey, if you can. It is completely anonymous, and the results will be posted here periodically.

The VHL Alliance have also launched the Cancer in our Genes International Databank which aims to gather information on the natural history of BHD to help researchers and clinicians to learn more about risk factors for patients.

Colon polyps and colon cancer

Some studies have found that colon polyps and cancer are symptoms of BHD, while other studies have found that they are not linked. Colon polyps and cancer are themselves quite common, meaning that a number of BHD patients may develop these symptoms by chance. This makes it very difficult to conclusively prove they are a symptom of BHD.

There is a region in the Folliculin gene called the polyC tract. Mutations in the polyC tract are very common and roughly half of BHD patients have a mutation in this region. There is some evidence that mutations in the polyC tract – but not other Folliculin mutations – might cause colon polyps and cancers, although this is not conclusive.

Parotid tumours

There have been at least eight cases of BHD patients developing parotid tumours. As BHD and parotid tumours are both so rare, it seems quite unlikely that eight patients have developed both by chance alone. For this reason, some BHD experts think that parotid tumours are a rare symptom of BHD, although there is still not enough evidence at the moment to statistically prove this link.

Thyroid nodules and cancer

Two studies have found that around half of BHD patients have thyroid nodules. However, neither study accounted for the fact that thyroid nodules are quite common in the general population. This means that at the moment we do not have enough information to know if these cases were coincidence, or if BHD causes thyroid nodules.

The BHD gene, Folliculin, has been shown to be lost in two thyroid tumours – one in a BHD patient, and in one sporadic case (i.e. the patient had thyroid cancer, but didn’t have BHD.) This suggests that BHD patients may have a very small risk of developing thyroid cancer, but again, at the moment there is not enough information to conclusively prove this.

 

Other symptoms

There have been a number of case studies that report BHD patients who have additional symptoms (listed below).

For the majority of these symptoms, there have only been one or two BHD patients who developed them. In other cases, like breast cancer or skin cancer, the disease is very common, meaning that we would expect some BHD patients to develop this symptom by chance. For these reasons, we think that these cases have been coincidence, and that BHD does not cause any of these symptoms.

This list is not exhaustive:

Cancers:

  1. Lung cancer
  2. Tonsillar cancer
  3. Thyroid cancer
  4. Breast cancer
  5. Skin cancer (melanoma and non-melanoma)
  6. Dermatofibrosarcoma protuberans
  7. Leiomyosarcoma (cutaneous)
  8. Gastric cancer
  9. Bladder cancer
  10. Uterine cancer
  11. Prostate cancer
  12. Leg sarcoma
  13. Hodgkin’s lymphoma
  14. Squamous cell carcinoma

Benign tumours:

  1. Oncocytic pituitary adenoma
  2. Astrocytoma
  3. Pheochromocytomas and other adrenal tumours
  4. Neurilemmomas
  5. Rhabdomyoma
  6. Collagenoma
  7. Cutaneous neurothekeoma
  8. Cutaneous leiomyoma
  9. Lipoma and angiolipoma
  10. Focal-cutaneous mucinosis
  11. Multinodular goiter
  12. Neural tissue tumour
  13. Trichoblastoma
  14. Connective-tissue nevus
  15. Vestibular schwannoma

Other:

  1. Ovarian cysts
  2. Chorioretinal lesions
  3. Aortic dissection
  4. Brain aneurysm/hematoma

Publication date: December 2014
Review date: December 2017