Announcing our 2022 Grant Holders – Part 1

At the BHD Foundation we are passionate about driving research into Birt-Hogg-Dubé syndrome (BHD). Through the Myrovlytis Trust, we have funded over £6 million of research into BHD since 2007. We are now pleased to announce the first 2 projects we funded in 2022.

Understanding how Kidney Cancer in BHD develops

We awarded funding to Professor Masaya Baba (Kumamoto University, Japan) for a PhD scholarship to investigate BHD kidney cancer. BHD is associated with changes in the gene folliculin (FLCN). Everyone has 2 copies of the FLCN gene, however changes in only one of them gives rise to many of the features seen in BHD. However, for kidney cancer to develop it is thought that changes in the second copy of FLCN are required (often known as a “second hit”). Masaya’s team will investigate what happens in cells lacking FLCN. They will identify pathways and specific proteins that are essential for cells lacking FLCN to survive and form tumours. In the longer term, these proteins could be targets for the development of new therapies to treat kidney cancer in BHD.

Watch Masaya describe his work in this short video or find out more. A transcript of the video is also available.

Natural Killer Cell Therapy for Kidney Cancer

Our second grant holder, Professor Mark Lowdell (University College London, UK) is interested in the interplay between the immune system and cancer. His group have a particular focus on a type of cell called natural killer (NK) cells. These can directly kill target cells, including cancer cells. However, many cancers develop strategies to avoid recognition by the immune system. Mark’s group have developed a drug to activate NK cells to make them better at killing cancer cells. We have awarded funding to Mark’s team for a 1-year project looking at whether people with kidney cancer have NK cells that can be enhanced with this drug. They hope to identify which patients will benefit most from this drug and use the data to design and support a clinical trial. Although this project isn’t looking at kidney cancer in people with BHD, we are still excited by the prospect of a new type of treatment for kidney cancer. Future work could be done to look at this type of treatment in BHD kidney cancer.

Watch Mark describe his work in this short video or find out more. A transcript of the video is also available.

At the BHD Foundation we are driven to find new treatments and eventually a cure for BHD. We have just launched our grant funding round for 2023. Find out more including what we fund and how to apply. We also welcome informal enquiries by email.

Birt-Hogg-Dubé Syndrome in Individuals with Smith-Magenis Syndrome

Birt-Hogg-Dubé syndrome (BHD) is characterised by skin lesions, lung cysts, collapsed lungs and an increased risk of kidney cancer. It is associated with changes in the gene folliculin (FLCN). Our genes are organised into thread-like structures called chromosomes. Humans have 23 pairs of chromosomes. The FLCN gene is found on chromosome 17, in a specific region called “17p11.2”. Another condition, called Smith-Magenis syndrome (SMS) is also associated with a deletion of this 17p11.2 region.

Unlike BHD, SMS is not normally inherited and occurs in every 1 in 15,000 – 25,000 people. Individuals with SMS often have a distinct facial appearance and varying degrees of developmental delay and intellectual disability. People with SMS also have distinct behaviours such as sleep disturbance and hyperactivity. However, this condition is distinct from BHD, as this 17p11.2 region also contains a gene called RAI1. Research has shown that a loss of RAI1 is responsible for most of the features seen in SMS. As such, people with BHD do not get the features seen in SMS. However, people with SMS may also be missing a FLCN gene and therefore may be at risk of the features seen in BHD. As the most serious complication of BHD is kidney cancer, people with BHD should get regular scans to monitor their kidneys. So far, cancer has only been occasionally reported in people with SMS and individuals do not have regular kidney scans.

To date, there have only been a few reports of people with SMS having features of BHD. A recent survey*, carried out by PRISMS (Parents and Researchers Interested in Smith-Magenis Syndrome) looked at the prevalence of BHD features in people with SMS. Of 117 respondents, 7 people reported at least one feature of BHD. 5 people had a collapsed lung, and 2 people had fibrofolliculomas. There were no cases of kidney cancer. However, most people in this survey were under 30 years of age. It is thought that the average age of onsent of kidney cancer in people with BHD is 50.

A recent paper* has summarised 4 cases of BHD in people with SMS and provides recommendations for cancer screening. All cases were confirmed to be lacking a copy of the FLCN gene. The first case decribed a patient (aged 50) who was found to have hybrid oncocytic tumours in both their kidneys and underwent surgery to remove these tumours. They did not have any skin lesions or lung cysts. The second patient was diagnosed with SMS aged 37. Aged 45, they were found to have diffuse B cell lymphoma. Scans also showed they had lesions on their kidney and further tests revealed this to be chromophobe kidney cancer. They had no skin or lung features of BHD. The third patient, aged 25, had lung cysts and skin lesions consistent with BHD. They had no kidney tumours. The last patient was aged 42 and had surgery to remove a 3.6 cm tumour that was confirmed to be chromophobe kidney cancer. They had no skin lesions or lung cysts.

In summary, this recent report identified 4 cases of people with SMS who also had features of BHD. 3 of these had kidney tumours. The authors of this study recommend screening for kidney cancer in adults with SMS in line with the current BHD guidelines, where kidney scans are recommended at least every 3 years starting from age 20.  Most of the studies in SMS so far have been done in children and adolescents and so it is still unclear how common features of BHD in SMS are, considering the features in BHD typically appear in adulthood. Further work, particularly long-term studies are required to fully characterise BHD in people with SMS.

*Unfortunately these papers are not open access. Please email us at contact@bhdsyndrome.org if you have any questions.

Identification of a New BHD Syndrome-Like Condition

Birt-Hogg-Dubé syndrome (BHD) is a rare inherited condition associated with changes in the gene folliculin (FLCN). Most people are diagnosed through a genetic test to check for changes in the FLCN gene. However, a small proportion of people do not have a detectable change (or variant) in FLCN. This group of people can still be diagnosed with BHD based on the presence of clinical criteria. Features of BHD include skin lesions called fibrofolliculomas, lung cysts and collapsed lungs and an increased risk of kidney cancer.

A recent study described an individual who was initially diagnosed with BHD. They came to the clinic aged 33 with multiple skin lesions. These included fibrofolliculomas on the face and chest, skin tags, lesions in their mouth and multiple lipomas. They had no lung cysts but had one small kidney cyst. They were diagnosed with BHD based on the presence of fibrofolliculomas, but genetic testing did not find a FLCN variant. There was a family history of lipomas, other skin lesions and kidney cancer. By the age of 48, they had more than 50 lipomas surgically removed and many more still present. The patient then consented to whole exome sequencing to search for changes in other genes that might be responsible for these features. A variant in a gene called PRDM10 was found. The same change was also found in affected family members.

The authors of the study then looked at the function of PRDM10 in cells. They made cell lines (cells grown in a laboratory) that contained the PRDM10 variant. PRDM10 is proposed to function as a transcription factor. Transcription factors function to turn genes on and off to control which proteins are produced. The particular mutation in PRDM10 that this family was found to have is in a part of the protein important for turning on target genes. In a previous study in mice, it was shown that PRDM10 can turn on the FLCN gene. In this study, the authors found the same effect in human cells. This was confirmed in cells with the PRDM10 variant where the levels of FLCN were almost undetectable. They compared the cells with the PRDM10 variant to cells that were lacking FLCN and found many of the same changes. This included an increase in a protein called GPNMB which has been found in high levels in kidney tumours from people with BHD.

Linking their work in the lab back to the features found in the patient and their family, the authors suggested that the fibrofolliculomas and kidney cancer could be due to the reduction in FLCN. However, there were no lung cysts present which is a common feature of BHD. It was suggested that perhaps the levels of PRDM10 are lower in the lung than the skin and kidney. The levels of FLCN in cells may be under control of multiple different transcription factors. Lipomas were a very common feature in this patient and their family. It is yet to be discovered how the PRDM10 variant drives the formation of these. PRDM10 is likely to control other genes aside from FLCN. Although lipomas have been found in people with BHD, the authors thought that a loss of FLCN was unlikely to be responsible for this.

In summary, the authors of this study have identified a new syndrome with overlapping features of BHD. However, more work is needed to fully understand the role of PRDM10 in the development of this new condition. Identification of other families with the same variant in PRDM10 would also strengthen the data provided in this study. At the BHD Foundation, we found this study interesting as it increases our knowledge of BHD and similar conditions. We look forward to seeing future work on this, and potentially the identification of new BHD-like conditions.

BHD Foundation 2022 Highlights

As we put together a calendar of events for 2023, we reflect on our achievements from the last year. After the relaunch of the BHD Foundation in 2021, we were keen to drive the charity’s efforts to fund research and provide support for people with Birt-Hogg-Dubé syndrome (BHD) in 2022 and beyond. We are proud of what we achieved last year and would like to thank everyone who contributed to our work.

Here, we share our 2022 highlights.

Infographic timeline describing the work done at the BHD Foundation in 2022. This is repeated in the text in the blog.

Events

We kickstarted 2022 with a ‘Meet the Expert’ event hosted by the BHD Foundation team. We shared our achievements from 2021 and set out our plans for 2022. We then held 2 further ‘Meet the Expert’ events. In April, Dr Ed Cowen (NIH, USA) shared his work on BHD and the skin. We also held a panel discussion in July on BHD, genetics and pre-implantation genetic testing/IVF.

Join us for our next Meet the Expert with Professor Lisa Henske on February 1st. Lisa will be talking about her work on BHD and lung cysts. Get your free ticket now.

Our biggest event of 2022 was the BHD Community Symposium. This symposium was the first deliberately designed to be accessible to all members of the community. We were thrilled to welcome people with BHD and their families alongside clinicians and researchers to further connect the community. We were delighted to have over 200 people registered from 22 countries across 5 continents for this virtual event. Read the research and patient-focused highlights.

Research and Conferences

One of our proudest achievements of 2022 was launching the BHD Syndrome International Registry (BIRT) at the end of March. We launched BIRT with the aim of driving forward research and giving people with BHD the opportunity to participate in research. We now have over 200 people registered and we look forward to this growing over the coming years. Read our 6 month registry update.

We took part in several conferences this year to raise awareness of BHD among researchers and clinicians. We developed a BHD awareness leaflet (a printable version is also available) that was shared on a virtual platform at the European Respiratory Society Congress and WONCA, the general practitioner conference. We were also delighted to be able to present our work on BIRT at the European Conference on Rare Diseases and the 4th International Conference on Rare Diseases.

We were also delighted to announce our grant holders from 2021 in February. We also held another grant funding round in 2022 and will be announcing our new grant holders very soon. Research is an integral part of our work at the Myrovlytis Trust and BHD Foundation. Advancing research into BHD is important so that we can better understand it and develop new treatments

Raising Awareness and Social Media

2022 was also a busy year for getting involved in social media and raising awareness of BHD to the wider community. In January, we took part in Medics 4 Rare Diseases ‘Mystery Monday’ which educates future doctors about rare diseases. We also took part in Rare Disease Day and led the World Pneumothorax Day campaign. We got to share personal stories of BHD on these days including Lea’s story ‘From Lung Collapse to Ironman’ and Joanna’s story  ‘Married on a Mountain with a Collapsed Lung’. We look forward to taking part in these events in 2023 and sharing more of your inspiring stories.  

Read more about our work raising awareness of BHD in 2022.

Fundraising

We were thrilled to launch our fundraising programme this year. We held a Prize Draw this year and raised over £650 towards a new BHD Foundation website. There are several other ways you can get involved and we would love to hear your fundraising ideas!

We would like to say a huge heartfelt thanks to everyone who got involved with us in 2022 and can’t wait to continue building and supporting the BHD community in 2023 and beyond.

BHD 2022 Survey Results: You Said – We Did

At the end of 2022, we sent out a survey to the BHD community about our work at the BHD Foundation. We wanted to make sure you had a say in the projects that we prioritise in 2023.  In this blog, we summarise some of the common themes and ideas highlighted by the survey and how we are addressing them.

Connecting with Others

You said:

  • You would be interested in meeting other people with BHD.
  • You would be interested in face-to-face conferences.
  • You enjoy the Meet the Expert sessions and are most interested in hearing from lung and kidney experts and BHD researchers.
  • You would like a list of BHD specialists in different countries.

We did:

  • We direct all new BHD patients to the BHD patient led Facebook group where they can share experiences, ask for advice and connect with others.
  • We have confirmed a date for the 2023 BHD Research Symposium. This year’s event will be aimed at clinicians and researchers. We also encourage patients to attend as an opportunity to learn more about the latest research. The symposium will be hosted both in person and online. More details about this will be announced soon.
  • We have confirmed a date for the first Meet the Expert Session of 2023. On Wednesday 1st February we will be joined by Lisa Henske. She will be talking about her research into BHD and lung cysts. Register now.
  • We have an interactive map where you can search for BHD experts. We have also added an option to download a list of BHD experts in different countries.

We are planning:

  • To explore creating a ‘virtual coffee’ morning. These virtual meetings will be a platform where people with BHD can meet and share their experiences. If you are interested in helping with these sessions get in touch with us at contact@bhdsyndrome.org.
  • To host a dedicated patient conference every other year following the success of the BHD Community Symposium in 2022. This will include opportunities to connect with researchers, clinicians and other people with BHD.

Medical Records and Research

You said:

  • You would like to hear more about current research.
  • You would like to be involved with research.
  • You would like to see more research in the following areas:
    • non-kidney cancers
    • genetics
    • skin
  • You said that research reports are not always accessible to people who do not have research backgrounds. 
  • You would like information on the difference between cysts and tumours.
  • You would like all your medical records to be in one place.

We did:

  • We have a weekly blog post. We blog about the majority of new BHD research that is published.
  • We launched the BHD Syndrome International Registry (BIRT) which will help to advance research into BHD. Anyone with a BHD diagnosis can take part and contribute to research. 
  • We established the first BHD patient advisory board. This year they will be involved in reviewing grant applications to ensure the research we fund is relevant and impactful for people with BHD.
  • We are currently funding several research projects into different aspects of BHD. This includes a project looking at BHD genetics and a project looking at the skin. We are in regular contact with our grant holders and will keep you up to date with these research projects.
  • We are PIF TICK accredited and complete a yearly assessment. This means that we have processes in place to ensure that any new resources we make are accessible to people with non-research backgrounds. This includes involving members of the BHD community (patients and experts) throughout the development and testing of new resources.  

We are planning:

  • To announce our 2022 grant holders very soon so you can find out more about our newly funded research.
  • To explore how best to support people to get involved with research.
  • To soon announce our 2023 research funding call.
  • To redesign the BHD website and include information on a range of topics based on your feedback.  For example, the difference between tumours and cysts. If you have anything you’d like to see on the new website let us know at contact@bhdsyndrome.org.   
  • To explore different platforms where you can upload medical records.

BHD Syndrome International Registry (BIRT)

You said:

  • You would like to know where you can find information about BIRT.
  • You would like to share the link to the BHD registry.
  • You have concerns about sharing personal information in the BHD registry.
  • You would like the registry to be available in multiple languages.
  • You would like more information on how to navigate BIRT and how the data is used for research.   

We did:

We are planning:

  • To write a FAQ on BIRT that will address all your questions. The blog will be published in February. Until then please contact us at contact@bhdsyndrome.org with any questions.

Awareness

You said:

  • It can be challenging to talk to family members about BHD.
  • We need to raise awareness of BHD among doctors.  

We did:

We are planning:

  • To present and exhibit at conferences to raise awareness of BHD among doctors.

We will continue to review the feedback as the year progresses and update you on our progress. Thank you to everyone who took part in the survey. We wish you all a wonderful start to the new year.

Happy Holidays!

The Myrovlytis Trust and BHD Foundation would like to say a massive thank you to everyone who has got involved with our work this year! We are very grateful to each of you for sharing your story, taking part in World Pneumothorax Day, attending our Meet the Expert events and our first every community-focused symposium. We look forward to seeing as many of you as possible at our 2023 events to raise awareness and drive forward research into BHD together.

We are always keen to receive your feedback about what you would like to see from us in the future. We would greatly appreciate it if you could complete this short survey and let us know what is important to you. The survey will close on Tuesday 3rd January. Take the survey now.

We also launched our fundraising programme this year and are extremely thankful to the community for helping us to raise money towards a new BHD website which we will be launching next year. We look forward to hearing your fundraising ideas in 2023.

Our offices will be closed from Friday 23rd December 2022 and will reopen on Tuesday 3rd January 2023. We will respond to any enquiries upon our return.

From all of us at the Myrovlytis Trust and BHD Foundation, we wish you a wonderful holiday season and a happy new year!

An Alternative to Surgery for BHD Kidney Cancer

Kidney cancer occurs in up to 1 in 3 people with Birt-Hogg-Dubé syndrome (BHD). Normally, any kidney tumours are surgically removed if they reach 3 cm in size. Surgeons will aim to preserve as much of the kidney as possible.  This is because people with BHD may need multiple surgeries. However, surgery may not always be the best option. For example, the tumours may be in a part of the kidney that is difficult to operate on or in which surgery would lead to reduced kidney function. Therefore, alternative options to surgery for BHD kidney cancer are needed. A report was published looking at the outcomes of people with BHD who underwent percutaneous thermal ablation (PTA) to treat their kidney cancer.

What is percutaneous thermal ablation?
PTA is a non-surgical procedure that uses extreme heat or cold to destroy cancer cells. It is used to treat many different cancers. However, it is not routinely used in the treatment of BHD kidney cancer. There are many types of PTA. The most common are called radiofrequency, microwave and cryoablation. The type you get may depend on the experience of the person carrying out the procedure as well as the size and location of the tumour.

What did the researchers do?

This study looked at anyone with BHD who underwent PTA between 2007 and 2021 under the Reference Centre of the National Network for Rare Cancers in Adult PREDIR in France. In this timeframe, 6 people with BHD were identified. 4 people had previous surgery on the same kidney and one person had their other kidney completely removed. A total of 19 tumours were treated across 14 PTA sessions. Most of these tumours were treated using radiofrequency PTA. One was treated using microwave PTA and another tumour was treated using cryoablation.

All the tumours were treated successfully. This means that there was no evidence of the tumour remaining or spreading after treatment during the follow-up period (an average of 74 months). 5 of the people treated had chronic kidney disease. There was a slight reduction in kidney function after PTA in these people. However, none of the people treated developed kidney failure or required dialysis.

What did they learn?

In this study, PTA was found to be a successful way of treating kidney cancer in people with BHD. PTA has both benefits and limitations compared with surgery. PTA can be carried out without the need for general anaesthetic. General anaesthetic can increase the risk for having a collapsed lung in people with lung cysts due to BHD. It also appears that multiple rounds of PTA can be carried out successfully. However, it should be noted that surgery can be more challenging after ablation.

PTA could be particularly relevant for people in which surgery might not be suitable. This includes the elderly or people with reduced kidney function. However, the number of people in this study was very small. A larger study that could directly compare the effectiveness of PTA with surgery would be warranted.

Take part in research

As BHD is a rare condition, it is often difficult to get enough people to take part in a study to be able to draw conclusions. We launched the BHD Syndrome International Registry to capture as much information about BHD as possible. Sign up to the registry now to help us speed up and drive forward research.

New Techniques to Understand BHD Kidney Cancer

Birt-Hogg-Dubé syndrome (BHD) is associated with an increased risk of kidney cancer. Currently, people with BHD should get their kidneys monitored regularly to check for tumours. If these tumours reach 3 cm, surgery is done to remove them. However, there may be some situations where surgery isn’t appropriate. Therefore, there is a need to develop new treatment strategies for kidney cancer in BHD. To do this, we need a good understanding of how kidney cancer develops in BHD. This includes knowing which type of kidney cell the cancer came from and how these cells differ in their gene expression patterns.

A study published earlier this year looked at different inherited kidney cancers at a single cell level. This means looking at the individual cells that make up the cancer. They did this by taking samples from kidney tumours that were being surgically removed. In this study, there was one chromophobe kidney cancer tumour and one hybrid oncocytic chromophobe tumour (HOCT) from people with BHD. They then split the tumour into individual cells and used a technique called RNA sequencing.  This technique tells us which genes are turned on or off in cells. Doing this at a single cell level (instead of the entire tumour) allows us to know what is happening in each cell. This is important because tumours are complex and made up of many different cell types. A “map” can be created from the RNA sequencing data, where each cell is placed based on which genes are turned on in that cell. The cell type can be identified based on which genes were found. Cells that have similar genes turned on will be close to each other on the map. On this map, the researchers found that cells from BHD kidney cancers were close to a type of kidney cell called collecting duct. This suggests that BHD kidney cancers may originate from this cell type.

Next, the researchers looked at which genes were turned on specifically in the different types of BHD kidney cancer. It is common to only know which type of kidney cancer you have after surgery to remove the tumour. However, it may be useful to know which type of kidney cancer you have before treatment as this may influence the treatment you get. For example, different types of kidney cancer grow at different rates and some are more likely to spread than others. The researchers found that different genes were turned on/off in chromophobe cancer vs HOCT. In the future, a test may be able to look for these genes to identify which type of cancer a person has. Of particular interest, the authors of the study also identified a gene called MET found at high levels in BHD kidney cancers compared with other kidney cancers. There are already MET inhibitors that are approved for treating cancer, including kidney cancer. Therefore, the use of these inhibitors should be investigated further in BHD kidney cancer.

Altogether, this study used the latest technologies to further understand inherited kidney cancers. We look forward to seeing more research to understand how kidney cancer develops and how it can be treated in the future.

Can I Fly with BHD? – Katty’s BHD Story

Katty was diagnosed with Birt-Hogg-Dubé syndrome (BHD) in 2019 and was advised not to fly by her doctors. Having been a travel artist and looking forward to exploring the world with her sons, this news was very difficult.

In 2022, Katty wrote to the BHD Foundation in search of more information about BHD. Based on discussions with BHD experts and results from published research we explained that we do not advise against flying and it’s an individual’s choice. Current research suggests that if 1000 people with BHD flew on a plane, 1 or 2 of them would have a lung collapse. Pleurodesis may reduce this risk.

Although you can fly with BHD, you should not fly if you have a collapsed lung. This is because it will likely make it worse. If you have any symptoms of a collapsed lung you should see a doctor immediately.  

We spoke to Katty about her experiences being diagnosed with BHD and the challenges she faced when trying to find information about flying.

Watch the full interview below or read the transcript.


Autumn Case Reports

Every few months we highlight some of the recent Birt-Hogg-Dubé syndrome (BHD) case reports. A case report is a detailed account of (normally) a single person’s diagnosis and treatment journey. Case reports are published in medical journals and are an opportunity for clinicians to learn about how different conditions may present.

In this blog we look at two cases of cancer in BHD patients. 

BHD is characterised by skin bumps (fibrofolliculomas), lung cysts, collapsed lungs and kidney tumours. The kidney tumours are normally slow-growing so with regular scans they can be monitored and removed if they reach 3cm. At the BHD Foundation, we often get asked if BHD is associated with any other cancer types. This is a difficult question as 1 in 2 people will get some type of cancer in their lifetime and most of these people do not have BHD.  Therefore, how do we determine if other cancers are caused by BHD or are unrelated?  

The case reports below describe two different types of cancer in people with BHD. A case study on its own cannot prove a link between BHD and a cancer. To find a link you need lots of data. This is where the BHD syndrome international registry (BIRT) comes in. BIRT is a patient-reported database where patients can upload information about their BHD. This data will feed into research and help answer vital questions. The reason case studies are still important is they can help researchers to identify areas of potential research.  

Cancer in the adrenal gland

The first case* described a 38-year-old man with a tumour on his left adrenal gland. The adrenal glands are two small glands that sit on top of the kidneys and produce hormones. Further investigations led to a formal diagnosis of a rare type of cancer called adrenal cortical carcinoma (ACC). In other words, cancer in the outer layer of the adrenal gland. He was treated with surgery and chemotherapy.

The next step for the clinicians was to find out why he developed this cancer. ACC is a rare cancer and is linked to genetic conditions including Li-Fraumeni syndrome. Therefore, they performed genetic testing. The test revealed a mutation in the gene folliculin (FLCN). Variants in this gene cause BHD. A diagnosis of BHD was further supported by the finding of skin bumps and lung cysts.

Once the diagnosis of BHD was confirmed, the doctors speculated on whether there could be a link between adrenal gland cancers and BHD. So far 5 cases of adrenal gland cancer have been reported in BHD patients including one other case of ACC.

Follicular Dendritic Cell Sarcoma

The next case discussed a 34-year-old man with low iron and blood in his stools. He had a camera test to check the inside of his bowels and they found a mass. He had surgery to remove the mass and was then diagnosed with a rare cancer called follicular dendritic cell sarcoma (FDCS). FDCS is a cancer that develops from specialised immune cells. It normally occurs in lymph nodes but can occur anywhere in the body including the digestive tract as seen in this case.

Next, the clinicians investigated the cause of his cancer. The patient had an extensive family history of cancer which suggested there may be a genetic component.  He was tested for several cancer-causing genes and had a positive FLCN mutation. Similar to the previous case, he was then found to have skin bumps to support a diagnosis of BHD.

This is the first case of FDCS to be reported in a BHD patient. It must be noted FDCS is very rare cancer with only 32 cases of FDCS in the digestive tract reported. The authors felt that it was unclear whether BHD was the cause of the FDCS or if it was just a coincidence that the patient had the mutation.  

Key messages

These case reports describe two rare cancers in people with BHD. However, as discussed above this does not mean that they are caused by BHD. As more data accumulates in the registry we can start to build a clearer picture of whether any other cancers are associated with BHD and if any other cancer screening is needed.

These cases also highlight the need for increased awareness of BHD. Both patients had skin bumps before their cancer diagnosis. However, neither of them had been investigated for BHD. However, it is promising to see FLCN included in genetic cancer screens. By being diagnosed with BHD, even if it had nothing to do with their symptoms, both patients will receive vital monitoring of their kidneys. This means if they do develop kidney cancer in the future it will be identified and treated as early as possible.

*Please note this paper is unfortunately not freely available. Please email contact@bhdsyndrome.org if you have any questions.