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.

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.

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.

BHD Community Symposium Feedback

The BHD Foundation was delighted to host the BHD Community Symposium online on October 8th, 2022. If you couldn’t attend, you can read our research report and our advocacy report. We will be making the recording available to all registered attendees very soon.

We asked attendees to complete a short survey at the end of the symposium to provide their feedback. This feedback will help to inform future events. We had 19 responses, 7 from researchers and/or clinicians and 12 from people with BHD. We were thrilled that everyone found the symposium useful and that they learned something new. We asked people to vote for their top 3 sessions. The most popular sessions were

1. Research Talks – we heard from researchers around the world discuss their work on BHD
2. Meet the Experts – we had 3 ‘rooms’ featuring a Q&A with skin, lung and kidney BHD experts
3. ‘BHD and Me’ – a patient-led panel discussion where people with BHD shared their lived experiences

Importantly, everyone thought that the research talks were clear. As this event was designed to be accessible for all members of the BHD community, this was a priority for us. However, the proportion of people who strongly agreed with the statement ‘The research talks were clear’ did differ between researchers/ clinicians and people with BHD. Over half (4/7) researchers/ clinicians strongly agreed that the research talks were clear. A quarter (3/12) people with BHD strongly agreed that the research talks were clear. Everyone else that provided feedback agreed with the statement. At future community-focused symposiums we will strive to improve this statistic.

We also asked 3 open questions:

1. What did you like about the BHD symposium?
2. How could the symposium have been improved?
3. What would you like to see at next year’s symposium?

The responses to the first question have been used to create the word cloud you can see in the poster below and we have included select responses at the end of this blog. When asked how the symposium could be improved, the overwhelming response was that you wanted more! There were requests for more research and longer research talks, more patient testimonies and more opportunities for networking. Another common response was accessing the symposium due to time differences. As a charity that supports people with BHD around the world, we understand that time differences can be challenging. We had over 200 people from 22 different countries registered for this year’s symposium. To reach as many people as possible we recorded the event. We are making the recording available to everyone who registered very soon to watch at your convenience.

When asked what you would like to see at next year’s symposium, again the response was that you wanted more! The feedback we got requested more research, sessions on the treatment of BHD and more panel discussions. There was also a request to feature more work from underrepresented countries. This year, we were delighted to have researchers from 8 different countries present their work. Next year, we hope to welcome even more researchers.

Luckily, our symposium next year will be held over 2 days on October 13th and 14th 2023. It will be taking place in London, UK but there will also be an option to join online. Although research-focused, everyone is still invited to attend. We will be announcing further details about next year’s symposium soon. To receive updates, please sign up to our newsletter.

Selected quotes from the feedback survey in response to ‘What did you like about the BHD symposium?’:

“Breakout session enabled me to “meet” other scientists I know from reading but not to talk with. Before the end of the conference I was exchanging emails with one and may well ultimately do research with (just like after and in-person conference).”

“Perfect organisation, not easy to blend a public of patients, clinicians and researcher so well!”

“The chance to speak to experts – since my diagnosis 4 years ago I have tried to get answers to questions but have been given the wrong advice or no response. So thank you so much.”

“It is hopeful to see research is happening and get answers to some of my questions as well as more information for practitioners.”

“I enjoyed the atmosphere of being taken serious and cared for, because most doctors here in Germany have never heard of this disorder. Thank you very much for letting me attend the symposium.”

“I liked hearing about kidney cancer surgery and learning something new every time, especially when presenters can present in a way we can understand as non experts.”

“Seeing how other people from various parts of the world are together with a common goal.”

BHD Community Symposium 2022 Report – Research

The first BHD Community Symposium was held on October 8th, 2022. We were delighted to have over 200 people registered from 22 countries across 5 continents for this virtual event. This year’s symposium was the first deliberately designed to be accessible to all members of the community throughout the entire event. We were thrilled to welcome people with Birt-Hogg-Dubé syndrome (BHD) and their families alongside clinicians and researchers.

There were a range of sessions from the latest research to a Q&A with BHD experts. We also held a session with members of the BHD community sharing their personal BHD stories. The opening talk featured our CEO, Anna Webb, in conversation with Sue Sherman, Director and CEO of the LAM Foundation. They spoke about the shared challenges faced by communities in the rare disease space and the importance of the patient voice when tackling them.

…it’s the voices, as we know, of our communities that really are vital to the progress of both research as well as improving treatment from rare diseases.” Sue Sherman

Raising awareness, connecting the community and inspiring the next generation of scientists were topics for discussion. There are so many things we can learn from other rare communities, but it is important to remember we are not alone. We need to work with other advocacy organisations such as the LAM Foundation to build our network and drive change. This conversation was a positive and inspiring way to start the symposium and we are extremely grateful to Sue for joining us.

BHD Research Updates

There were several sessions dedicated to the latest BHD research. To kickstart this session, we heard from Julia Thierauf, BHD community member, clinician and researcher. She gave an overview of the scientific process and how research works. Following on from this, we heard from some of our 2021 grant holders as well as researchers from around the world.

Understanding BHD

Many talks were focused around better understanding BHD as a condition and how it affects people. Bryndis Yngvadottir (UK) gave us an update on their work trying to better estimate the prevalence of BHD. BHD is associated with variations in the gene folliculin (FLCN). Looking at how many people have a FLCN variant can help us work out how common BHD is. Rates from the literature vary from around 1 in 3000 people to 1 in 500,000 people. The work presented here, looking at the 100,000 genomes project suggested that the prevalence of BHD may be closer to the 1 in 3000 people estimate.

Lore van Riel (The Netherlands) presented the need to raise awareness of BHD among doctors to improve diagnosis. BHD is the most common genetic cause of a collapsed lung. In people that have a collapsed lung for no obvious reason, BHD should be considered, especially if there is a family history. We also heard from Ortrud Steinlein (Germany) about the delay between first symptom appearance and diagnosis in BHD. We recently blogged about her work and how gender might affect diagnosis.

Liu Jie discussed their work in China to improve BHD diagnosis. They found the most common symptom was a collapsed lung. Very few people had symptoms in the skin or kidney. However, another study from a rare lung clinic in China showed a higher number of people with skin symptoms. More work needs to be done to understand any difference in symptoms between different ethnicities. A talk from Fiona Bruinsma (Australia), looked at the proportion of people with each symptom of BHD. They found that by age 70, over 9 in 10 people had symptoms in the skin and/or lungs.

Together, these projects will help us better understand how people are affected by BHD and inform diagnosis and management pathways.

Understanding Folliculin

It is vital to understand the cellular biology behind BHD. There is a lot of work being done to understand the biology of FLCN and how a loss of FLCN leads to the symptoms seen in BHD.

We heard from Ryosuke Jikuya (Japan) and Ye Yang (USA) who are both using state-of-the-art methods to look at kidney cancer in BHD at the molecular level. Their work will help us understand more about how kidney cancer develops and grows. It will pave the way for future work to develop new therapies for BHD-related kidney cancer. 

Damir Khabibullin (USA) spoke about their work looking at FLCN in the lung. Their data shows that loss of FLCN in lung cells called mesenchymal cells led to the formation of lung cysts. Understanding how lung cysts form could help inform future treatments for the lung.

Rob Wolthuis (The Netherlands) presented research identifying a new BHD-like syndrome. Their work identified the gene responsible for this new syndrome and found that it was a regulator of FLCN protein. This work expands our knowledge of how FLCN works in our cells as well as identifying a new condition related to BHD.

Treatments

Research was also presented on the treatment of BHD-related kidney cancer. Currently, the standard treatment is for any tumours to be removed by surgery when they reach 3 cm. However, there are some situations where surgery may not be appropriate. Sylvain Bodard (France) presented their work using a technique called percutaneous thermal ablation for the treatment of kidney cancer. They found this to be a safe and effective treatment for BHD-related kidney cancer.

We also heard from Dustin Armstrong (USA) who spoke about a new drug that may have benefit in treating BHD-related kidney cancer. This drug has already been tested in another condition called Pompe disease and has been found to be safe. They are now interested in pursuing research and collaborations to test their drug in BHD.

Summary

It is exciting to see the breadth and depth of research happening around the world into BHD. We were thrilled to be able to bring this research to the entire BHD community.

“The research talks were fascinating, highly informative and gives us all a lot of hope that significant advances are being made towards finding a cure and towards optimal management of BHD.”  Feedback from BHD Community Symposium attendee

Connecting all parts of the community is at the heart of the BHD Foundation. There is so much we can learn from each other, and it was heart-warming to be able to share different perspectives.

“I am getting to see patient perspectives for the first time, and simultaneously saw great cutting-edge research results. This leaves me with a lot of hope that we will one day soon be able to treat all patients efficiently, successfully with minimal invasive procedures.”  Feedback from BHD Community Symposium attendee

Our blog post next week will round-up our BHD Community Symposium report, focusing on the ‘Meet the Expert’ and ‘BHD and Me’ sessions.

If you registered for the event but couldn’t attend on the day, a recording of the event will be sent as soon as it is available. You can also still take part in the BHD raffle that was launched at the symposium. To receive the latest updates about events, sign up to our newsletter.

The BHD Syndrome International Registry – 6 Month Update

What is BIRT?

The BHD Syndrome International Registry (BIRT) is a patient registry that collects information on the diagnosis, symptoms and management of Birt-Hogg-Dubé syndrome (BHD). The overall mission of BIRT is to improve the quality of life of those living with BHD. We hope to achieve this through collecting data that will allow a consensus on diagnosis and management guidelines to be produced. Diagnosing BHD early is important to ensure that the condition is managed so that any kidney cancer is caught as early as possible.

However, for BIRT to be a success, we need as many people as possible to get involved. One of the major problems that slows down research into rare conditions is the lack of data. Through BIRT, we can provide that data to researchers to help them answer so many of the unknown questions about BHD. This is a chance for the community to come together to drive forward and speed up research into BHD.

Find out how to get involved below.

Who is currently involved in the registry?

There are currently 173 people registered from 18 countries around the world. Around 2 thirds of people registered are female and one third are male. However, we know that gender doesn’t affect who gets BHD. Therefore, we encourage you to spread the word to your family members so that they can get involved. Most people are aged between 55 and 60, however this ranges from age 20 to 85. You can also sign up on behalf of someone and complete their information by proxy.


What do we know so far?

Diagnosis

On average, people are diagnosed with BHD at age 44. However, the average age of first symptom is 30 years. This represents a huge gap between symptom and diagnosis. It also shows why we need more awareness of BHD to speed up diagnosis. Participants also reported the first time they contacted health services regarding symptoms of diagnosis of BHD. The average for this was 43 years. This suggests that people aren’t contacting their healthcare providers upon the first symptom of BHD. However, there are some caveats to this data. The main one being that this information is self-reported, and individuals may not have access to accurate health records. For example, one of the most commonly reported first symptoms is a collapsed lung (see below). It is likely that most people with a collapsed lung will have sought medical attention immediately. In the future, we plan to include clinician-reported data which will help establish the causes for the delay to diagnosis.

First Symptoms Reported

1. Fibrofolliculomas or other skin bumps (around 5 in 10 people)
2. Collapsed lung (around 4 in 10 people)
3. Kidney cancer or ‘Other’ symptom (around 1 in 10 people)

Symptoms

  • Around 8 in 10 people reported skin bumps
  • Around 7 in 10 people reported lung cysts
  • Around 5 in 10 people reported having a collapsed lung
  • Around 3 in 20 people reported having kidney cancer

This data is fairly consistent with the current literature on the proportion of people with each symptom. There are slightly more people reporting a collapsed lung and fewer people reporting kidney cancer. However, the average age of onset of kidney cancer is later than the other symptoms and so this data may change as people update the registry. This is one of the benefits of a patient registry – the ability to track how a condition affects a person over time.

Management

Skin
15 out of 62 people had treatment for their fibrofolliculomas. However, 13 out of 15 people reported recurrence of their skin bumps. Currently, there are only treatments available to remove skin bumps. There is no treatment to prevent new ones from forming.

Lung
41 out of 101 people had treatment for their lungs. The most common type of treatment was a pleurodesis (31 people), followed by a chest drain (10 people). The pleurodesis was done as a preventative measure in 11 people. Of the people who received treatment, 9 reported having a collapsed lung (in the same lung) after treatment.

Kidney
On average, people received their first kidney scan after diagnosis at age 44. This means that people were having their kidneys monitored very soon after diagnosis. Just under 9 in 10 people get regular kidney scans.

Summary

There is a huge delay between onset of symptoms and diagnosis. The reasons for this are yet to be uncovered. However, it is clear that more work needs to be done to raise awareness of BHD. Given the first symptoms commonly appear on the skin or in the lung, raising awareness of these symptoms among the general public as well as skin and lung doctors could help reduce the diagnostic delay.

More work also needs to be done to find better treatments, particularly for the skin. We are funding research to better understand fibrofolliculomas so we can identify potential therapies. In the future, we could use BIRT to help identify people to take part in clinical trials to test new treatments.

How Do I Get Involved?

We partnered with Pulse Infoframe to power the registry. Their platform is easy to use, and registration is easy.

1. Visit the BIRT website and fill out the registration form.
2. Check your email inbox and create a login to activate your account.
3. Sign the consent form.

After doing these 3 steps, you can start filling out the surveys.

We understand that there is quite a lot of information required, and it may take around an hour to complete the surveys. However, the BIRT platform is very flexible, and you do not have to do everything in one go. Your progress is tracked and is automatically saved so you can complete the surveys at your own pace. We are extremely grateful for your time and help in participating in the registry.

You can also help us by telling your family and healthcare professionals about BIRT. We have a letter you can use to tell your family members, and there is a leaflet advertising the registry to doctors.

If you have any questions or would like more information, please email us.