2022 BHD Community Symposium

We are looking forward to welcoming you to the 2022 BHD Community Symposium. The event takes place online on Saturday 8th October. Everyone is welcome including people with BHD, friends, family members, doctors and researchers.

We have a very exciting lineup this year with experts from across the world sharing their research.  We have been working with speakers to ensure the talks are pitched at a level which is accessible to everyone. There will also be plenty of opportunities to ask questions and we want you to get involved!

Join us at our research sessions and:

  • Discover more about the genetics of BHD and what we can learn from registries.  
  • Explore why certain people get certain BHD features and others do not.
  • Hear about why lung cysts may develop and how lung collapses may occur.
  • Learn about what happens in BHD kidney cancer and new treatments that are being investigated.
  • See how together we can make our voices heard and raise vital awareness of BHD.

We will also be hosting Meet the Expert sessions where you talk with BHD experts about BHD. Send your questions in advance or ask them on the day.

View our full programme to find out more about the day.

Tickets are available at: https://www.eventbrite.co.uk/e/bhd-community-symposium-tickets-327400422477

A recording will be available to all registered attendees after the event. Therefore, if you are unable to make it but are interested in any of the sessions we recommend registering.

Please contact with any questions at contact@bhdsyndrome.org

We look forward to seeing you on Saturday 8th October.

Full programme

Monitoring and Treating Inherited Kidney Cancer

Recently several papers have been published about kidney cancer that are relevant to Birt-Hogg-Dubé syndrome (BHD). In this blog, we summarise the papers and share what we can learn from them.

Is surgery or active surveillance better?

There are many different types of kidney cancer. The most common types seen in BHD are chromophobe, oncocytoma or a mixture of the two. These cancers are often slow growing, and they rarely spread. A recent paper described a case of oncocytoma and discussed whether it should be managed with active surveillance (regular scans to monitor tumour growth) or surgery.

The case described a 66-year-old man who was admitted to hospital with back pain. A CT scan showed he had tumours on both kidneys. The biggest was 3.3 cm. Due to its large size, they were concerned it may spread to other parts of the body. This is because larger tumours are more at risk of spreading.  Therefore, he had a partial nephrectomy (a type of kidney surgery) to have it removed. Samples of the tumour were then analysed, which revealed a slow-growing oncocytoma. At this point, as the cancer was shown to be an oncocytoma, the patient was given options for the smaller tumours. Either he could have them removed or have active surveillance. He opted for the surgery.

The researchers reviewing this case agreed that surgery was the best treatment option for the large tumour. However, they suggest that active surveillance may be the best option for smaller oncocytomas. This is because tumours under 3 cm are very unlikely to spread so the benefit of surgically removing them does not outweigh potential complications caused by surgery.  

Although this paper is not about BHD it does comment on a type of kidney cancer seen in BHD. It explains that oncocytomas are very unlikely to spread and that active monitoring is often the best option. This is in line with current BHD recommendations that suggest active kidney surveillance until tumours research 3 cm and then surgery.

Is active surveillance cost-effective?

The next study explored whether active surveillance of the kidneys, in conditions that predispose to kidney cancer, is cost-effective. They focused on a condition called HLRCC. Like BHD, HLRCC can cause kidney cancer. However, in HLRCC the tumours tend to grow more quickly and appear in younger people. The team assessed the cost-effectiveness of doing a yearly MRI scan in HLRCC compared with doing no MRI scans. They looked at a range of different age groups from 11 to 60. To determine if the scans were cost-effective, they assessed the effect of the scans on quality and length of life in addition to the monetary cost. They found that active surveillance was cost-effective across all age groups. Although this paper did not look at BHD, BHD does share similarities to HLRCC. Therefore, it suggests that active surveillance in people with BHD may not only positively impact their lives but be cost-effective. Before a study can be done looking at the cost-effectiveness of active surveillance in BHD, further research is needed to determine how often people with BHD should be screened.

Are there alternatives to surgery?

Lastly, we looked at a review of another type of kidney cancer called renal angiomyolipoma (rAML). rAML is a rare type of kidney cancer that is sometimes seen in BHD. Similar to the other types of cancer seen in BHD it is normally slow growing and active surveillance is recommended. Once it reaches a certain size it is then often removed by surgery.

rAML is also seen in tuberous sclerosis complex (TSC). TSC is a rare genetic condition that shares many similarities to BHD (read our recent blog post where we discuss what TSC can teach us about BHD). In addition to active surveillance, people with TSC-associated rAML can be offered a drug called an mTOR inhibitor. mTOR signalling is involved in cell growth and survival and is often overactive in cancer. mTOR inhibitors block this activity and are used to treat cancers. They are used in TSC-associated rAML to reduce the size of tumours and delay the need for surgery. Research into mTOR signalling and BHD is still ongoing so the benefit of mTOR inhibitors in BHD is unknown. However, this paper demonstrates that treatments are being developed for rare cancer types and that further research into BHD may one day find an alternative treatment to surgery.

The one stark similarity between all these papers is how there are no clear guidelines on when slow-growing kidney cancers, such as those seen in BHD, should be removed. Current research into BHD suggests it should be when they reach 3 cm. At the BHD Foundation, we want a clear answer to this question. We have launched the BHD syndrome International Registry (BIRT) to help us collect as much information about BHD as possible and drive forward research. Take part in the registry now.

Does Gender Affect When You are Diagnosed with BHD?

On average it takes 5 years for a rare disease to be diagnosed. For people with Birt-Hogg-Dubé syndrome (BHD) this means routine kidney screening often starts later than it should. The causes of delayed diagnosis have been linked to a lack of awareness of the condition. However, a recent study from Germany also suggests gender may play a role in how quickly someone is diagnosed with BHD.

Between 2005 and 2021, 158 people with BHD were recruited to this study from the Munich BHD clinic. Data was collected about their diagnostic journey and the researchers compared how this differed between men and women. To ensure that the two groups could be accurately compared there was an equal number of women and men in the study (79 of each). Additionally, the spread of ages was similar in each group and included both children and elderly people. 

Firstly, the researchers looked at what age people were diagnosed. Typically, women and men were diagnosed in their late 40’s/ early 50’s. On its own this does not tell us much as the symptoms of BHD can occur at any point. The important question is how long after the first symptom of BHD was this diagnosis made. The researchers looked at each symptom and found the following:

  • The delay between fibrofolliculomas (skin bumps) as the first symptom and diagnosis was:
    • on average 18 years for women
    • on average 16 years for men
  • The delay between a lung collapse as the first symptom and diagnosis was:
    • on average 17 years for women
    • on average 18 years for men
  • The delay between kidney cancer as the first symptom and diagnosis was:
    • on average 6 years for women
    • on average 3 years for men

Looking at this data the first thing to note is that the time between the first BHD symptom and diagnosis is large. This is particularly stark in people who had skin bumps or lung collapses. Lung collapses are often treated in hospital, so this is an opportunity to diagnose BHD. The fact that it is missed suggests that doctors may not be aware of it.

As would be expected from these results the authors also found that the first symptom of BHD was very rarely the symptom that prompted the diagnosis. 1 in 10 men were diagnosed with BHD after their first symptom. Whereas only 1 in 100 women were diagnosed with BHD after their first symptom.

 ‘The occurrence of the first typical symptoms and diagnosis of Birt-Hogg-Dubé syndrome on average is much too long, but even longer in female compared to male patients. It is therefore necessary to create more awareness both for this rare syndrome and for the possibility of gender bias.’

Professor Ortrud Steinlein, Institute of Human Genetics, LMU Munich

We spoke to the lead author Professor Ortrud Steinlein about these results and why there may be a difference between the men and women being correctly diagnosed with BHD after their first symptom.  ‘The occurrence of the first typical symptoms and diagnosis of Birt-Hogg-Dubé syndrome on average is much too long, but even longer in female compared to male patients. It is, therefore, necessary to create more awareness both for this rare syndrome and for the possibility of gender bias.’ Gender bias is seen across healthcare with women often being underdiagnosed and receiving fewer investigations than men. Professor Steinlein suggests that it may also occur in BHD.

The researchers also asked which symptom prompted a diagnosis of BHD. The answer is none of them. Instead, it was having a family history of BHD. All of the people diagnosed through family history had symptoms of BHD that had been missed. 

This study shows that many people wait years to be diagnosed with BHD and that women are less likely to be diagnosed after they develop their first symptom. This delay means people are at risk of developing more advanced kidney cancer. Most cases of BHD-associated kidney cancer are slow growing so by having regular screening it can be well monitored and treated when it reaches a certain size. This is why it’s so important to raise awareness of BHD.

Although the data paints a picture of delayed diagnosis it does cover a large time period. The researchers are hopeful things are changing. The number of people who attended the Munich BHD clinic has increased in the last 15 years from around 4 people a year to 35 people a year. Additionally, in the last five years, there has been an increasing number of people who have been diagnosed with BHD shortly after developing kidney cancer. This suggests there is an increased awareness of BHD. The authors noted that this could be due to an increased number of BHD publications in healthcare newsletters/magazines.

Although reaching a diagnosis of BHD can take years it seems that things are improving. At the BHD Foundation, we will continue to raise awareness of BHD so that people can be correctly diagnosed and receive the care they need.

Married on a Mountain with a Collapsed Lung

Joanna got married 7500ft above sea level at the top of a mountain. She didn’t realise the pain in her shoulder was her lung collapsing and that she had a rare condition called Birt-Hogg-Dubé (BHD) syndrome.

We have partnered with Rare Revolution to tell her incredible and inspirational story and raise awareness of the rare causes of pneumothorax.

You can also watch her story below:
Video Transcript

Being a doctor with BHD

Dr Bob was diagnosed with BHD after a routine scan accidentally picked up a mass on the top of his kidney. In this interview, we discuss how being a doctor affects his perspective of BHD, how we can raise awareness of BHD among doctors and the importance of being a patient advocate.

The transcript is available here.

Resources discussed in the interview.

Information resources for people with BHD

Information resources for researchers and doctors

BHD and COVID-19

Having a rare lung condition can feel scary. Having a rare lung condition during the COVID-19 pandemic adds another layer of complexity.  You may have many questions about BHD and COVID-19. In todays blog posts we summaries what the expert advises regarding BHD and COVID-19.  We also interviewed BHD patient Anna Marie Dowling about her experience getting COVID-19 with BHD.

Lung Specialist, Professor Stefan Marciniak (University of Cambridge) discussed whether COVID-19 increased the risk of lung collapses in BHD patients. He reported that in his clinic he had not seen an increase in cases and was only advising his lung collapse patients to shield if they had severe lung diseases (most of his BHD patients did not fall into this category).  He also recommended that everyone should get the COVID-19 vaccine. You can read the interview with Stefan here. He also spoke about this at a Meet the Expert event last year, which is available to watch on our webpage.

Similarly, the International Kidney Cancer Coalition provide advice on the vaccine. They are an international charity supporting people affected by kidney cancer. They advised that the benefit of the vaccine outweighs the risk and that any concerns should be discussed with a doctor. Read their statement here.

Hearing from experts is important but we also wanted the patient perspective. Anna Marie Dowling is 55 years old and lives in Ireland.  We interviewed her about her BHD diagnosis and catching and recovering from COVID-19.

What were the events that led to you seeking a genetic test for BHD?

In 2015 my then 80 year old father, who has COPD (Chronic Obstructive Pulmonary Disease), was referred for genetic testing for BHD by Professor Michael Keane, Consultant Respiratory Physician, St. Vincent’s University Hospital, Dublin as he suspected my father had the condition. My father tested positive for BHD and was provided with a letter from the Department of Clinical Genetics at Crumlin Children’s Hospital, Dublin to send to family members to inform them about the condition. On hearing of my father’s diagnosis both my sister and I immediately assumed we likely had BHD given that it is autosomal dominant and that both of us had experienced spontaneous pneumothoraces in our 40s (my sister eight times). We were keen to have this clarified and to start the monitoring process and so we sought genetic testing which confirmed what we had suspected. Thinking about our family we recalled that both my father’s lungs collapsed immediately following a quadruple (heart) bypass in his early sixties. At the time we had simply attributed this to the surgery. My father’s brother had also experienced a collapsed lung when lifting a heavy carcass when working as a butcher in his younger days. We have another sibling, my brother who chose not to be tested and so far, on the verge of 50, has had no symptoms.

What happened when you had a collapsed lung? What were your symptoms and how was it treated?

I am asthmatic and get frequent chest infections for which I am generally prescribed antibiotics and steroid tablets in addition to my regular asthma medication. In 2007 I had a bad chest infection which was not clearing. I consulted my GP several times who finally sent me to the Medical Assessment Unit at Mayo University Hospital. I had no pain but I recall walking from the hospital carpark to the hospital and coughing the whole way. At the unit I was sent for an Xray and I seemed to be waiting quite some time in the changing room after the Xray. When I was called and opened the door there was someone waiting for me with a wheelchair. I got the fright of my life. I asked if they had found something and the man said yes but said that it was something that could be rectified. My experience of having the drain inserted was a difficult one. I found it quite traumatic. The first two insertions in two different locations were unsuccessful necessitating a third attempt, this time by the surgical team, which succeeded.  I was terrified to sleep that night while I had the drain in case it fell out and had to be reinserted. Following a few days in hospital and removal of the drain I was discharged home. It took me quite some time to fully recover as I was very tired following the experience and, possibly due to poor breath control, developed problems with talking due to hoarseness. I was diagnosed with vocal chord nodules and had to undergo sessions of speech and language therapy. I was off work for two months in total.

Since you’ve been diagnosed with BHD how have you managed the condition?

Since diagnosis I have followed the monitoring guidelines. I get regular MRI kidney scans and consultations with the renal consultant. So far all my renal scans have been clear thankfully, though my sister who is 13 months youngers has some small kidney cysts. I have regular check-ups with my respiratory consultant also and as there is a family history of colon cancer (my father, his sister and his mother) I have regular colonoscopies. I don’t seem to have any skin lesions. I think I probably had a consultation with a dermatologist early on but can’t fully recall now. For the first few years after my collapsed lung I was terrified every time I got a chest infection that I would get another collapsed lung. That fear has subsided considerably now but I never delay getting treatment when I get a chest infection.

How did the COVID-19 pandemic change this?

I was advised to cocoon/shield at the start of COVID-19. I am a health care professional but fortunately, due to the nature of my work, I have been able to work from home. My Occupational Health department have recommended this and my manager and colleagues have been very supportive (*Note from the BHD Foundation: Shielding is not recommended specifically for BHD patients, however each individual case is different and your doctor will be able to advise further if you have any questions). It has been isolating as I live alone but I have felt safe because of this. COVID-19 has been frightening due to the uncertainty of how it could affect me. I was delighted to get the vaccines and am currently triple vaccinated.

“COVID-19 has been frightening due to the uncertainty of how it could affect me. I was delighted to get the vaccines and am currently triple vaccinated.”

What were your concerns about getting COVID-19 with BHD Syndrome?

My main concern about getting COVID-19 with BHD was how it would affect my chest and would it cause a collapsed lung. I understand that COVID-19 affects the same part of the lung as where the BHD cysts are usually located. (*Note from the BHD Foundation: COVID-19 can affect the whole lung. BHD cysts are normally found at the base of the lungs).  I also was fearful that if I needed ventilation that that would be problematic due to BHD as there would be an increased risk of pneumothorax with ventilation and that might affect my chances of recovery (*Note BHD Foundation: Read more about lung collapses and COVID-19 here). I thus kept my contacts to an absolute minimum and apart from my father and my partner, only met one or two people outdoors and wearing a mask.

What happened when you got COVID-19 and how was the recovery process?

Despite barely meeting anyone in two years I somehow contracted COVID-19 after Christmas this year. I had no contact with anyone who tested positive so have no idea how I caught it. I live alone so isolating was not a problem. I tested positive on an antigen test the day prior to developing symptoms. As soon as I developed symptoms I contacted the out of hours doctor and asked for a prescription for steroids as COVID-19 went straight to my lungs (*Note from the BHD Foundation: Steroids are not a standard treatment for people (including BHD patients) who develop COVID-19. It depends on severity of COVID-19 symptoms and medical history. Discuss with your doctor if you have any concerns). These definitely helped, though as they are immunosuppressive, there is caution in prescribing these with COVID-19. I have a nebuliser at home because of my asthma and I used that when I was struggling with coughing. I also monitored my pulse rate and oxygen saturation regularly. While I had a headache one or two days and gastric symptoms one day, my respiratory symptoms were the main issue. It was a little frightening not knowing how the COVID-19 would progress as I was aware that things can take a turn for the worse in the second week. The second week was certainly more difficult for me in that I was more fatigued and had muscle weakness. However, unlike when I have a regular chest infection and am awake coughing during the night, I managed to sleep well each night with COVID-19 which was a relief. I also got up, showered and dressed each day as I felt it was better to be up and moving around than lying in bed. I was back working from home after two weeks though I was tired and also developed an earache which lasted for a further week. I am fully recovered now thankfully.

“Unlike when I have a regular chest infection and am awake coughing during the night, I managed to sleep well each night with COVID-19”

What advice would you give to someone who has been newly diagnosed with BHD?

I would say not to panic. I believe knowledge is power. Everyone has something or will develop some health problem at some stage and knowing what we are susceptible to developing means that we have an advantage as we can be monitored and catch things early if they develop. I would say don’t delay seeking help if you have suspicions that you are developing a collapsed lung as the treatment can be less intrusive if the collapse is partial as opposed to complete. I would also say not to get caught up in fear about it and live your life and enjoy it. I understand BHD is not a life-limiting condition which is good to know. Also, inform people about the condition as not many people know about it. My respiratory consultant had not heard of BHD before I told him about it but I found out at a later appointment that he had subsequently diagnosed people with it. Also, it’s important to let your family members know about it in case they may have it.

How can the BHD Foundation support the BHD Community?

It is great to have an organisation in relation to our condition. I think educating the public and doctors about BHD is important as, given the inheritance mechanism, there must be many people out there who have BHD but are not aware of it. The more people know about it the greater likelihood that those with BHD will get the correct diagnosis and there will be a better chance of more research into the condition.

We greatly appreciate Anna Marie sharing her experience of having COVID-19 with BHD. 

If you have any questions about BHD and COVID-19, please contact us at contact@BHDFoundation.org

New BHD Awareness Leaflet for Doctors

It takes on average 4 years for a rare disease patient to reach a diagnosis and the BHD community is no different. Nearly every person we talk to describes the challenges of being diagnosed with BHD and how many doctors have never heard of it.

To raise awareness of BHD among doctors we have created a leaflet dedicated to the symptoms of BHD. We hope that this resource will prompt doctors to consider BHD when investigating patients with collapsed lungs, lung cysts, skin bumps and kidney cancer. The leaflet also signposts to genetic test centres so that doctors have the information to correctly refer their patients.

We will be distributing the leaflet at key conferences and events, and you can help too by sharing it with your doctors.  

View the leaflet PDF. The printable version can be found here.

Day of Giving

Today is the Day of Giving, a day when people come together to support a cause or community. We are developing a BHD patient registry which is a centralised database that collects information about people with BHD. They are particularly useful in the context of rare diseases as they help researchers and clinicians to build a more complete picture of the condition.

View our infographic to find out more. The infographic includes information about our September meeting which has now taken place however there are still ways you can get involved and support the development of the registry.  

Ways to help:

1. Select Myrovlytis Trust on Amazon Smile. We have joined forces with Amazon Smile. Select Myrovlytis Trust as your charity and for each purchase, you make through Amazon Smile, Amazon will donate 0.5% to us.

2. Make a donation through PayPal. Select your charity as the Myrovlytis Trust or use our charity number 1122073 and donate.

3. Sign up for our newsletter to keep up to date with the progress of the registry and associated volunteering opportunities.

4. Share a fundraising idea with us and we can work together to make it a reality. Email us at contact@bhdsyndrome.org

5. Share your time and expertise. Do you have a skill in design, translation or other? We would love to know and will get in contact with volunteering opportunities that match your skill. Email us at contact@bhdsyndrome.org

6. Share our Twitter and Facebook posts with #GivingTuesday

We want to send out a massive thank you to the BHD community for all your support since the relaunch of BHD Foundation this year.

Lenke’s BHD Story: Pregnancy

Lenke was diagnosed with BHD after a collapsed lung during her pregnancy. In this interview, she discusses her pregnancy, genetic testing, her decision not to have IVF and her yearly BHD dates with her mum at the clinic.

You can watch the interview below.

A transcript of the interview is available here. You can read the transcript in Dutch here.

Why does BHD cause lung cysts?

Birt-Hogg-Dubé syndrome is caused by a mutation in the gene folliculin (FLCN). Unravelling the functions of FLCN has been a focus of research into BHD, because if we can determine how FLCN mutations cause the characteristics of BHD we can potentially reverse them or even prevent them from happening. Lung cysts are a common feature of BHD with cysts being present in up to 80% of patients. An exciting study by Ikue Tai-Nagara and colleagues discovered a new function of folliculin and hypothesised that when lost it may result in lung cyst formation (1).

The body contains different systems, working in harmony to keep us functioning including the cardiovascular and lymphatic systems. The cardiovascular system transports blood throughout the body whereas the lymphatic system collects excess fluid, clears waste, and transports immune cells. The vessels of these two systems are very similar and both are lined with a layer of cells known as endothelial cells. However, throughout the body, the lymphatic and blood vessels are mostly separated. Imagine they are two different train tracks, structurally similar but carrying different cargo.

The research team investigated what would happen if FLCN was knocked out (removed) in endothelial cells. They studied mouse models at different developmental stages and found that knocking out FLCN in mice that were still developing resulted in enlarged and blood-filled lymphatic vessels. Examining both the lymphatic vessels and blood vessels under a microscope they observed that the lymphatic vessels were developing offshoots towards veins (the blood vessels that transport blood from the organs to the heart) and the veins were developing offshoots towards the lymphatic vessels. It appeared that there was an attraction between the two systems that had not previously been present. Additionally, the lymphatic endothelial cells were dividing rapidly which was the likely cause for the enlargement of the lymphatic vessels.

Next, the researchers investigated why knocking out FLCN caused a change in the relationship between the lymphatic vessels and veins and one key gene stood out. PROX1 controls the development of lymphatic endothelial cells. In mice where FLCN was knocked out not only was PROX1 expressed in the lymphatic endothelial cells (where it should be) but it was also inappropriately expressed in the endothelial cells of the veins. The significance of this expression was highlighted when PROX1 was deleted from the endothelial cells and the characteristics of the vessels normalised.

Next, they needed to connect how knocking out FLCN caused PROX1 expression to increase. They focused on TFE3, which is well documented as being regulated by FLCN (find out more in our recent blog post). Firstly they found that TFE3 was highly expressed in the endothelial cells of the FLCN knockout mice. They then looked at human endothelial cells and found that knocking down FLCN increased PROX1 and that this could be reversed by also knocking down TFE3. They also showed that TFE3 bound and regulated the PROX1 gene. Therefore, when FLCN was knocked down and could no longer regulate TFE3, PROX1 increased resulting in changes to the lymphatic vessels and veins.

So, what has all this got to do with the lungs? The final experiment involved looking at lung samples from three BHD patients. The samples were compared with normal lung specimens and non-BHD cyst-filled lungs. Significantly, only the BHD lung specimens showed evidence of lymphatic vessels filled with blood, inappropriate PROX1 expression and increased TFE3 expression. This suggests that the structural changes in the lungs such as cysts could be linked with the disruption of the lymphatic and cardiovascular systems.

Altogether this research demonstrates a new role of folliculin as a gatekeeper of the lymphatic and cardiovascular system. New research is on the horizon looking further into how lung cysts form and how these pathways can be targeted therapeutically to improve the lung symptoms associated with BHD.


1.      Tai-Nagara I, Hasumi Y, Kusumoto D, Hasumi H, Okabe K, Ando T, et al. Blood and lymphatic systems are segregated by the FLCN tumor suppressor. Nat Commun [Internet]. 2020 Dec 1 [cited 2021 Oct 27];11(1). Available from: /pmc/articles/PMC7725783/