BHD Toolkit: Explaining the Different Types of Healthcare Professionals

Birt-Hogg-Dubé Syndrome (BHD) can be a complicated condition as it has a wide variety of symptoms. This means you may have to see several different types of doctors during your BHD journey. We understand this may be a confusing and overwhelming process, especially when you’ve just been diagnosed with BHD and don’t know where to start. In this toolkit, we break down the different types of healthcare professionals you may come across and when you would see them.

It is important to remember you might not need to see all the different types of healthcare professionals in this list. Who you see will depend on the symptoms you have and your healthcare system. We have tried to make this list as inclusive as possible. Please let us know if we have missed anyone off the list, or if there is another name for the type of doctor in your country. Get in touch with us by email.

Diagnosis

Clinical Geneticist

This type of doctor specialises in the diagnosis and management or treatment of genetic conditions. You may see a clinical geneticist as part of your BHD diagnosis. This may happen before your genetic test or afterward to discuss management of BHD. You may also see a clinical geneticist if a family member has been recently diagnosed with BHD and you are seeking testing. They may also refer you to have scans of your lungs or kidneys. For more information on what happens during a clinical genetics appointment, read our previous toolkit here.

Other names: Medical Geneticist

Genetic Counsellor

A genetic counsellor provides information to individuals and their families about genetic conditions. This can range from information about genetic testing through to family planning and beyond. The Macmillan Cancer Support website has a great page on what to expect during a genetic counselling appointment. Read it here.

Family Doctor

Also known as a primary care doctor or GP (general practitioner) this is often the first person you see for many medical issues. You may see this type of doctor during diagnosis of BHD as they can often refer you to the correct doctor for further testing. As BHD is so rare, they may not have heard of the condition before. It might be useful to take our information leaflet with you to give to your doctor if you think you have BHD. Find our leaflets here. Even if they haven’t heard of BHD, they will still be able to refer you to the correct person based on your symptoms.

Emergency Doctors

One of the major routes for BHD diagnosis is through having a collapsed lung. If you have a collapsed lung, you might end up in the emergency department of your nearest hospital. If you haven’t been diagnosed with BHD but you or a family member have had repeated collapsed lungs (or any other BHD symptoms) it is important to tell your emergency doctors. This may aid the diagnosis of BHD.

Skin

Dermatologist

A dermatologist is specifically trained to diagnose and treat skin conditions. For diagnosis, they may take a biopsy (a small sample) of your fibrofolliculoma and send it to a lab for further testing (see pathologist below). BHD is also associated with other types of skin lesion. Find out more about them here. They are also qualified to perform several techniques to remove the lesions you have. These treatments are usually only temporary as they do not prevent the growth of new lesions. Find an overview of treatment options here.

Lung

Pulmonologist

A pulmonologist specialises in conditions affecting the lungs. They can help manage any lung symptoms of BHD you have.

Other names: Respirologist, Pneumologist

Thoracic Surgeon

If you have been referred for surgical treatment for your lungs, you will see a thoracic surgeon. These are surgeons who specialise in the chest area. Find out more about the different types of lung treatments here.

Kidney

Urologist

A urologist is a doctor who specialises in treating conditions affecting the urinary system, including the kidneys. It is recommended that you get regular kidney scans to identify and treat any kidney cancer as quickly as possible. Urologists are also surgically qualified. If you have kidney cancer and need to have surgery to remove any tumours, a urologist will normally carry out this procedure.

Nephrologist

Unlike a urologist, this type of doctor only treats conditions relating to the kidney and are not surgically trained. You may see a nephrologist instead of a urologist for management of your kidneys.

Oncologist

If you have kidney cancer, you may be referred to an oncologist. Oncologists are highly trained in treating cancer. If you need other treatment for cancer, aside from surgery, they can recommend a treatment plan.

Other

Radiologist

A radiologist is a doctor trained to analyse imaging scans. They will write a report of their findings and send this to the relevant doctor to give you the results. You will not normally see a radiologist.

Radiographer

A radiographer is the person who carries out the scan. They will be who you see when you get a scan of your lung or kidneys and will take you through the process.

Pathologist

A pathologist is a doctor who will examine biopsies and can help in the diagnosis of BHD. They will be able to confirm if a skin lesion is a fibrofolliculoma. They can also diagnose which type of kidney cancer a person has. This can help guide the treatment and management of BHD. You will not normally see a pathologist

Anaesthetist

Anaesthesia is given to an individual for surgery and other medical procedures so they can be carried out safely and without pain. An anaesthetist is trained to provide anaesthesia in these situations. They will monitor you throughout the surgery.

BHD Foundation Patient Advisory Board Meeting Report

The first BHD Foundation Patient Advisory Board (PAB) meeting was held on Tuesday 3rd May 2022. The aim of this was to discuss the needs of the community and future directions for the Myrovlytis Trust and BHD Foundation. This report highlights the major topics of discussion and outcomes.

1. Awareness

Raising awareness of BHD is a core value of the BHD Foundation and is also extremely important to the PAB. As an international charity, we are thrilled that our PAB is made up of people from the UK, mainland Europe and the US. This enables us to gain insights into different healthcare systems so we can increase our platform for awareness. We discussed the different types of doctors we should be targeting and strategies to reach out to them.

We have recently created a leaflet aimed at raising awareness of BHD among healthcare professionals. We are in the process of sending this leaflet to different doctors and identifying the best approaches to use. One of these approaches is to distribute the leaflet at relevant professional conferences. It may even be possible to attend the conference to give a presentation or a poster about BHD. The PAB suggested we could contact national professional organisations for different types of doctors and include our leaflet or information about BHD in their newsletters. We thought this was a great idea and are creating a list of relevant organisations to contact.

Members of the PAB also mentioned that whenever they go to a hospital appointment, they take information with them about BHD. They give this information to their doctors to help raise awareness of the condition. We have created several BHD information leaflets that can be used for this purpose. If possible, we would encourage you to do the same thing. The more people we have raising awareness of BHD, the more people we will reach. Find our information leaflets here.

2. Resources

The biggest resource we have is the BHD Foundation website. Last year, we updated the content of the website to ensure the information was as up to date as possible. Now, we want to make the content as accessible and visually stimulating as possible, using a more modern website design. We are looking forward to starting work on this project with support and input from the PAB.

We were also keen to identify topics that the BHD community would like more information or guidance on. The PAB discussed the uncertainty many people with BHD have about the risks of flying. We agree this is a common concern and will be looking into developing a resource to answer this, and other lifestyle questions, about BHD.

Another topic of discussion at the meeting was regarding health insurance and BHD. As an international charity, this is difficult as every country has a different healthcare system. However, we realise a large proportion of our community are based in the US and so we will be seeking advice on the best way to discuss this topic. Over time we aim to expand our information to cover different healthcare systems.

3. Events

We have recently announced our BHD Symposium this year will be aimed at the BHD community. The event will be held online on Saturday 8th October, 3 pm – 8 pm UK time (10 am – 3 pm EST). Tickets are free and available now by registering here. We are thrilled to have members of the PAB involved in organising this event. We asked the PAB if there was a particular topic about BHD they would like to be featured. As BHD has such a range of symptoms, it wasn’t surprising that everyone had different thoughts! We will take this into consideration and look forward to creating a diverse programme of events.

4. Research
Through the Myrovlytis Trust (who manage the BHD Foundation), we have funded over £7 million into BHD research over the past 15 years. We are committed to funding BHD research until there are new treatments or even a cure for the condition. One of our main missions is to unite researchers, clinicians and people with BHD. It is important to us that the research we fund is in the best interest of the BHD community. We are delighted that our next round of funding will give our PAB the chance to review grant applications.

We are also extremely pleased to have recently launched the BHD Syndrome International Registry (BIRT). We believe that the registry is an important step towards finding new treatments or a cure for BHD. It is also a chance for the community to contribute to research so we can find out more about the condition. One of our major goals is the creation of standardised diagnostic and management guidelines. These will improve the quality of life of people with BHD through early diagnosis and improved management of their condition. Find out more and sign up to the registry here.

We would like to thank the PAB members for their time and thoughtful input at this meeting. The BHD Foundation and Myrovlytis Trust work to raise awareness and fund research to improve the quality of life of those with BHD. We are delighted to have established the PAB to ensure that the voices of people with BHD are being heard. We are proud to be able to amplify these voices and are committed to advocating for the community to empower people with BHD.

DNA Damage, Folliculin and Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare type of cancer found in the lining of the lungs. 9 out of 10 cases of MPM are caused by exposure to asbestos. Now banned in most countries, asbestos is a fibrous material that was widely used in the building industry. Inhaling asbestos fibres can damage the lining of the lungs and, over time, lead to cancer. 2 studies have presented data on genetic risk factors associated with MPM. Understanding the risk factors for this cancer may help direct screening and treatment guidelines.

You might be wondering why the BHD Foundation are blogging about MPM. These studies caught our attention due to the mention of folliculin (FLCN). Mutations in FLCN cause Birt-Hogg-Dubé Syndrome (BHD).

The first paper studied the association of kidney cancer with MPM. They looked at the records of 8295 people with kidney cancer. 6 people had kidney cancer and MPM. 2 of these were found to have genetic mutations. One mutation was in a gene called BAP1. This has a known link to MPM. The other individual had a mutation in FLCN. One limitation of this study was that it was primarily designed to look for mutations in BAP1 and not FLCN. So it is possible that other individuals had mutations in FLCN but were not identified.

The authors of the second paper performed genetic sequencing on 113 patients with MPM. Mutations in 9 different genes, including FLCN, were found. Many of these genes are involved in a pathway in our cells called the DNA damage response. The DNA damage response is one of the ways our cells can repair our DNA if it gets damaged. DNA can be damaged by external sources such as smoking, UV exposure and asbestos. When our DNA is damaged, there is an increased risk of cancer. If there is a mutation in one of these DNA damage repair genes, the pathway doesn’t work, and our DNA cannot be repaired. It has been shown previously that FLCN also plays a role in the DNA damage response.

Everyone has 2 copies of FLCN and only one of them needs to be mutated to have BHD. The authors also observed loss of heterozygosity for FLCN. This means that a mutation in the second copy of FLCN was also found. In BHD, mutation in the second copy of FLCN is thought to be required for the development of kidney cancer.

The authors also looked at asbestos exposure. Patients with MPM had been exposed to more asbestos throughout their life. A mutation in any one of the genes identified in this study was associated with MPM development and a lower exposure to asbestos. This highlights the important link between genetics and the environment in cancer.

Taken together, these studies have found 2 cases of individuals with BHD and MPM. Neither study reported the level of asbestos exposure in these individuals. Asbestos is likely still the primary driver of MPM and, to the best of our knowledge, these studies represent the only cases of BHD and MPM. This means that BHD is unlikely to increase the chance of developing MPM.

MPM is usually diagnosed at a later stage of the disease and as such  outcomes are poor. Increasing our knowledge of the risk factors of MPM can guide screening and diagnose MPM earlier. Understanding the genetic contribution to MPM can also help direct the treatment of the disease. Cancer treatment can vary depending on many factors including genetics. In the future, there may be drugs available that will be particularly effective in individuals with mutations in genes involved in the DNA damage response.

If you would like to know more about MPM please visit the Mesothelioma UK website.

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

Spring BHD Case Report Round-Up

Our spring case report round-up features 3 papers identifying unusual cases of BHD. The first 2 report cases of BHD alongside other genetic mutations. The last paper documents the first account of 2 different mutations in folliculin (FLCN) in the same individual.

Case Report 1

A 55-year-old male had reported shortness of breath, chest tightness and a cough. In the past 2 years, he had been to hospital 4 times for a collapsed lung (pneumothorax). A CT scan of his lungs showed numerous lung cysts and his right lung was collapsed. He had no kidney tumours or skin lesions, and all other tests were normal. However, his fingers on both hands had visible differences and were not fully extended. The patient’s son also had similar fingers and a history of collapsed lungs. Genetic testing revealed that both the patient and their son had mutations in FLCN and another gene called FBN2. The diagnosis of these individuals was BHD and congenital contractural arachnodactyly (CCA). CCA is a rare inherited connective tissue disorder and was the cause of the hand symptoms. It can sometimes be confused with another disorder called Marfan syndrome. Marfan syndrome can also cause collapsed lungs. This report highlights the importance of genetic testing and getting the right diagnosis. The correct management strategies for BHD, including regular kidney scans, can now be put in place to minimise the risk of kidney cancer.

Case Report 2

A 56-year-old woman was referred to the cancer genetics counselling service due to her history of multiple cancers. She had 2 melanomas (skin cancers), thyroid, parathyroid and kidney cancers. She had also been to hospital 4 times for a collapsed lung. She had no skin lesions and no family history of collapsed lungs or kidney cancer. Genetic testing confirmed the diagnosis of BHD. As well as a mutation in FLCN, a mutation in the gene BRCA2 was also discovered. Mutations in BRCA2 increase the risk of breast and ovarian cancer. After diagnosis she developed further kidney cancers which spread to her liver. In BHD, kidney cancer is normally slow growing and does not spread. She was also diagnosed with breast cancer. This case report highlights the importance of genetic screening and early diagnosis. Knowledge of these mutations allows the individual to get regular screens to check for any cancer. It also allows their family members to be tested and, if necessary, get screened as well.

Case Report 3

This case report featured 3 individuals who were diagnosed with BHD through referral to the dermatology (skin) clinic. The first patient had multiple small, skin-coloured, dome-shaped papules on her face and neck and a family history of colon cancer. A biopsy of the skin lesions was taken, and they were confirmed to be angiofibromas. CT scans showed she had cysts in her lung and kidneys. Genetic testing showed she had 2 different mutations in FLCN, and she was diagnosed with BHD.

To our knowledge, this is the first time 2 different FLCN mutations have been reported in the same individual. We have 2 copies of every gene. A mutation in one copy of FLCN is enough to cause the symptoms seen in BHD.  This patient’s parents are no longer alive, and so it is impossible to tell whether just one or both copies of FLCN are mutated.

The third case described two further patients, a mother and daughter. The mother, a 76-year-old, had widespread skin lesions on her face and previously had colon cancer. The skin lesions were confirmed to be trichodiscomas and genetic testing revealed a mutation in FLCN. Her daughter also had trichodiscomas and a history of collapsed lungs and parotid oncocytoma. She was also diagnosed with BHD after genetic testing showed she had inherited a mutated FLCN gene from her mother.

These case reports all document ‘firsts’ for BHD and expand our knowledge of the condition. Each case is different, yet they all highlight the importance of genetic testing. Genetic testing helps diagnose conditions. Early diagnosis of BHD is important to ensure any kidney cancer is found and treated quickly. Genetic testing ensures the correct diagnosis is made. As shown here, it can also identify other mutations or conditions that might have been missed. We have more information on genetic testing here. You can read our toolkit blog post discussing what to expect when going to a clinical genetics appointment here.

Do BHD Lung Cysts Correlate with Collapsed Lungs?

A recent study has been published characterising lung cysts in a small group of Birt-Hogg-Dubé Syndrome (BHD) patients in China. The study examined the features of lung cysts to see if there was any relationship with having a collapsed lung (pneumothorax).

A total of 26 BHD patients from 11 families aged between 20 and 68 years were selected for the study. Just over half (14 out of 26 individuals) had experienced a collapsed lung. Nearly half of those (6 out of 14 individuals) had experienced a lung collapse between 2 and 4 times. None of the patients had any skin or kidney symptoms typical of BHD.

A lung CT scan was available for 23 of the individuals. In total, 2323 lung cysts were documented across the scans. The lung cysts ranged from 4 – 110 mm in diameter. The authors found a significant difference in some features of lung cysts between people who had a collapsed lung and those that didn’t. The size and volume of the largest cysts were bigger in people who had a collapsed lung. However, there was no difference in the number of cysts between the 2 groups.

One measurement, called the short-axis diameter, can often reflect the tension of the cyst. Imagine there are 2 cysts that have the same volume but differ in size so that one is long and thin and one is more round. The one that is more round has a bigger short-axis diameter and a higher tension and is more likely to burst.

There were some limitations of the study. Firstly, the sample size was small and secondly some individuals had a history of pneumothorax. This may have affected the characteristics of the lung cysts observed in this study. In the future, they would like to study more BHD patients to better observe the relationship of lung cysts and collapsed lungs.

The authors also spoke about the need for awareness of BHD among clinicians. They particularly mentioned emergency department doctors and surgeons. Individuals who experience a collapsed lung often go to emergency departments for treatment. Although the collapsed lung needs to be treated quickly, time should also be taken to investigate any underlying causes. Around 1 in 3 individuals with BHD get kidney cancer. Early diagnosis of BHD is important to recognize and treat any kidney cancer. The BHD Foundation works to raise awareness of BHD among clinicians. We have recently developed a leaflet dedicated to the symptoms of BHD that will prompt doctors to consider a BHD diagnosis.

BHD Syndrome International Registry – User Guide

We are delighted to announce the launch of the BHD Syndrome International Registry (BIRT). We want to collect as much information as possible about BHD so it is really important than as many people join the study as possible. You can find out more about the registry and it’s aims here. To help with the process, our partners Pulse Infoframe have created this step-by-step guide to registering and completing the surveys.

You can download the guide here as a pdf or as a word document.

If you wish to read the guide in a different language, please select your language by clicking ‘Other Languages’ at the top right of the screen and download the guide as a word document. We will also be launching the registry in French, German and Spanish in the coming months, and hope to expand to other languages in the future!

If you encounter any technical problems registering or completing the survey please email us with details of the problem and include the device and browser you have had the issue on and any screenshots of the problem if they are helpful.

We will also be holding drop-in zoom sessions over the next few weeks. If you are having trouble registering or have any questions about the registry, please drop in on zoom. Our zoom sessions are taking place at the following times:

  • Tuesday 12th April 2 – 3 pm UK time (9 – 10 am EST)
  • Saturday 23rd April 5 – 6 pm UK time (12 – 1 pm EST)

The link to join the zoom session will be circulated through our mailing list. To register for updates, please sign up here.

If you can’t make any of these times, please get in contact with us by email and we can arrange a time convenient for you.

The BHD Syndrome International Registry is now Live!

Guest Blog Post by Pulse Infoframe.

The Myrovlytis Trust, BHD Foundation, and Pulse Infoframe are pleased to announce that the BHD Syndrome International Registry is open for recruitment.

What Is Birt-Hogg-Dubé Syndrome?

Birt-Hogg-Dubé (BHD) syndrome is a rare, inherited condition that is characterized by the development of benign skin tumors (fibrofolliculomas), pulmonary cysts, collapsed lung (pneumothorax), and a predisposition to kidney (renal) cancers. It’s an autosomal dominant disorder caused by a mutation in a gene called folliculin.

There is no cure for BHD, so patients must have individual symptoms treated as they appear.

How Many Patients With Birt-Hogg-Dubé Syndrome Will Develop Renal Cancer?

BHD Syndrome causes renal cancer in about 30% of patients. The kidney cancer is slow growing and rarely metastasizes. However, once tumors become greater than 3 cm in diameter, patients need surgery to remove them.

How Rare Is Birt-Hogg-Dubé Syndrome?

Currently, around 600 families are known to be affected by Birt-Hogg-Dubé Syndrome; however it is believed to be far more prevalent, and the condition is likely underdiagnosed. This is in part why the Myrovlytis Trust and BHD Foundation have begun the BHD Syndrome International Registry, BIRT for short. Not only will it give a better understanding of the prevalence of the condition, it will aid vital research that will lead to new treatments or hopefully even a cure for BHD.

What Is the BHD Syndrome International Registry (BIRT)?

BIRT is a patient registry for Birt-Hogg-Dubé Syndrome. It will help healthcare practitioners and researchers better understand the characterization of the disease, its prevalence, and the disease trajectory. Another goal is to use the data to help improve the quality of life for the BHD community, to reach consensus on the diagnosis and management of BHD, and, ultimately, to help researchers develop treatments or a cure. The Myrovlytis Trust and BHD Foundation are managing the patient registry, and Pulse Infoframe is developing and hosting it.

How Will BIRT Help Birt-Hogg-Dubé Patients?

By participating in BIRT, BHD patients will not only learn about BHD over time, but they’ll also contribute to a growing body of knowledge about the syndrome. This knowledge will be used to develop new therapies.

Broadly, the BHD Syndrome International Registry aims to achieve the following goals:

  • Develop clear guidelines for diagnosis and management.
  • Determine the prevalence of BHD.
  • Determine if there are other manifestations associated with BHD (aside from those already known in the skin, lungs, and kidneys).
  • Collect information on the type of kidney cancer most likely to develop in BHD.
  • Collect information on how patients manage their symptoms on an ongoing basis.
  • Determine if particular genetic variants are associated with particular manifestations.
  • Collect lifestyle information to understand if environmental factors influence the treatment or management of Birt-Hogg-Dubé Syndrome.
  • Assess the quality of life of those living with BHD.
  • Use the registry as a database to recruit for clinical trials.

How Does BIRT Work?

In a nutshell, participants enter data about themselves into BIRT to make the data available for research. The more participants who contribute to the registry, the more data can be collected to aid research.

The BHD Syndrome International Registry goes much further than this. Participants can view and update their information in a user-friendly environment that includes patient reported outcomes instruments, previously uploaded clinical results, and other educational and engagement tools. This means they’ll not only add their own information to the patient registry, but, in time, they’ll also have one place for all their clinical information, and they’ll learn more about BHD.

An Important Part of Research: Patient-Reported Outcomes

Patient-reported outcome (PRO) surveys provide the context necessary for researchers and drug developers to understand patient experience. PRO surveys are a part of BIRT and have been designed by QualityMetric, a partner of Pulse Infoframe.

BIRT includes QualityMetric’s SF-36v2 PRO survey, which is standardized with regulatory-ready data for a greater understanding of disease impact for patients across disease conditions. This eliminates the obstacle of poorly understood or undocumented symptoms when measuring quality of life as it relates to the health of participants. By integrating the SF-36v2 PRO survey, researchers who study the data in BIRT may better understand what participants experience. Furthermore, the survey provides continuity in measuring how BHD Syndrome affects the daily lives and the mental health of those with this rare disease. This can lead to a better understanding of BHD Syndrome, as well as an increased awareness of potential therapy initiatives.

What about Patient Privacy?

Patient privacy and data security are extremely important to everyone involved in BIRT. The Pulse Infoframe platform was designed from the ground up to support international regulatory data standards such as GDPR, HIPAA, PHIPA, etc. Patient privacy therefore begins with removing all identifying information, such as name, age, sex, and more from a patient’s health information as it’s entered into BIRT.

Next, let’s discuss researcher and clinician access. Security processes and technologies are integrated into all aspects of the BHD patient registry, so only the right people may access the data they are authorized and entitled to see. This access also includes what patients consent to sharing: no data are shared without a patient’s clear consent. A consent form is digitally available and verified by DocuSign.

Finally, there’s what patients themselves can access. Patients can access to their own data at any time and can consent to share their data with providers and other relevant parties as they see fit.

How to Learn More and Register

The Myrovlytis Trust has funded over £6 million in research conducted in over 20 academic institutions in eight countries for BHD since its founding in 2007. The BHD Syndrome International Registry will make it easier to continue researching Birt-Hogg-Dubé Syndrome almost anywhere in the world.

To learn more about the BHD Syndrome International Registry, visit the BHD Foundation Registry page. For patients who are ready to register, they can visit BIRT directly here.

A rare occurrence of BHD and PEComa – perspectives from a patient and a doctor

CF discovered they had BHD after a lung CT scan following a diagnosis of a rare type of sarcoma called epithelioid PEComa (perivascular epithelioid cell tumour). Read their story and their inspiring, positive approach to life after BHD diagnosis. Since PEComas are so rare, we also interviewed Dr Andrew Wagner, a world leading expert in the field for more information on the crossover between BHD and PEComas.

Interview with CF, USA

When were you first diagnosed with BHD? 
March 2020

How did you get diagnosed and what was the process?
In January of 2022, with the help of the BHD Foundation and one other PEComa patient, I learned that there is a link between my PEComa and BHD diagnoses. In an effort to learn more, in February my husband and I met with Dr. Andrew Wagner (not to be confused with my oncologist mentioned earlier), the world’s leading expert in PEComas at Dana Farber in Boston. Dr. Andrew Wagner is interested in researching the link between PEComas and BHD. At this time, there are only four of us (three living) with these two diagnoses. His team will be genetically sequencing my PEComa. We are hopeful that having the FLCN mutation will help with PEComa and mTOR pathway research (See Dr Wagner’s comments below). By the way, Dr. Andrew Wagner does not think that my FLCN mutation puts me at higher risk of creating more PEComas, nor does he think that other people with BHD should worry about an occurrence of this very rare type of sarcoma.

What impact has your BHD diagnosis had on you and your family members? 
Gratefully, none. My diagnosis led to my mother also getting a formal diagnosis. She had a CT scan confirming lung cysts and an abdominal MRI, which showed two small renal cysts that her doctor is monitoring. My only sibling also has fibrofolliculomas but has chosen not to be tested for BHD at this time. I am grateful that we now know about our underlying condition.

What are your symptoms of BHD and how do you manage them? 
I have no symptoms aside from my lung cysts. I have been a runner most of my life, including running several half marathons, and have never felt any effects from the cysts. I practice yoga every day, and have never noticed problems breathing in any poses. I don’t avoid airline flights and have taken many flights with the lung cysts including long international flights, without any problems. I am aware of the risks of pneumothorax, so I am careful not to overdo my activity in the 24 hours after being on an airplane. I am self-conscious about my fibrofolliculomas which began showing up in my late twenties. I have them across the bridge of my nose, a sprinkling of them on my neck, upper chest and ears. I have discussed treatment options with my dermatologist but I understand that there are not any permanent solutions. My friends and family tell me that my fibrofolliculomas are not very noticeable.

What treatments/monitoring have you had/are having? 
For my PEComa diagnosis, I have an annual lung CT scan and a pelvic MRI. For the BHD diagnosis and monitoring my kidneys, an abdominal MRI has been added to my scan order. Gratefully, my scans have all remained clear. I also get a thyroid ultrasound once a year due to the possibility that BHD might play a role in thyroid carcinomas (*Note from BHD Foundation: currently there is not enough evidence to conclusively say there is a link between BHD and thyroid cancers, see here for more information).  In December 2021, I met with an interstitial lung specialist to learn more about my lung cysts. He informed me that although a spontaneous pneumothorax is possible, it would be unlikely to be fatal. He said that I should just live my life without worrying about the blebs, with the two exceptions of not riding in non-pressurized aircraft and avoiding scuba diving. Those restrictions pose no problems for me.

What advice would you give to someone who has been newly diagnosed with BHD?   
It can be scary to find out that you have a genetic syndrome that raises your risks for cancer and spontaneous pneumothorax, but you may have been living with lung cysts unknowingly for years. Even if you get a renal cancer diagnosis, from what I understand, it is a relatively treatable cancer. It is better to know, than not know. As someone who has had a cancer diagnosis, I am very aware that the longer a cancer is allowed to grow within us, the worse the outcome will often be. Live your life, but keep up with the monitoring. It’s okay to be afraid for a while about what the future might look like, but then, just live. In some ways, I consider my diagnoses as gifts. They remind me to live each day as much in the moment as I can. It may sound trite, but I really don’t take each day for granted anymore. Living in fear of the future isn’t a great way to live. I think that the reason that BHD is rare is that most families aren’t even aware that they have it. Knowledge is power, be grateful that you have the knowledge about this condition.

What do you hope the future looks like for someone living with BHD?
I hope that families can be identified earlier, rather than after a problem arises or an unrelated scan (as in my case) identifies the syndrome. I hope that further research will lead to treatment options or, even better, prevention of the symptoms.  

How can the BHD Foundation better support the BHD community? 
I am very thankful for the quick and informative responses from the BHD Foundation (particularly Katie Nightingale). I believe that the foundation is interested in researching every avenue with BHD for the betterment of the BHD community.  I’ve read several BHD Foundation blog posts and find them enlightening. They are written in an easy-to-read, educational manner. The illustrations are the most helpful and I have sent a few to my extended family.  The only suggestion that I have would be to create a database of BHD expert providers.  Are there any? (*Note from the BHD Foundation: Our website has a map featuring BHD specialists from around the world. We are also happy to help you locate a BHD specialist in your area via email.) I have not found a provider who is familiar with BHD.  It would be nice to have my BHD-related health monitored by an BHD expert who is familiar with the symptoms.  For example, someone who is familiar enough with BHD that could look over my lung CTs, abdominal MRIs, thyroid ultrasounds and skin and help direct me to experts when or if any of these scans looked unusual.  At this time, that role is being filled by my sarcoma and genetic oncologists, not BHD experts.

Interview with Dr Andrew Wagner

What is PEComa?
Perivascular epithelioid cell tumors (PEComa) are rare soft tissue neoplasms that can be benign (no risk of spreading) or malignant (or cancerous, with a risk of spreading). Malignant PEComa are a type of soft tissue sarcoma and can arise anywhere in the body. The cell of origin is unknown, and the name is purely descriptive, reflecting their predilection to be in proximity to small blood vessels (“perivascular”) and shape (cuboidal, or “epithelioid”). About 80% of patients with PEComa are women, for reasons that are not well understood. PEComas express muscle proteins like another type of sarcoma called leiomyosarcoma, and pigment producing proteins that are present in normal melanocytes and melanomas. Because of these features, PEComas are frequently misdiagnosed as leiomyosarcoma or melanoma. Many PEComa have mutations in the genes TSC1 or TSC2 which make proteins that suppress the activity of another protein called mTOR. mTOR normally is tightly regulated and controls the growth and proliferation of cells. When TSC1 or TSC2 are mutated, mTOR is hyperactivated and this can lead to dysregulated growth of cells and formation of tumors. Some other PEComas do not have mutations in TSC1 or TSC2 and instead have a gene rearrangement involving TFE3. A gene rearrangement is when two genes usually on different chromosomes are inappropriately stuck together, leading to changes in when they are expressed or changes in their activity. In the case of PEComa, a gene rearrangement involving TFE3 leads to it being present when it should not be, and TFE3 in turn activates other genes to make proteins that drive the growth of cells. For other PEComas, we do not know what mutations lead to their formation. 

Could you explain the possible association of BHD with PEComa?
There is very little research in this area, but there are some very intriguing possible connections between BHD and PEComa. Some of the published literature is conflicting so it is still pretty confusing. One possible connection is that folliculin, the protein encoded by FLCN (the gene that is mutated in BHD) can cause some modifications on the TFE3 protein that lead to changes of where it is located within a cell. In doing so, it may be able to reduce the activity of TFE3. When FLCN is mutated, though, TFE3 activity may increase and this can lead to tumor formation. The interaction of FLCN and TFE3 may be through mTOR but this remains uncertain.

How common is the association between BHD and PEComa? 
PEComa are ultra-rare tumors, and a very small proportion of patients with PEComa have underlying BHD. Of approximately 120 patients I have seen with PEComa, 3 that are known to have BHD as well.

What research would you like to see done on the association of BHD with PEComa?
We need to understand more between the interplay of FLCN, mTOR, and TFE3, how they regulate each other, and the key pathways that they influence within a cell. Studying the relationship of BHD and PEComa may lead to some fundamental discoveries of each of these diseases and provide key insights into signaling pathways and gene regulation.

What advice would you give to the BHD community? 
There is so much to learn from networks of patients and families with rare diseases, and in bringing together groups of scientists and clinicians to focus on the biology and mechanisms by which tumors arise. Sharing experiences, participating in studies, providing clinical materials such as tumor samples and blood for research are critical to advancing our understanding of disease. Communities of patients can also help educate each other (and doctors!) about credible resources to learn about the disease and identify centers of excellence in clinical care and research.

The BHD Foundation would like to thank both CF and Dr Wagner for their time.

If you would like to share your BHD story please let us know by email.

A Study of BHD in the Swedish Population 

A study following a large number of Swedish individuals with suspected Birt-Hogg-Dubé syndrome (BHD) was recently published. 278 individuals from 78 families were followed through genetic testing and clinical assessment for BHD between 2007 and 2019. In the study there were 125 men, 153 women and the average age was 50 (ranging from 15 to 97 years of age). Of the 278 individuals, 186 (around 2 in every 3 people) had a mutation in the folliculin (FLCN) gene associated with BHD.

Clinical Assessment

This diagram shows how many of the 186 people with a FLCN variant had each of the symptoms associated with BHD.

186 individuals with a FLCN mutation:
88 had fibrofolliculomas
75 had at least one pneumothorax
49 had lung cysts
30 had a kidney tumour
17 had kidney cysts
55 had no symptoms

The authors of the study noted that the number of people with lung cysts was lower than in other studies. They explained that it may be lower because not everyone had a scan of their lungs. Additionally, not every individual in the study had a scan of their kidneys.

The authors also looked at other cancers and found that 9 in186 individuals had colon cancer and/or pre-cancerous colon tumours.

Of the 30 people that had kidney tumours, it was known what type of tumour they had in 22 cases:

  • 8 were hybrid chromophobe/oncocytoma
  • 5 were chromophobe
  • 4 had clear cell kidney cancer
  • 1 was papillary type 2
  • 1 was a hybrid papillary/oncocytoma
  • 1 was an angiomyolipoma
  • 1 was benign (not cancerous)
  • 1 could not be classified

Genetic Assessment

11 different FLCN variants were identified across the 186 individuals. One FLCN variant, c.779+1G>T, was found in 44 of the 78 families in the study. It was initially thought that these families were unrelated. Further testing showed that these families were in fact distantly related. For help on how to interpret your FLCN variant, read our previous toolkit post here.

One of the questions about BHD is whether the FLCN variant you have can predict which symptoms you get. This variant has been reported before and was associated with a range of symptoms. In this study, there was also a range of symptoms reported from the families with this variant:

  • 37 out of the 44 families studied had skin symptoms
  • 33 out of the 44 families studied had lung symptoms
  • 17 out of 44 of the families studied had kidney tumour(s)
  • 7 out of 44 families studied had colon cancer and/or colon polyps

It is estimated that 1 in 3265 people in the Swedish population carry this variant. This indicates the prevalence of BHD is at least 1 in 3265 in the Swedish population. The high frequency of this variant in the cohort studied suggested that it may in fact be a founder mutation. This is a mutation  in the DNA of people who first settled there and from which the population grew.

Summary

This study follows one of the largest cohorts of individuals with BHD. It provides detailed genetic and clinical insights. However, some individuals still had an incomplete medical history. The authors suggested this was due to the lack of clear diagnostic and management guidelines for BHD. This includes the different type of scans you should have and when. Our latest toolkit describes the different scans and when you may have them. Due to the wide variation in the symptoms of BHD seen in different individuals, BHD can prove to be a diagnostic challenge.

The last author of the study, Dr Christos Aravidis (Department of Clinical Genetics, Akademiska Hospital, Uppsala University, Sweden) kindly provided this quote about their work:

Our long term medical follow-up in Sweden, for more than a decade, identified that a unique and specific genetic change constitutes hereditary predisposition for BHD. This implies that BHD may be underdiagnosed due to the syndrome´s diversity. Physicians should be cautious regarding BHD since an early establishment may help to identify people in cancer risk through imaging techniques.

The authors state there is a clear need for up-to-date diagnostic and management guidelines for BHD. The BHD Foundation strongly supports this statement and are actively working towards the development of these guidelines through the BHD Syndrome International Registry (BIRT). We are thrilled that the registry will be launching next week and encourage as many of you to sign up as possible. Sign up to receive updates about the registry, BHD Foundation events and more here.