BHD Syndrome at a Rare Lung Disease Clinic in China 

The first study of Birt-Hogg-Dubé Syndrome (BHD) in China was published in 2008. However, by the end of 2021 there were still only 221 Chinese patients reported in the literature. Given the large population of China, it is very likely that BHD is highly underdiagnosed. In 2019, a Rare Lung Disease Clinic was set up at The First Affiliated Hospital of USCT in Anhui province, China. The aim of the clinic was to improve the diagnosis and management of patients with rare lung diseases including BHD. 

Clinical Features 

This recent study highlights the clinical and genetic features of 50 people from 31 families diagnosed with BHD from January 2017 to December 2021. The average age at diagnosis was 47.4 years (ranging from 18 to 76 years of age). The clinical features of these patients were as follows (please note that not every individual underwent every scan or examination): 

  • 48 out of 49 people had lung cysts. 
  • 27 out of 50 people had at least one collapsed lung. 
  • 29 out of 50 people reported a family history of collapsed lungs. 
  • 32 out of 47 people had skin symptoms defined as multiple, skin-coloured papules.  
  • 2 out of 41 people had kidney cancer. 
  • 4 out of 41 people had a type of non-cancerous kidney tumour called angiomyolipoma. 

Focusing on the lung symptoms in more detail, it was reported that the average number of collapsed lungs a person had was 2. The maximum number an individual had was 7. There were 3 episodes of lung collapses on both lungs at the same time (bilateral). Lung cysts were the most common sign. Most people had more than 20 cysts in both lungs which ranged between 1 and 5 cm and were irregular in shape. In all cases, the cysts were found towards the bottom of the lungs, a typical feature of BHD.  

Of interest, this is one of the few reports from East Asia which reports a high number of people with skin symptoms. However, only 9 people underwent a biopsy to confirm the type of skin manifestation. 2 were reported to be fibrofolliculomas. 1 was confirmed as a trichodiscoma and the others were confirmed to be epidermoid cysts. The authors of the study discussed the differences seen in their study compared with other studies. They suggested that the skin symptoms may have been overlooked previously. Evidence shows these are increasing reported in newer studies. 

The authors also note the low incidence of kidney cancer in this group. They comment that this may be due to selection bias since nearly everyone in the study was recruited through the rare lung disease clinic and not a kidney clinic. However, they also do not exclude the role genetics may play. The low incidence of kidney cancer in East Asian BHD patients has been reported before.  

Genetics 

45 individuals underwent genetic testing for BHD (the rest were diagnosed clinically). Of these 45 people, a mutation in folliculin (FLCN) was found in 44. The most common mutations were c.1285dup, c.1285del, which are generally the most reported FLCN mutations. Find out more about understanding genetic mutations here

Management of BHD 

The authors compared the recurrence rate of collapsed lungs between those who had surgery and those who had a more conservative treatment (e.g. a chest drain). Reoccurrence was more common in people who had chest drains.   
Only 15 patients underwent annual follow-up in the study. The authors discussed that this could also contribute to the low incidence of kidney cancer seen. Ideally, people with BHD should get regular kidney scans so that any kidney cancer can be found and treated quickly.  

Summary 

This study represents, so far, the largest cohort of individuals with BHD in the Chinese population. Although lung symptoms were still the most reported, there was a high number of individuals with skin symptoms. The Rare Lung Disease Clinic is a multidisciplinary team made up of different specialists. These include a radiologist, pathologist, dermatologist, urologist and thoracic surgeon, as well as lung specialists. You can read more about the different types of healthcare professionals here. The authors state their multidisciplinary approach is the best for the diagnosis and management of BHD. They saw an increase in the number of people diagnosed with BHD year on year after establishing the clinic. In the future, the authors would like to extend their study across different centres to be able to recruit a larger number of individuals. 

At the BHD Foundation, we were excited by this approach and were encouraged that it has led to an increase in BHD diagnoses over the last 3 years. We look forward to seeing future studies in China and other East Asian countries to improve our understanding of BHD. We hope to establish a worldwide network to enable people with BHD to access the best possible care. 

On June 30th, we are celebrating World Pneumothorax Day. We will be raising awareness of the genetic causes of collapsed lungs. We would love for you to join us and help spread the word using our social media toolkit.  

The First Genetic Study of BHD in India

At the BHD Foundation, we support individuals with BHD worldwide. Much of the research on BHD has been done in Europe and the US and so we were excited to see the first study of BHD in India. The clinical and genetic features of 31 individuals with BHD from 15 families were studied. The individuals had been diagnosed based on their clinical symptoms rather than through genetic testing. 74 “asymptomatic” family members were also included in the study. These people did not have any BHD symptoms.

Clinical Features

  • 30 out of 31 individuals had lung symptoms (lung cysts and/or collapsed lungs).
  • 10 out of 31 individuals had fibrofolliculomas (skin bumps).
  • 3 out of 31 individuals had chromophobe kidney cancer.
  • The average age of onset of the first symptom was 44 years.

Reports from Western countries generally find the skin bumps to be the most common BHD symptom. However here, and in other studies from Eastern countries, they are reported less commonly. Instead, lung cysts and collapsed lungs are more frequent. The differences between the symptoms seen in these populations are currently unknown. It could be due to genetic differences or environmental factors. Another option is that the skin symptoms are simply less commonly reported or diagnosed. Increasing the number of reports like this one will help us address this question in the future.

Given the lung symptoms of BHD were the most common in this study, the authors looked more closely at these symptoms. 27 out of 31 individuals had experienced a pneumothorax (collapsed lung). 9 of these people had recurring pneumothoraces. The age of onset of a collapsed lung ranged from 15 to 59. The authors calculated the probability that an individual would have repeated collapsed lungs and found that the age at which the first collapsed lung occurred was an important factor. They found that people who had recurring pneumothoraces had their first collapsed lung at a younger age than those who only had a single collapsed lung.

Genetics

A mutation in folliculin (FLCN, the gene associated with BHD) was found in 19 of the 31 individuals from 10 of the 15 families.

11 of the 19 patients (from 5 families) had the same mutation: c.1285delC. This is the most common FLCN mutation and known to be a ‘hotspot’ for mutations in the FLCN gene. Our previous toolkit post helps you find out more about understanding genetic test results. All these individuals had lung cysts or collapsed lungs. The remaining families each had different mutations, of which 2 had not been previously reported.

A mutation in FLCN was also found in 16 of the 74 asymptomatic family members. The authors noted that the average age of these individuals was 29 and so they may still develop symptoms in the future.

A mutation in FLCN could not be found in 12 individuals from 5 families, even though they had BHD symptoms. There could be 2 possible explanations for this. The first is that there is a mutation in FLCN that could not be detected using the methods used in this study. The second is that there is no mutation in FLCN and perhaps another, unknown gene, is responsible for the symptoms seen in these individuals. Further work using a more sensitive type of sequencing would need to be performed to determine which explanation is correct. It would also be interesting to expand upon this work in the future to include more people with BHD. This would strengthen the current data and could help inform future diagnosis guidelines in different countries.

We are excited to see future reports from different countries reporting the clinical and genetic features of BHD. If you are an individual with BHD, or a clinician interested in BHD you can add yourself to our BHD Worldwide map.

Facebook Live Discussion with Pulse Infoframe

We recently held a Facebook Live to discuss our BHD Syndrome International Registry (BIRT). We discussed the benefits of signing up to BIRT and how you can help shape the future of BHD research. We were joined by our partners Pulse Infoframe who shared information on the privacy and security of their platform. We were also excited to be able to share some of the first results from the first 2 months of data collection.

Watch the recording of it below or download the transcript here.

Join the registry by signing up here.

How does Folliculin Regulate mTORC1 Activity?

Our cells need to be able to sense and respond to our body’s needs. Mechanistic target of rapamycin complex 1 (mTORC1) is a protein in our cells that acts as a central hub for this sensing ability. It can sense several inputs and can turn on or off different pathways (branches) in response to these stimuli. It is often described as a single on/off switch however this process is likely to be far more complicated than that. A recent paper by Li et al., has described specific regulation of different mTORC1 branches. 

Why is this relevant to Birt-Hogg-Dubé Syndrome (BHD)? BHD is caused by mutations in the gene folliculin (FLCN). The authors of the study found that FLCN was capable of specifically modifying mTORC1 function. It was able to turn on a specific branch of mTORC1 signalling without effecting the other pathways.

It has been shown previously that one of these mTORC1 branches is important for kidney tumour development in BHD. This pathway controls the activation of 2 related proteins called TFE3 and TFEB. These proteins are known as transcription factors. When they are turned on, they move from the cytoplasm to the nucleus (where DNA is located) and can trigger the expression of other proteins in our cells. Normally, when mTORC1 is active it modifies TFE3 and TFEB, so they stay in the cytoplasm (see the diagram below). This process is dependent on FLCN. So when cells are lacking FLCN, mTORC1 can no longer keep TFE3 and TFEB in the cytoplasm and they move to the nucleus. This results in expression of proteins that wouldn’t happen in cells containing FLCN and can drive tumour growth.  

The authors of this present study have built upon this knowledge to understand how FLCN is able to influence TFE3 signalling through mTORC1 without modifying other branches. They found that FLCN activates another protein called RagC. RagC physically recruits TFE3 to an area of the cell where it can be turned off by mTORC1. TFE3 is kept in the cytoplasm and unable to move to the nucleus. The researchers made a special form of RagC that was always on and didn’t need FLCN to activate it. They saw that this active form of RagC could turn off TFE3 signalling in cells that were lacking FLCN. This meant that this whole process is dependent on the activity of FLCN. This process could also happen without affecting any of the other functions of mTORC1. Additionally, when TFE3 is turned on it can drive the expression of other proteins that further activate mTORC1. This is known as a positive feedback loop and results in the hyperactivation of mTORC1.

Previous work has shown conflicting roles for mTORC1 in BHD. In some models with reduced FLCN, mTORC1 activation was shown to be reduced. However, in samples derived from BHD kidney tumours, hyperactivation of mTORC1 was observed. The mechanism proposed in this study has helped address this conflicting evidence. Activity of mTORC1 is often measured by looking at proteins that are turned on or off by mTORC1. The variations in these models could be explained by different researchers looking at proteins in different branches of mTORC1 signalling. For example, if one researcher looked at TFE3 activity they may have concluded that mTORC1 activation was reduced. However, if another group looked at a protein in another branch of mTORC1 signalling, they may have found hyperactivity of mTORC1.

This work is important because it helps us better understand how loss of FLCN can potentially lead to cancer development. Knowing which proteins FLCN interacts with, and the effect of that interaction can help guide the development of new anti-cancer treatments.

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.

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.