ERN-GENTURIS: Guidelines on BHD diagnosis, surveillance and management

8 Aug 2024

The first definitive European clinical guidelines for diagnosis and management of BHD

The BHD Foundation is excited to announce the publishing of ERN (European Reference Network)’s first definitive European clinical guidelines for diagnosis and management of Birt-Hogg-Dubé syndrome.

We are especially thankful to our BHD patient representatives, BHD Foundation staff and expert clinicians who contributed to this vital piece of work. We are so proud to be involved in such a landmark project which will improve the lives of those living with BHD syndrome.

The recommendations have been published in the European Journal of Human Genetics and the full guidelines and a plain language summary are available to read.

These clinical recommendations are recommended for the UK and European regions. Each country/region of the world may differ in exactly how to diagnose and manage BHD. Your medical care will be following their own country-specific guidelines if they exist, especially surrounding kidney cancer surveillance and care.

Birt-Hogg-Dubé syndrome

Birt-Hogg-Dubé syndrome, also called BHD, is a rare inherited genetic condition caused by a mutation in the folliculin (FCLN) gene. BHD may cause

Skin bumps called fibrofolliculomas
Lung cysts
Pneumothorax (punctured lung)
Kidney cancer

How many people with BHD get each symptom?

9 in 10 people with BHD will get fibrofolliculomas
9 in 10 people with BHD will get lung cysts. These are mostly asymptomatic but can raise the risk of developing a pneumothorax.
Around 5 in 10 people with BHD will have at least one pneumothorax
Up to 3 in 10 people with BHD will get kidney cancer

Until recently, BHD was thought to be very rare, affecting only about 600 families worldwide. However, recent genomic research into the FLCN gene indicates BHD is in fact much more common than previously thought.

BHD is usually diagnosed via genetic testing. However, until now there have been no definitive guidelines on which clinical signs of BHD would signpost to a clinician that they should actively seek a genetic test for a BHD diagnosis.

Why do we need to establish clinical guidelines for BHD?

For many years BHD patients and their clinicians have not had clear information on how regularly they should be attending BHD check-up and medical care appointments.

This has led to differing standards of care between patients in different countries, and anxiety surrounding questions like how often they should be receiving lifesaving kidney cancer screening.

Additionally, the lack of awareness of BHD in clinical settings has meant testing opportunities are missed and this has led to BHD being underdiagnosed worldwide. Some people are living with BHD but they are undiagnosed, and therefore do not know they have it.

What are the ERN GENTURIS BHD guidelines?

ERN GENTURIS stands for the European Reference Network (ERN) for Rare Genetic Tumour Risk Syndromes (GENTURIS).

They are a clear set of clinical guidelines for diagnosing and managing BHD which is recognised across the UK and Europe. However, no clinician has an obligation to follow these guidelines – they are recommendations only. The ERN GENTURIS BHD guidelines advise European clinicians by:

Setting clear diagnostic criteria for when to test a patient for BHD
Setting a lifelong standard of care for BHD patients

“The guideline can support clinical decision making but should not replace clinical professional assessment and decision making which will be based on the individual needs, person preferences and individual circumstances of each patient.” (Geilswijk et al., 2024)

What do these guidelines help with?

What will these guidelines do for BHD patients?

Raising standard of recommended care with clear surveillance recommendations for the European region.
Helps patients and clinicians understand more about BHD and how it should be diagnosed and managed.
Raises awareness in clinicians about the prevalence and symptoms of BHD which will ultimately lead to more people being tested and diagnosed with BHD.
These guidelines will lead to increased evidence-based research into kidney cancer associated with BHD and clinical surveillance of the condition.

How did the clinicians decide what is the best way to diagnose and manage BHD?

To create these recommendations, the top experts who work with BHD were consulted. They also looked at the existing research and literature surround diagnosis, surveillance and management of BHD. BHD patient representatives and the BHD Foundation were also involved in creating guidelines which we are very proud to be part of.

The evidence has come from multiple specialties, clinical groups and countries, and containing information on a total of several thousand unique BHD patients.

Please note that the full guidelines are intended for clinicians but there is the Plain Language Summary which is aimed at helping patients understand diagnosis and management of BHD.

How can I use the guidelines and plain language summary?

How can this help me and my family?

Guideline Summary Highlights

There are over 25 clinical recommendations in the full clinical guidelines. We have highlighted several below which are common BHD patient queries on:

When family members should seek genetic testing
Kidney cancer surveillance
Whether there is an increased risk of other tumours in BHD

Number	Recommendation
R7.	Predictive genetic testing for familial BHD syndrome is not generally performed until 18 years unless required for specific indications (e.g. clinical management).
R8.	First degree adult relatives of individuals with a likely pathogenic/pathogenic FLCN variant should be offered predictive genetic testing.
R3.	If BHD syndrome is considered as underlying diagnosis, appropriate further investigations, such as skin examination, CT scan of the lungs and/or genetic testing should be initiated.
R13.	Surveillance for kidney cancer should be lifelong.
13a.	Surveillance for kidney cancer should be started at age 20.
13b.	Surveillance for kidney cancer should be conducted every 1-2 years.
R15.	Following the detection of a kidney tumour, the frequency of imaging follow-up should increase to monitor growth rate and plan intervention.
R12.	Currently there is not sufficient evidence of an increased risk for other tumours observed in families with BHD syndrome (e.g. colorectal cancer, malignant melanoma, thyroid cancer, etc).

BHD and wellbeing

Psychological needs of people with BHD must also be considered. Though under-researched, the psychosocial impact of rare conditions is important. Diagnosis delays, family relationships, financial worries and fears for future health can all impact someone’s wellbeing.

The guidelines recommend that clinicians are aware of this and assess needs at each appointment for support as necessary. The Plain Language Summary and full guidelines cover options for support.

References

https://genturis.eu/l=eng/Home.html
Geilswijk, M., Genuardi, M., Woodward, E.R. et al. ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01671-2
Geilswijk M, Genuardi M, Woodward E.R. et al. ERN-GENTURIS-BHD-syndrome-Plain-Language-Summary_UK. ERN GENTURIS; 2024.
Geilswijk M, Genuardi M, Woodward E.R. et al. BHD_guideline_public_v1.pdf. ERN GENTURIS; 202

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