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Review
. 2024 Dec;32(12):1542-1550.
doi: 10.1038/s41431-024-01671-2. Epub 2024 Jul 31.

ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome

Marianne Geilswijk  1 , Maurizio Genuardi  2   3 , Emma R Woodward  4 , Katie Nightingale  5 , Jazzmin Huber  5 , Mia Gebauer Madsen  6 , Dieke Liekelema-van der Heij  5 , Ian Lisseman  5 , Jenny Marlé-Ballangé  7 , Cormac McCarthy  8 , Fred H Menko  9 , R Jeroen A van Moorselaar  10 , Elzbieta Radzikowska  11 , Stéphane Richard  12 , Neil Rajan  13 , Mette Sommerlund  6 , Maria T A Wetscherek  14 , Nataliya Di Donato  15 , Eamonn R Maher  16   17 , Joan Brunet  18
Affiliations
Review

ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome

Marianne Geilswijk et al. Eur J Hum Genet. 2024 Dec.

Abstract

Birt-Hogg-Dubé syndrome (BHD syndrome) is an autosomal dominant multisystem disorder with variable expression due to pathogenic constitutional variants in the FLCN gene. Patients with BHD syndrome are predisposed to benign cutaneous fibrofolliculomas/trichodischomas, pulmonary cysts with an associated risk of spontaneous pneumothorax, and renal cell carcinoma. A requirement for updated International consensus recommendations for the diagnosis and management of BHD syndrome was identified. Based on a comprehensive literature review and expert consensus within the fields of respiratory medicine, urology, radiology, dermatology, clinical oncology and clinical genetics, updated recommendations for diagnosis, surveillance and management in BHD syndrome were developed. With the widespread availability of FLCN genetic testing, clinical scenarios in which a diagnosis should be considered and criteria for genetic testing were defined. Following a clinical and/or molecular diagnosis of BHD syndrome, a multidisciplinary approach to disease management is required. Regular renal cancer surveillance is recommended in adulthood and life-long, but the evidence base for additional tumour surveillance is limited and further research warranted. Recommendations for the treatment of cutaneous, pulmonary and renal manifestations are provided. Awareness of BHD syndrome needs to be raised and better knowledge of the clinical settings in which the diagnosis should be considered should enable earlier diagnosis. Further details, including areas for future research topics are available at: https://www.genturis.eu/l=eng/Guidelines-and-pathways/Clinical-practice-guidelines.html .

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Conflict of interest statement

Competing interests: All members of the ERN GENTURIS BHD Guideline Group, including the Core Working Group, have provided disclosure statements on all relationships that they have that might be perceived to be a potential source of a conflict of interest. Core Working Group patient representatives KN and JH were employed by the Myrovlytis Trust. MGM reports receipt of honoraria or consultation fees from Ipsen. CMC reports receipt of research funding from Boehringer Ingelheim, honoraria or consultation fees from Savara Inc, Theravance, AI Therapeutics, Roche, Aerogen as well as grants from Health Research Board, LAM Foundation and Enterprise Ireland. NR reports participation in a company sponsored speaker’s bureau from Takeda UK. MTAW reports receipt of honoraria or consultation fees from Microsoft. All participants of the ERN GENTURIS BHD syndrome Delphi survey have provided disclosure statements on all relationships that they have that might be perceived to be a potential source of competing interests. Patrick Benusiglio reports receipt of honoraria or consultation fees from AstraZeneca, Bristol Myers Squibb and Merck Sharp & Dohme. Raphael Borie reports receipt of grants/research support from Roche and Boehringer Ingelheim, as well as receipt of honoraria or consultation fees from Roche, Boehringer Ingelheim and Sanofi. Jesper Rømhild Davidsen reports receipt of honoraria or consultation fees from Boehringer Ingelheim. Arndt Hartmann reports receipt of grants/research support from AstraZeneca, Biocartis, Biontech, Cepheid, Gilead, Illumina, Janssen, Nanostring, Novartis, Owkin, Qiagen, QUIP GmbH, Roche and Sanofi, as well as receipt of honoraria or consultation fees from Abbvie, AstraZeneca, Biocartis, Biontech, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Gilead, Illumina, Ipsen, Janssen, Lilly, MSD, Nanostring, Novartis, Qiagen, QUIP GmbH, Roche, Sanofi and 3DHistotech. Arjan C. Houweling reports receipt of a research grant from the Myrovlytis Trust. Stefan J. Marciniak reports receipt of grants/research support from the Myrovlytis Trust, Asthma+Lung UK, Alpha 1 Foundation, the Medical Research Council (MRC) UK, and the Engineering and Physical Sciences Research Council (EPSRC). Maria Molina-Molina reports receipt of grants/research support from Boehringer Ingelheim and Roche, as well as receipt of honoraria or consultation fees from Ferrer, Chiesi, Boehringer Ingelheim, Roche and Esteve-Teijin. Charles Van Praet reports receipt of honoraria or consultation fees from Astellas, IPSEN and Baxter. Robin de Putter reports receipt of honoraria or consultation fees from AstraZeneca. Lore van Riel reports receipt of a research grant from the Myrovlytis Trust. Jacobo Sellarés Torres reports receipt of grants/research support from Roche and Boehringer Ingelheim, receipt of honoraria or consultation fees from Boehringer Ingelheim, as well as participation in a speaker’s bureau sponsored by Boehringer Ingelheim. Grant D. Stewart reports receipt of grants/research support from AstraZeneca and Pfizer, receipt of honoraria or consultation fees from Pfizer, Merck, EUSA Pharma and Eisai, as well as participation in a speaker’s bureau sponsored by Eisai.

Comment in

References

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