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Update of penetrance estimates in Birt-Hogg-Dubé syndrome.
- Source :
-
Journal of medical genetics [J Med Genet] 2023 Apr; Vol. 60 (4), pp. 317-326. Date of Electronic Publication: 2023 Feb 27. - Publication Year :
- 2023
-
Abstract
- Background: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series.<br />Methods: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN . Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants.<br />Results: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers.<br />Conclusions: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Humans
Male
Female
Aged
Penetrance
Proto-Oncogene Proteins genetics
Tumor Suppressor Proteins genetics
Birt-Hogg-Dube Syndrome genetics
Birt-Hogg-Dube Syndrome pathology
Colonic Polyps
Kidney Neoplasms epidemiology
Kidney Neoplasms genetics
Carcinoma, Renal Cell epidemiology
Carcinoma, Renal Cell genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1468-6244
- Volume :
- 60
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 36849229
- Full Text :
- https://doi.org/10.1136/jmg-2022-109104