Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome.
BACKGROUND
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax.


OBJECTIVE
We evaluated 198 patients from 89 families with BHDS to characterize the risk factors for pneumothorax and genotype-pulmonary associations.


METHODS
Helical computed tomography scans of the chest were used to screen for pulmonary abnormalities. BHD mutation data were used for genotype-pulmonary associations. We examined the relationship of pneumothorax with categorical parameters (sex, smoking history, and lung cysts) and continuous parameters (number of cysts, lung cyst volume, and largest cyst diameter and volume). Logistic regression analyses were used to identify the risk factors associated with pneumothorax.


RESULTS
Twenty-four percent (48/198) of patients with BHDS had a history of pneumothorax. The presence of lung cysts was significantly associated with pneumothorax (p = 0.006). Total lung cyst volume, largest cyst diameter and volume, and every parameter related to the number of lung cysts were significantly associated (p < 0.0001) with pneumothorax. A logistic regression analysis showed that only the total number of cysts in the right parenchymal lower lobe and the total number of cysts located on the pleural surface in the right middle lobe were needed to classify a patient as to whether or not he or she was likely to have a pneumothorax. Exon location of the BHD mutation was associated with the numbers of cysts (p = 0.0002).


CONCLUSIONS
This study indicates that patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.
Toro
Jorge R
JR
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892-7231, USA. torojo@exchange.nih.gov
Pautler
Stephen E
SE
Stewart
Laveta
L
Glenn
Gladys M
GM
Weinreich
Michael
M
Toure
Ousmane
O
Wei
Ming-Hui
MH
Schmidt
Laura S
LS
Davis
Lewis
L
Zbar
Berton
B
Choyke
Peter
P
Steinberg
Seth M
SM
Nguyen
Dao M
DM
Linehan
W Marston
WM
D001994:Bronchogenic Cyst / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011030:Pneumothorax / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D012871:Skin Diseases / Q000453:epidemiology / Q000235:genetics*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins