Lung Cysts, Spontaneous Pneumothorax, and Genetic Associations in 89 Families with Birt-Hogg-Dubé Syndrome

Abstract

Rationale: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax. Objectives: We evaluated 198 patients from 89 families with BHDS to characterize the risk factors for pneumothorax and genotypepulmonary 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. Measurements and Main 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 ϭ 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 Ͻ 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 ϭ 0.0002). Conclusions: This study indicates that patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.

Birt-Hogg-Dube Syndrome with Multiple Cysts and Recurrent Pneumothorax: Pathological Findings

“…Patients with BHD syndrome have a 50 times greater risk of pneumothorax than do normal people (16), and 24% of 198 patients in 89 family strains developed pneumothorax (17). Another report indicated that 10% of the patients studied had a family history of spontaneous pneumothorax (10), and it is well known that patients with alpha-1 antitrypsin inhibitor defect, Marfan syndrome, Ehlers-Danlos syndrome, tuberous sclerosis, LAM, and cystic fibrosis have a family history of pneumothorax.…”

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene

“…They occur in over 80% of BHD patients. These cysts can be detected usually from the age of 20 years and in about 24% of patients, these cysts are associated with spontaneous pneumothorax Toro et al, 1999;Toro et al, 2007;Zbar et al, 2002). However, one child with a germline FLCN (MIM# 607273) mutation presented with a spontaneous pneumothorax at the age of 7 years (Bessis et al, 2006).…”

Clinical and genetic study of a large Chinese family presented with familial spontaneous pneumothorax

“…Although more males developed pneumothorax (4:2), the distribution of mutation carriers in male and female patients was almost equal (9:8). These characteristics are different from those of primary spontaneous pneumothorax, which typically affects tall, thin males aged between 10 and 30 years (27) (11). As for primary spontaneous pneumothorax, the average rate of recurrence after observation, needle aspiration or tube drainage is about 30% (28), which is lower than the rate of BHD syndrome-related FSP with these treatments.…”

“…Pulmonary cyst is one of the most common manifestations. About 80% of patients have multiple pulmonary cysts, as visible on chest computed tomography (CT), and about 30% of patients develop spontaneous pneumothorax (11). In 2001, the gene responsible for BHD syndrome was mapped to the short arm of chromosome 17 (17p11.2) and was named folliculin gene (FLCN, OMIN 607273, GenBank accession number NM_144997).…”