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A 35-year-old Japanese woman visited our hospital with a pneumothorax incidentally detected in a health screening. Chest radiography revealed slight pneumothorax in the right lung. She was asymptomatic, with 99% oxygen saturation in room air, and no history of smoking and no renal tumours or fibrofolliculomas. However, her father and sister also had a pneumothorax.
Although the pneumothorax was small, chest CT was performed, which revealed multiple thin-walled, variable-sized lung cysts with round, oval and irregular shapes, present bilaterally with lower and medial lung predominance (figure 1A,B). The largest cyst in the right lower lobe contacting the heart was seen abutting or including the proximal portion of the pulmonary vein or artery (figure 1A). These findings are common in Birt-Hogg-Dubé (BHD) syndrome.1 Genetic analysis of her blood revealed a c.1285dupC frameshift mutation in the folliculin (FLCN) gene, consistent with a diagnosis of BHD syndrome.
BHD syndrome is a rare autosomal dominant disorder caused by mutation of germline FLCN mapped in the chromosome 17p11.2 region. It is characterised by fibrofolliculomas, early-onset renal cancers and spontaneous pneumothoraxes caused by lung cysts. The risk of pneumothorax is considerable in patients aged 20–40 years. Lung cysts on chest CT have been described in up to 90% of patients, with a corresponding 50-fold greater risk of pneumothorax than that in the normal population.2 3 A causative gene, FLCN and its interacting partners, FNIP1 and FNIP2, cooperatively play important roles in metabolic pathways including AMP-activated protein kinase-mediated energy AMPK-mediated energy sensing, mTORC1-dependent cell proliferations and Ppargc1a-driven mitochondrial oxidation; the dysregulation of these metabolic pathways triggers aberrant kidney cell proliferations and renal tumourigenesis.4 Therefore, early diagnosis is critical for systematic screening for renal cancers, because of its sevenfold higher risk in these patients, which can lead to a poor prognosis,5 and to refer patients for early genetic counselling and personalised follow-up.
In this case, it was important to perform chest CT, which confirmed a diagnosis of BHD syndrome. Hence, we recommend that physicians perform chest CT at the time of pneumothorax examination in patients with a family history of pneumothorax.
Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder and early diagnosis is critical for systematic screening for renal cancers, which can lead to a poor prognosis.
Lung cysts that can lead to spontaneous pneumothoraxes are the characteristic features of BHD syndrome, but may not always be detected by a chest X-ray examination.
We recommend that physicians perform chest CT at the time of pneumothorax examination in patients with a family history of pneumothorax.
Patient consent for publication Not required.
Contributors KK drafted the manuscript and was responsible for patient care.
Funding The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.