Birt-Hogg-Dubé syndrome: an inherited cause of spontaneous pneumothorax.

(height 1.6 m, body mass index 26.4) was referred to the respirology clinic for assessment of recurrent, bilateral, spontaneous pneumothoraces of unknown cause. She had her first spontaneous pneumothorax at the age of 28 years and had a total of six spontaneous pneumothoraces, distributed bilaterally, over the next 28 years. Repeated surgical interventions were done, including bullectomies and pleural abrasion. Surgical pathology showed subpleural bullae without generalized emphysematous changes or infiltration of smooth muscle cells. Aside from these acute events, the patient was asymptomatic and had no other respiratory symptoms. The patient’s medical history included postnasal drip, dyslipidemia and hypertension. She had no history of other respiratory illness or abnormalities of the skin, kidneys or central nervous system, and she was a lifetime nonsmoker. The patient’s family was of Dutch–Mennonite descent with a strong history of spontaneous pneumothoraces in adulthood, with occurrences in four of seven siblings, the patient’s father and two paternal cousins (Figure 1). The patient’s physical examination was normal except for several small, dome-shaped, pale and flesh-coloured papules on her face, the largest of which appeared on her nose (Figure 2). Biopsies of these papules were consistent with fibrofolliculomas (Appendix 1, available at www .cmaj .ca /cgi /content /full /cmaj .092121/DC1). Skin tags were found on the patient’s neck. A radiograph of the patient’s chest showed no abnormalities, but multiple thin-walled cysts were seen bilaterally in the lungs on a computed tomography (CT) scan (Figure 3). Tests of our patient’s pulmonary function showed that her air flows, lung volumes and diffusing capacity for carbon monoxide were all normal. A diagnosis of Birt–Hogg–Dubé syndrome was suspected on the basis of clinical and radiographic features, as well as evidence of autosomal dominant transmission in the patient’s family. The diagnosis was confirmed with a skin biopsy, and a DNA test on a peripheral blood sample showed a heterozygous mutation in the gene encoding folliculin (FLCN). Subsequent abdominal imaging to assess for renal tumours showed a small (5 mm) lesion in the patient’s right kidney. The lesion is being closely monitored, and has not increased in size on two subsequent CT scans over a period of one year.