Individuals with Birt–Hogg–Dubé syndrome (BHDS) may develop fibrofolliculomas, pneumothorax and/or renal cell carcinoma (RCC). Currently, all patients with pathogenic FLCN variants are recommended to have renal surveillance. It has however been suggested that some FLCN variants only cause pneumothorax, which would make surveillance unnecessary in certain cases. This review assesses this possibility. We provide an up-to-date analysis of clinical and genetic features of BHDS. The PUBMED database was systematically searched to find all articles describing patients with pathogenic FLCN variants. The relevant clinical and genetic features of these patients were recorded and analysed. The prevalence of pneumothorax, pulmonary cysts, RCC and characteristic skin lesions in BHDS were 50.9% (n = 1038), 91.9% (n = 720), 22.5% (n = 929) and 47.9% (n = 989), respectively. There was a higher prevalence of pneumothoraces (p < 0.0001) but lower prevalence of dermatological findings (p < 0.0001) in patients from East Asia compared to North America or Europe. Of the 194 pathogenic FLCN variants, 76 could be defined as ‘pneumothorax-only’. Pneumothorax only pathogenic variants (POPVs) were distributed throughout the gene, and there were no statistical differences in variant type. The majority of POPVs (65/76) affected no more than three individuals. Individuals with ‘POPVs’ also tended to be younger (45 vs. 47 years, p < 0.05). Many apparent POPVs in the literature could result from variable expressivity, age-related penetrance and other confounding factors. We therefore recommend that all individuals found to carry a pathogenic FLCN variant be enroled in lifelong surveillance for RCC.

患有 Birt-Hogg-Dubé 综合征 (BHDS) 的个体可能会发展为纤维毛囊瘤、气胸和/或肾细胞癌 (RCC)。目前，建议所有携带致病性FLCN变异的患者进行肾脏监测。然而，有人提出，某些FLCN变体只会引起气胸，这在某些情况下会使监测变得不必要。本综述评估了这种可能性。我们提供 BHDS 临床和遗传特征的最新分析。系统搜索 PUBMED 数据库以找到所有描述致病性FLCN患者的文章变体。记录和分析这些患者的相关临床和遗传特征。BHDS中气胸、肺囊肿、肾细胞癌和特征性皮肤病变的患病率分别为50.9%（n  = 1038）、91.9%（n  = 720）、22.5%（n  = 929）和47.9%（n  = 989）。 与北美或欧洲相比，东亚患者的气胸患病率较高 ( p  < 0.0001)，但皮肤病学发现的患病率较低 ( p < 0.0001)。194 种致病性FLCN变异，76 可以定义为“仅气胸”。仅气胸致病变异（POPV）分布在整个基因中，变异类型没有统计学差异。大多数 POPV (65/76) 影响的人不超过三个。患有“POPV”的个体也往往更年轻（45 岁与 47 岁，p  < 0.05）。文献中许多明显的 POPV 可能是由可变的表现力、与年龄相关的外显率和其他混杂因素造成的。因此，我们建议所有被发现携带致病性FLCN变异的个体都参与 RCC 的终身监测。