Birt-Hogg-Dubé（BHD）综合征是一种罕见的遗传综合征，由FLCN基因中的致病或可能致病的生殖细胞变异所致。患有BHD综合征的患者具有发生纤维-毛囊瘤、肺囊肿、气胸和肾细胞癌的增加风险。关于是否将结肠息肉添加到诊断标准中存在争议。以往的风险估计主要基于小规模临床病例系列。对招募携带FLCN致病或可能致病变异的家族的研究进行综合评估。从这些研究中请求家谱数据并进行汇总。使用分离分析估计FLCN致病变异携带者各表现形式的累计风险。我们的最终数据集包含204个家族，对BHD的至少一个表现形式具有信息性（67个家族表现为皮肤表现，63个家族表现为肺，88个家族表现为肾癌，29个家族表现为息肉）。到70岁时，携带FLCN致病变异的男性患者肾肿瘤的风险估计为19％（95％CI 12％至31％），肺涉及的风险估计为87％（95％CI 80％至92％），皮肤病变的风险估计为87％（95％CI 78％至93％），而女性承载者肾肿瘤的风险估计为21％（95％CI 13％至32％），肺涉及的风险估计为82％（95％CI 73％至88％），皮肤病变的风险估计为78％（95％CI 67％至85％）。到70岁时，携带FLCN致病变异的男性患者结肠息肉的累计风险为21％（95％CI 8％至45％），女性患者的风险为32％（95％CI 16％至53％）。这些基于大量家族的更新渗透率估计对于BHD综合征的遗传咨询和临床管理非常重要。©作者（或其雇主）2023。不可进行商业复制。有关权利和权限，请参见BMJ的发表。

Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series.A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN. Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants.Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers.These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.