Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Br J Cancer. 2011 Dec 6;105(12):1912-9. doi: 10.1038/bjc.2011.463.
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD.
In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families.
Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%) and 29% (95% minimal confidence interval: 9-49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas.
We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.
Birt-Hogg-Dubé（BHD）综合征是一种常染色体显性遗传病，由胚系 FLCN 突变引起，其特征为纤维毛囊瘤、气胸和肾癌。BHD 的肾癌风险、癌症表型和气胸风险尚未完全阐明。本研究的主要重点是评估 BHD 的肾癌风险、肾肿瘤的组织学亚型和气胸风险。
本研究我们展示了来自 35 个 BHD 家族的 115 名 FLCN 突变携带者的临床数据。
在 14 名发生肾癌的 FLCN 突变携带者中，有 7 名发病时年龄<50 岁，或有多发性/双侧肿瘤。5 名有症状的患者发生了转移性疾病。2 例早期病例通过监测诊断。大多数肿瘤表现出嗜酸性变异的透明细胞癌和嫌色细胞癌的特征。肾癌和气胸的估计外显率分别为 16%（95%最小置信区间：6-26%）和 29%（95%最小置信区间：9-49%），在 70 岁时。在未发现 FLCN 突变的家族中，最常见的诊断是家族性多发性盘状纤维瘤。
我们证实了临床上定义的 BHD 家族中 FLCN 突变的高检出率，发现 FLCN 突变携带者的肾癌终生风险显著增加，达到 16%。14 名患者中有 5 名发生了转移，肿瘤组织学对 BHD 不具有特异性。我们发现气胸风险为 29%。我们讨论了我们的研究结果对 BHD 的诊断和管理的影响。
