Background: Birt–Hogg–Dubé syndrome (BHD), also named Hornstein–Knickenberg syndrome, is a rare autosomal dominant disease characterized by lung cysts, recurrent pneumothoraxes, renal cell carcinoma and skin fibrofolliculomas.
Purpose: This study summarizes the clinical and genetic information of Chinese BHD patients from all available reported cases and explores the relationship between the clinical and genetic spectrum in the hope of improving the prognosis of Chinese BHD patients.
Methods: Relative studies were collected by searching PubMed, Cochrane Library, Embase, OVID medicine, SinoMed, Web of Science, China National Knowledge Infrastructure, Wanfang Data and China Hospital Knowledge Database from January 1, 1977 to December 31, 2021. The search strategy included the following term keys: (Birt–Hogg–Dubé syndrome OR Hornstein-Kinckenberg syndrome OR familial pulmonary cysts OR familial spontaneous pneumothorax OR fibrofolliculomas OR trichodiscomas OR inherited renal cancer syndromes OR FLCN ) AND (Chinese OR China).
Results: In total, 287 Chinese patients from 143 families described in 31 references were included in this article. Chinese BHD patients tended to present more pulmonary symptoms but fewer skin lesions and renal malignancies, which appeared to be atypical when compared with Caucasian patients. The FLCN mutation spectrum among Chinese BHD patients was established with the mutational hot spot c.1285depC/delC as the most frequent mutation. In addition, this mutation spectrum also showed some differences from other races, with a relatively frequent large deletion c.872– 429_1740+1763del (exon 9– 14 deletion) reported only in Chinese individuals but no observation of the two mutational hot spots found in Japanese individuals. We also attempted to establish potential pheno-genotype correlations in Chinese BHD patients, but the results were negative.
Conclusion: To improve the prognosis of BHD patients, physicians need to increase their awareness of BHD by focusing on the family history of pneumothorax as well as skin lesions in patients with lung cysts and promptly advising patients on genetic sequencing.
Keywords: Birt–Hogg–Dubé syndrome, Chinese, FLCN , genetics, phenotype