Birt–Hogg–Dubé syndrome

Abstract

Birt–Hogg–Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.

Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families

“…with the mammalian target of rapamycin(mTOR) and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways [2][3][4][5]. Over 600 families with BHD have been reported worldwide in the past 40 years, mainly Caucasians in Europe and USA.…”

Birt-Hogg-Dubé Syndrome in Chinese Patients: A Literature Review of 120 Families

“…Due to the high prevalence of lung cysts in adult patients with BHDS, spontaneous pneumothorax has been found to be a common presentation 3 . In our study, 71% of con rmed patients had at least one episode of pneumothorax and nearly 85% of them had a family history of pneumothorax.…”

“…Subsequent study revealed that the prevalence of renal tumors in patients with BHD was 34% with a mean age at diagnosis of approximately 50 years 33 . Chromophobe renal carcinoma was the most common histological type of renal cancer, followed by hybrid oncocytic/chromophobe tumor 3,7 . Similar ndings were reported in a recent largest study including 312 Japanese cases from 120 different families 7 .…”

“…Skin lesions were a common feature of BHDS in Caucasians, in whom it is found in about 80%~90% 3,34 . Characteristic lesions brofolliculomas and trichodiscomas are important clues in recognizing BHDS, but the patients in Asian countries seem to have lower prevalence of skin lesions 3,7,29 . Previous study demonstrated skin lesions developed in less than 30% in Chinese patients 26 , similar to the current study.…”

“…Birt-Hogg-Dubé syndrome (BHDS, OMIM#135150) is a rare autosomal dominant inherited disorder, rst described in 1977, featured by lung cysts, spontaneous pneumothorax, skin lesions ( brofolliculomas and trichodiscomas) and renal tumors 1 . It is caused by germline mutations in the folliculin (FLCN) gene, which is located on chromosome 17p11.2 and encodes a 579-amino acid protein with tumor suppressor function, and interacts with the mammalian target of rapamycin(mTOR) and adenosine monophosphateactivated protein kinase (AMPK) signaling pathways [2][3][4][5] . Over 600 families with BHD have been reported worldwide in the past 40 years, mainly from Europe and USA.…”