Birt hogg dube 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 pneumothorax, 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.
It is a rare complex genetic skin disorder (genodermatosis) characterized by the development of skin papules generally located on the head, face and upper torso. These benign (noncancerous) tumors (hamartomas) of the hair follicle are called fibrofolliculomas. BHD syndrome also predisposes individuals to the development of benign cysts in the lungs, repeated episodes of a collapsed lung (pneumothorax), and increased risk for developing kidney neoplasia. BHD syndrome is caused by alterations (mutations) in the FLCN gene (alias BHD) and is inherited as an autosomal dominant trait.
Birt-Hogg-Dubé syndrome (also known as BHD) is a hereditary condition named after the three Canadian doctors that first described it in 1977 – Arthur R. Birt, Georgina R. Hogg, and William J. Dubé (1).
At first, BHD was thought to be a skin condition after skin lesions were found on the faces and necks of several members of an extended family. It is now known that BHD can also cause lung cysts, collapsed lungs, and kidney cancer. BHD mainly affects adults with lung cysts and skin lesions usually appearing in a person’s 20s and 30s and kidney cancer occurring at an average age of 50.
There is no typical BHD patient. Someone with BHD may get one, two or all three of the symptoms, and no two people will be the same – even if they’re from the same family. At the moment there is no way of predicting who will get which symptoms, but roughly (2):
Birt hogg dube syndrome is caused by mutations in the Folliculin gene, and only a genetic test can find mutations. Having the symptoms of BHD suggests that you might have BHD, but there are other diseases that can also cause these symptoms, so the only way to definitely diagnose BHD is by gene sequencing.
Birt hogg dube is a rare disease with only roughly 600 reported families worldwide, however many researchers believe it is under-diagnosed (3). Because BHD is so rare, many doctors have not heard of it, so there are probably many more families with this disease that haven’t been diagnosed.
Researchers are currently investigating the function of the Folliculin protein and how a mutation in this gene causes the symptoms of BHD. The ultimate aim of scientific research is to develop treatments to prevent or cure BHD syndrome.