Birt-Hogg-Dubé Syndrome (BHDS) Specimens

Bay Biosciences provides high quality, clinical grade bio-samples, cryogenically preserved biopsy tissue, FFPE blocks, sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid specimens from patients diagnosed with Birt-Hogg-Dubé Syndrome (BHDS).

The sera (serum), plasma and PBMC biofluid samples are processed from patient’s peripheral whole-blood using customized processing protocols. The Birt-Hogg-Dubé Syndrome (BHDS) bio-specimens are collected from unique patients diagnosed with Birt-Hogg-Dubé Syndrome (BHDS) and are provided to a valued pharmaceutical customer for translational research, genomics, proteomics and biomarker research, drug discovery and development.

Birt-Hogg-Dubé Syndrome (BHDS) Overview

Birt–Hogg–Dubé syndrome also known as Hornstein–Knickenberg Syndrome is a rare autosomal dominant genetic disorder, it is an inherited condition characterized by the development of benign tumors on the head, face and upper body. Birt–Hogg–Dubé Syndrome is also known as fibrofolliculoma with trichodiscoma and acrochordon.

Patients with Birt-Hogg-Dubé Syndrome are at increased risk of developing colon or kidney cancer as well as spontaneous pneumothorax (lung collapse) due to pulmonary (lung) cysts and noncancerous tumors of the hair follicles called fibrofolliculomas.

The benign skin tumors involved in Birt-Hogg-Dube Syndrome (BHDS) are:

• Fibrofolliculoma- Tumor developing in hair follicles
• Trichodiscoma- Tumor of the hair disc
• Angiofibroma- Vascular Tumor
• Acrochordon- Skin tags

Symptoms of Birt-Hogg-Dubé Syndrome (BHDS)

Painless, small, papular skin lesions develop gradually over the scalp, face, neck, chest and back in BHDS patients. Lesions usually develop at around age 30 or 40 years, although they have been found in younger patients also, and they are not always present in people with the abnormal BHD gene. The symptoms of Birt-Hogg-Dube Syndrome seen in each family are unique, and can include any combination of the three symptoms.

Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of the patients with BHDS over the age of 40. Pulmonary cysts are equally common in BHDS patients (around 85% of the patients). Only around 25% of people with BHD eventually experience a collapsed lung (spontaneous pneumothorax). Kidney tumors, both cancerous and benign, occur in 15–30 percent of the BHDS patients, the associated kidney cancer are often rare hybrid umors.

• Fibrofolliculomas (also called trichodiscomas) are small (2-4 mm), white-to-flesh colored, smooth, dome-shaped bumps.
• Acrochordons or skin tags are small, soft 1-2 mm bumps that look like a wart with a thin neck.
• There may be anywhere on the patients body from two to many hundreds of lesions.
• Once developed, skin lesions are permanent.

Oral mucosal polyps, collagenomas, angiolipomas, and deforming lipomas may also form in the BHDS patients.

Causes of Birt-Hogg-Dubé Syndrome (BHDS)

Birt–Hogg–Dubé syndrome (BHDS) is caused due to a mutation in the BHD or FLCN gene on chromosome 17p12-q11.2 encoding a protein called folliculin. It is not known why this mutation occurs. Though its function is not fully understood, it appears to be a tumor suppressor gene that restricts cell growth and division. The syndrome is an autosomal dominant condition meaning half of an affected person’s children have a risk of inheriting the mutation. Versions of FLCN gene have been found in other animals, including fruit flies, German shepherds, rats and mice.

Birt–Hogg–Dubé syndrome can manifest similarly to other diseases, which must be ruled out when making a diagnosis. These include tuberous sclerosis, which causes skin lesions similar to fibrofolliculomas, and Von Hippel-Lindau disease, which also causes hereditary kidney cancers.

FLCN gene creates a protein called folliculin that has two isoforms. It appears to act as a tumor suppressor and is expressed strongly in the skin, distal nephrons and Type-1 pneumocytes. It has also been found in the parotid gland, brain, breast, pancreas, prostate and ovaries. Tumor suppressors normally prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to the formation of noncancerous and cancerous tumors.

The kidney tumors in Birt–Hogg–Dubé syndrome (BHDS) patients range from benign oncocytomas to malignant renal cell carcinomas (cancer) including chromophobe, clear cell or papillary subtypes. Hybrid tumors may also sometimes develop in the kidney of a Birt–Hogg–Dubé syndrome (BHDS) patients. The typical skin lesions are called fibrofolliculomas. Fibrofolliculomas are characterized by a circumscribed proliferation of collagen and fibroblasts surrounding distorted hair follicles from which basaloid cells protrude into the surrounding fibromucinous stroma.

Other characteristic of Birt–Hogg–Dubé syndrome (BHDS) patients skin anomalies are trichodiscomas and acrochordons. Dermatological manifestations of BHDS usually develop in the third and fourth decades of life and persist indefinitely. Moreover, cutaneous manifestations usually have an earlier onset than associated kidney tumors. The pulmonary cysts are characterized by cystic dilatation of alveolar spaces, ranging from microscopic foci to a few millimeters in diameter. The thin-wall cysts are lined by cuboidal epithelium. The cysts rupture under pressure of inhalation, which leads to pneumothorax.

Etiology of Birt–Hogg–Dubé syndrome (BHDS)

BHD syndrome is transmitted in an autosomal dominant fashion. A potential causative gene, FLCN, has been located on chromosome 17p11.2. This BHD gene encodes folliculin and although the function of the BHD gene product is still unknown, it is believed to be a component of the mTOR pathway (like other hamartoma syndrome-related proteins) and play a role in the development of renal neoplasms and possibly other associated lesions.

Diagnostic methods of Birt–Hogg–Dubé syndrome (BHDS)

Diagnosis relies on recognition of the clinical manifestations, together with histological analysis to confirm the presence of the trichodiscomas, perifollicular fibromas and fibrofolliculomas associated with Birt–Hogg–Dubé syndrome (BHDS). The diagnosis can be confirmed by detection of DNA mutations
in the BHDS, FLCN gene.

Differential Diagnosis Birt–Hogg–Dubé Syndrome (BHSD)

The differential diagnosis of the multiple firm papules of Birt–Hogg–Dubé syndrome (BHDS) is dependent on whether the skin lesions are epithelial, mesodermal or mixed in origin. BHD patients and their relatives should seek genetic counseling and testing if possible.

Management and treatment of Birt–Hogg–Dubé Syndrome (BHDS)

There is no specific medical treatment for the dermatologic manifestations of Birt–Hogg–Dubé Syndrome (BHDS) patients. The definitive treatment for solitary perifollicular fibromas is surgical removal. In addition, dermabrasion and electro-desiccation have been suggested as treatment options, but lesions may recur. Patients with BHD should be screened and pulmonary, renal, and gastrointestinal findings should be managed.

Prognosis

The prognosis for patients with Birt–Hogg–Dubé Syndrome (BHDS) is dependent on the degree of

internal involvement and the type of kidney tumor involved.

Detailed clinical data, FLCN molecular genetic test, elevated biomarker levels, genetic and metabolic information, tumor tissue biopsy, pathology annotations associated with the Birt-Hogg-Dubé Syndrome (BHDS) patient’s specimens is provided to a valued customer for drug discover, development and research. The Birt-Hogg-Dubé Syndrome (BHDS) sera (serum), plasma and PBMC biofluid samples are processed from patients peripheral whole-blood using customized collection and processing protocols provided by the researcher.

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