FaCD Online Syndrome Fact Sheet

Last updated: 13 May 2010

Name: Birt-Hogg-Dubé syndrome

Synonym: BHD, Fibrofolliculomas with Trichodiscomas and Acrochordons, incl.: Hornstein-Knickenberg syndrome, Perifollicular Fibromatosis

Mode of Inheritance: AD

Genes

FLCN, mapped to 17p11.2

Tumor features

acrochordons
fibrofolliculomas
perifollicular fibromas
renal cell cancer, chromophobe
renal cell cancer, clear-cell (Grawitz tumor)
renal cell cancer, papillary
renal oncocytoma
trichoblastoma
trichodiscomas

Tumor features (possible)

breast cancer
colon cancer
colorectal polyps
dermatofibrosarcoma protuberans
Hodgkin disease (Hodgkin's lymphoma)
laryngeal cancer
leiomyoma
leiomyosarcoma
melanoma, cutaneous
oropharyngeal cancer
parotid gland cancer
prostate cancer
rhabdomyoma
rhabdomyosarcoma
thyroid cancer, medullary
uterine tumor (corpus and/or cervix)

Non-tumor features

lung cysts
pneumothorax, spontaneous

Comment

This condition is characterized by the presence of 3 types of benign skin tumors: fibrofolliculomas, trichodiscomas and acrochordons[1-4], although its has been questioned whether acrochordons truly belong to this hereditary disorder[5]. Trichoblastoma has been reported as well[15]. Spontaneous pneumothorax (fifty-fold increase in risk), cystic lung disease and multifocal renal cancer are the other hallmarks of Birt-Hogg-Dubé syndrome (BHD).[12,14]. Various histology has been observed in the renal tumors: oncocytoma, chromophobe carcinoma, clear cell as well tubulo or tubulo-papillary renal cell carcinomas. Most tumors have an oncocytic component, mixed histology is common.[10,11,13,14,16].

Benign and malignant adenomatous colon polyps have been reported in patients with this disorder and with what some consider to be a variant of Birt-Hogg-Dubé syndrome: Hornstein-Knickenberg syndrome, which is characterized by multiple perifollicular fibromas[6-9]. Other tumors have been reported in incidental cases: parotid gland oncocytoma, cutaneous melanoma, leiomyoma, leiomyosarcoma, dermatofibrosarcoma, head and neck squamous cell cancer, colon cancer, Hodgkin disease, uterine cancer (not specified), breast and prostate cancer[14], In one large family with BHD, medullary thyroid cancer was diagnosed in several relatives, 2 of them also presenting with the skin tumors. It may have been a coincidental co-segregation of familial medullary thyroid cancer and BHD.

Links

BHDsyndrome.org 24 9 2009

References

[1] Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol 1977; 113:1674-1677.
[2] Weintraub R, Pinkus H. Multiple fibrofolliculomas(Birt-Hogg-Dube) associated with a large connective tissue nevus. J Cutan Pathol 1977; 4:298-299.
[3] Bayrou O, Blanc F, Moulonguet I, Millet P, Garrel JB, Civatte J. Syndrome de Birt-Hogg-Dube. Fibrofolliculomes, trichodiscomes et acrochordons. Ann Dermatol Venereol 1990; 117:37-41.
[4] Cohen PR, Kurzrock R. Miscellaneous genodermatoses: Beckwith-Wiedemann syndrome, Birt- Hogg-Dube syndrome, familial atypical multiple mole melanoma syndrome, hereditary tylosis, incontinentia pigmenti, and supernumerary nipples. Dermatol Clin 1995; 13(1):211-229.
[5] De la Torre C, Ocampo C, Doval IG, Losada A, Cruces MJ. Acrochordons are not a component of the Birt-Hogg-Dube syndrome: does this syndrome exist? Case reports and review of the literature. Am J Dermatopathol 1999; 21(4):369-374.
[6] Hornstein OP, Knickenberg M. Perifollicular fibromatosis cutis with polyps of the colon _ a cutaneo-intestinal syndrome sui generis. Arch Dermatol Res 253, 161-175. 1975.
[7] Hornstein OP. Generalized dermal perifollicular fibromas with polyps of the colon. Hum Genet 33, 193-197. 1999.
[8] Simon Mjr, Hornstein OP, Haneke E. Perifollikulare fibromatose. Eine kutane paraneoplasie? Der Hautartz 1982; 33:481-483.
[9] McKenna DB, Barry-Walsh C, Leader M, Murphy GM. Multiple perifollicular fibromas. J Eur Ac Derm Venereol 1999; 12(3):234-237.
[10] Toro JR, Glenn G, Duray P, Darling T, Weirich G, Zbar B, Linehan M, Turner ML. Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia. Arch Dermatol 1999; 135(10):1195-1202.
[11] Leter EM, Koopmans AK, Gille JJ, van Os TA, Vittoz GG, David EF, Jaspars EH, Postmus PE, van Moorselaar RJ, Craanen ME, Starink TM, Menko FH. Birt-Hogg-Dubé syndrome: clinical and genetic studies of 20 families. The Journal of investigative dermatology 2008; 128(1):45-9.
[12] Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, Wei MH, Schmidt LS, Davis L, Zbar B, Choyke P, Steinberg SM, Nguyen DM, Linehan WM. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome. American journal of respiratory and critical care medicine 2007; 175(10):1044-53.
[13] Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. American journal of human genetics 2005; 76(6):1023-33.
[14] Toro JR, Wei MH, Glenn G, Weinreich M, Toure O, Vocke C, Turner ML, Merino M, Pinto P, Steinberg S, Schmidt L, Linehan WM. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube Syndrome: A new series of 50 families and a review of published reports. Journal of medical genetics 2008;45(6):321-31.
[15] Imada K, Dainichi T, Yokomizo A, Tsunoda T, Song YH, Nagasaki A, Sawamura D, Nishie W, Shimizu H, Fukagawa S, Urabe K, Furue M, Hashimoto T, Naito S. Birt-Hogg-Dubé syndrome with clear-cell and oncocytic renal tumour and trichoblastoma associated with a novel FLCN mutation. Br J Dermatol. 2009 Apr 16. [Epub ahead of print]
[16] Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER; European BHD Consortium. Birt-Hogg-Dubé syndrome: diagnosis and management. Lancet Oncol. 2009 Dec;10(12):1199-206.