Birt-hogg-dubé syndromeD23.-

Hereditary, familial or sporadic, very rare syndrome characterized by multiple neoplasms originating from the connective tissue of the hair shaft and diseases of various extracutaneous organs, especially the lungs and kidneys. lungs and kidneys.

The syndrome is secondary to a germline mutation in the folliculin(FLCN) gene, which is located on chromosome 17p11.2 and encodes the folliculin protein (Baba M et al. 2006). A number of mutations have been detected, including deletions, substitutions, and duplications, which are thought to lead to truncation of the protein and consequent loss of function.

Folliculin is expressed in a number of normal tissues, including skin, lung, and kidney, although its exact function as a protein remains unknown. Recent evidence suggests that folliculin functions as a tumor suppressor via an interaction with the mTOR energy processing pathway, and its absence contributes to the development of BHDS-associated renal tumors. There may be subtypes of BHDS, as lung cysts are the predominant feature in some families and skin and renal manifestations are less common. In addition, mutations may be specific to certain ethnicities, as Japanese and Caucasian patients have been found to have different mutation distributions and unique alterations

Involvements of the VHL and tyrosinase kinase domains of the Met proto-oncogene family and the PTCH, PTEN, and CTNNB1 genes have also been described.

• Integument: Multiple, skin-colored, flesh-colored or waxy shiny, relatively coarse, 2-5 mm in size, hemispherical asymptomatic papules, often oral. These are usually combinations of histologically different structures, e.g.
  • Fibrofolliculoma
  • trichodiscoma (tumors of the hair disc)
  • Fibroma molle or perifollicular fibroma (see also hair follicle tumor)
  • Lipoma
  • Angiolipoma
  • Basal cell carcinoma
  • Connective tissue nevus
  • Cutaneous, focal multiple mucinosis
• Extracutaneous manifestations:
  • Colon: multiple colonic adenomas with a high risk of degeneration to colorectal carcinoma.
  • Genitourinary tract: prostate carcinoma, renal cysts, renal angiolipomas, hyperuricemia.
  • Lung: emphysema, bronchiectasis, lung cysts, hamartomas of the lung.
  • Eyes: retinopathies, chorioretinopathies, glaucoma.
  • Endocrine system: thyroid carcinoma, hypothyroidism, parathyroid adenoma, diabetes mellitus.
  • Other: osteomas, hypertension, hepatic hemangiomas, uterine fibroids, facial nerve palsy, deafness, aplasia of anterior communicating artery.

Oral acanthosis nigricans

Goltz-Gorlin syndrome

Cowden syndrome

Wegener's granulomatosis

Reticulohistiocytosis

S.u. fibrofolliculoma, hair follicle tumor, trichodiscoma, fibroma molle; mucinosis cutaneous focal multiple

Regular colonoscopic screening examinations are urgently recommended (see also www.familienhilfe-polyposis.de).

1. Baba M et al. (2006) Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A 103:15552-15527.
2. Birt AR, Hogg GR, Dube WJ (1977) Hereditary multiple fibrofilliculomas with trichodiscomas and acrochordons. Arch Dermatol 113: 1674-1677.
3. Bournier R et al (1925) Fibromes sous-cutanes peripilaires multiples du cou. Bull Soc Fr Dermatol Syph 32: 242-243.
4. Bruce H et al (2009) Cutaneous manifestations of internal malignancy. Cancer J Clin 59: 73-98
5. Burgdorf WHC et al (1988) Carcinoma-associated genodermatoses. Dermatologist 39: 413-418
6. Frantzen B et al (2001) Hornstein-Knickenberg and Birt-Hogg-Dube syndrome. Report of a case with spontaneous pneumothorax and aplasia of the left internal carotid artery. Dermatologist 52: 1016-1020
7. Gambichler T et al (2000) Treatment of Birt-Hogg-Dube syndrome with erbium:YAG laser. J Am Acad Dermatol 43: 856-858
8. Hornstein OP, Knickenberg M (1975) Perifollicular fibromatosis cutis with polyps of the colon- a cutaneo-intestinal syndrome sui generis. Arch Derm Res 253: 161-175
9. Lindor NM et al (2001) Birt-Hogg-Dube syndrome: an autosomal dominant disorder with predisposition to cancers of the kidney, fibrofolliculomas, and focal cutaneous mucinosis. Int J Dermatol 40: 653-656
10. Nickerson ML et al (2002) Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2: 157-164
11. Okimoto K et al (2004) A germ-line insertion in the Birt-Hogg-Dube (BHD) gene gives rise to the Nihon rat model of inherited renal cancer. Proc Natl Acad Sci U S A 101: 2023-2027.
12. Schulz T, Hartschuh W (2000) Characteristics of the Birt-Hogg-Dube/Hornstein-Knickenberg syndrome. Am J Dermatopathol 22: 293-294.
13. Schulz T, Hartschuh W (1999) Birt-Hogg-Dube syndrome and Hornstein-Knickenberg syndrome are the same. Different sectioning technique as the cause of different histology. J Cutan Pathol 26: 55-61
14. Vincent A et al (2003) Birt-Hogg-Dube syndrome: a review of the literature and the differential diagnosis of firm facial papules. J Am Acad Dermatol 49: 698-705.
15. Vincent A et al (2003) Birt-Hogg-Dube syndrome: two patients with neural tissue tumors. J Am Acad Dermatol 49: 717-719.
16. Warren MB et al (2004) Expression of Birt-Hogg-Dube gene mRNA in normal and neoplastic human tissues. Mod Pathol 17: 998-1011