Brooke-Spiegler Syndrome

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The Brooke-Spiegler syndrome ( Henry Ambrose Grundy Brooke , English dermatologist , Manchester , 1854-1919; Eduard Spiegler , Austrian chemist and dermatologist, Vienna , 1860-1908) is a rare autosomal dominant hereditary disease that is predisposed to Development of tumors of the skin or skin appendages ( dermal cylindromas , spiradenomas , trichoblastomas or basal cell carcinomas ). In addition, the affected patients also show an increased risk of developing salivary gland tumors such as basal cell adenomas or adenocarcinomas of the parotid gland or the small salivary glands.

Molecular pathology

It is based on a mutation of the CYLD tumor suppressor gene on chromosomes 16q12 – q13. CYLD intervenes in the NF-κB (Nuclear Factor Kappa B) signaling pathway and counteracts NF-κB activation. NF-κB, in turn, is an inducible transcription factor that plays a key role in inflammation , immune response and oncogenesis . NF-κB suppression leads, among other things, to severe defects in the early phase of the development of skin appendages such as hair follicles and sweat glands . The exact mechanism of the CYLD-dependent tumorigenesis is still unknown.

Individual evidence

  1. ↑ DV Kazakov, R. Soukup, P. Mukensnabl, L. Boudova, M. Michal: Brooke-Spiegler syndrome: report of a case with combined lesions containing cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation. In: Am J Dermatopathol. 2005 Feb; 27 (1), pp. 27-33. PMID 15677973
  2. ^ S. Bowen, M. Gill, DA Lee, G. Fisher, RG Geronemus, ME Vazquez, JT Celebi: Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation . In: J Invest Dermatol. 2005 May; 124 (5), pp. 919-920. PMID 15854031
  3. ↑ GR Bignell, W. Warren, S. Seal, M. Takahashi, E. Rapley, R. Barfoot, H. Green, C. Brown, PJ Biggs, SR Lakhani, C. Jones, J. Hansen, E. Blair, B. Hofmann, R. Siebert, G. Turner, DG Evans, C. Schrander-Stumpel, FA Beemer, A. van Den Ouweland, D. Halley, B. Delpech, MG Cleveland, I. Leigh, J. Leisti, S. Rasmussen: Identification of the familial cylindromatosis tumor-suppressor gene. In: Nat Genet . 2000 Jun; 25 (2), pp. 160-165. PMID 10835629
  4. ^ DA Lee, ME Grossman, P. Schneiderman, JT Celebi: Genetics of skin appendage neoplasms and related syndromes. In: J Med Genet. 2005 Nov; 42 (11), pp. 811-819. PMID 16272260 .