title: Brooke-Spiegler Syndrome and Phenotypic Variants: An Update.
abstract: Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms most commonly spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. Multiple familial trichoepithelioma (MFT) is a phenotypic variant of the disease characterized by the development of numerous trichoepitheliomas (cribriform trichoblastoma) only. Malignant tumors arise in association with preexisting benign cutaneous neoplasms in about 5-10% of the patients . Apart from the skin, major and minor salivary glands have been rarely involved in BSS patients. Extremely rare is the occurrence of breast tumors (cylindroma). The gene implicated in the pathogenesis of the disease is the CYLD gene, a tumor suppressor gene located on chromosome 16q12-q13. Germline CYLD mutations are detected in about 80-85% of patients with the classical BSS phenotype and in about 40-50% of the individuals with the MFT phenotype using a PCR based approach with analysis of exonic sequences and exon-intron junctions of the CYLD gene. There appears to be no genotype-phenotype correlations with respect to the severity of the disease, the possibility of malignant transformation, and development of extracutaneous lesions.
authors.affiliation: Department of Pathology, Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic. kazakov@medima.cz.|Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Alej Svobody 80, 304 60, Pilsen, Czech Republic. kazakov@medima.cz.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
mesh_terms: D000074749:Deubiquitinating Enzyme CYLD; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: Brooke-Spiegler syndrome; CYLD gene; Cylindroma; Spiradenoma; Trichoepithelioma