A Family With Brooke-Spiegler Syndrome: Analysis Of The Clinical Features And Mutation Detection

Background Brooke-Spiegler syndrome(BSS, OMIM# 605041) is an autosomal dominantly inherited disease characterized by multiple skin appendage tumors, which usually begin to appear in the second or third decades, increasing in number and size throughout adult life. The expression and penetrance are variable. The predominating tumor can be a cylindroma, trichoepithelioma, and/or spiradenoma. Although cylindromas and spiradenomas are sweat gland tumors, trichoepitheliomas show hair follicle differentiation. Therefore, it has been postulated that BSS results from defects in the regulation of putative stem cells of the folliculo-sebaceous-apocrine unit(FSAU), giving rise to different skin appendage tumors. Two autosomal dominantly inherited genodermatoses, familial cylindromatosis (FC, OMIM# 132700), and multiple familial trichoepithelioma (MFT, OMIM# 601606), have been originally described as distinct entities. The gene for FC was mapped to chromosome 16q12-q13 by linkage analysis. The CYLD gene was discovered by positional cloning and germline mutations were identified in families with this disease. Loss of heterozygosity at the CYLD locus has been found in both inherited and sporadic tumors, implicating CYLD as a tumor suppressor gene. Subsequently, mutations in CYLD in patients with BSS phenotype were found. More recently, CYLD has been identified as the susceptibility gene for several families with MFT. These findings, taken together with the observations that features of BSS, FC, and MFT can occur in the same patient or in different patients within a single family, and that a single CYLD mutation can be associated with both cylindromas and trichoepitheliomas, suggest that these syndromes not only share a common genetic basis but represent phenotypic variation of the same disease. To date,...