document: brook - spiegler syndrome ( bss ) is a rare genodermatosis characterized by the progressive formation of adnexal skin tumors in the scalp and face , mainly trichoepiteliomas , cylindromas and spiradenomas . 
   it is due to mutations in the tumor suppressor gene cyld ( cylindromatosis gene ) on chromosome 16q12q13 . around 93 mutations 
   the study of cyld gene in patients and their relatives can provide the molecular diagnosis and appropriate genetic counselling . 
   there is a low risk of malignancy and patients require long - term follow - up . 
   brooke  spiegler syndrome ( bss ) is a rare genodermatosis due to mutations in the tumor suppressor gene cylindromatosis ( cyld gene ) on chromosome 16q12q13 . 
   there is a low risk of malignancy and patients require long - term follow - up . 
   a 71-year - old woman was evaluated due to the progressive development of asymptomatic lesions in her head during the last 4 years . 
   the physical examination showed multiple rounded skin - colored or erythematous papules , 28 mm in diameter , located in scalp and forehead [ figure 1 ] . 
   we performed several excisional biopsies and the histopathological diagnosis was spiradenoma in all of the lesions , except for one cylindroma . 
   multiple rounded skin - colored or erythematous papules in scalp and forehead , compatible with spiradenomas and cylindromas regarding her family history , she referred the presence of lesions at the scalp and forehead in her mother , her mother 's brother , and two of her three daughters , some of them very similar to our patient s . 
   next , we performed a physical examination of her two affected daughters showing multiple papules and nodules of 13 cm , some of them painful [ figures 2 and 3 ] . 
   once all the information was collected , we elaborated the family pedigree , which suggested an autosomal dominant inheritance pattern of the disease [ figure 4a ] . above : rounded pink nodule with superficial telangiectasias at the scalp of one of the patient 's daughters . 
   below : multiple skin - colored or yellowish millimetric papules at the forehead and periocular area , suggesting multiple trichoepitheliomas multiple firm pink nodules of variable size in scalp of the second daughter ( a ) family pedigree . 
   ( b ) exon 8-cylindromatosis gene sequencing that shows ( a ) heterozygous mutation c. 1628_1629delct in our patient and her two affected daughters . 
   ( b ) wild - type genotype in the unaffected daughter suspecting a genetic syndrome , we requested the study of the cyld gene in our patient and her two affected offsprings . 
   the exon 8 sequencing of the cyld gene revealed the heterozygous mutation c. 1628_1629delct [ figure 4b ] . 
   it consists of a two base - pair deletion that originates a new frameshift , the first codon is now the stop codon p. ser543xfs*1 . 
   therefore , to complete the familiar study , we performed the genetic test on our patient 's daughter presenting no signs or symptoms suggesting bss . 
   the result was negative , showing the wild - type genotype [ figure 4b ] . 
   her 11 and 5-year - old children did not present any clinical data either . finally , we offered genetic counseling to her first - grade relatives . 
   we provided concise information about the main characteristics of sbs and the 50% probability of the descendants to develop this syndrome , due to its autosomal dominant inheritance . 
   it is characterized by the progressive development of adnexal skin tumors in scalp and face . 
   clinical manifestations start since puberty and its incidence is higher in females without distinction of race . 
   bss has also been associated with increased risk of salivary glands neoplasms and other tumors although with very little evidence . 
   cylindromas appear at the scalp reaching a considerable size , often forming the  turban tumor  . 
   spiradenomas are also multiple and appear in extremities , trunk and less frequently in the scalp ( this is a rare location of single sporadic spiradenomas ) . 
   recent studies demonstrate a common apocrine origin of spiradenomas and cylindromas , with an expression of hair follicle stem cells specific markers , mainly cd200 and cytokeratin . 
   thus , we prefer to avoid the adjective  eccrine  traditionally applied to spiradenomas . 
   this syndrome is due to mutations in the tumor suppressor gene cyld localized on chromosome 16q12q13 . 
   it is a tumor suppressor gene that codifies a protein of the deubiquitinating enzymes family . 
   it negatively regulates activation of factors such as nuclear factor - kappa - b , jnk , and wnt , involved in inflammation and cellular division . 
   the loss of deubiquitinating activity of cyld correlates with tumorigenesis ( apoptosis resistance , uncontrolled cell division ) . 
   germ - line mutations predispose to the disease , and sometimes , a second acquired somatic mutation determines the final phenotype . around 93 different mutations 
   its phenotypic expression has been found so far . the genetic study in our case revealed the existence of the heterozygotic mutation c. 1628_1629delct . 
   there is only one report of this mutation in 2008 found in a family with multiple trichoepitheliomas ; therefore , our case confirm the association of this genetic mutation with bss . 
   two entities have been recognized as phenotypic variations of bss ( mim#605041 ) due to mutations in the cyld gene . 
   multiple familial trichoepithelioma , also known as trichoepithelioma adenoides cystica ( mim#601606 ) , presents with numerous trichoepitheliomas since puberty predominantly located in the face . in familial cyld ( mim#132700 ) 
   , multiple cylindromas appear in face and scalp of the patients . on the other hand , 
   there have been described some cases of multiple familial spiradenomas , predominantly located in the scalp . 
   no genetic study was performed in these cases ; therefore , it could not be confirmed the existence of brss or one phenotypic variation . 
   alarm signs are ulceration , bleeding , fast growth , blue nodules , or pain . 
   malignant spiradenoma is a very aggressive neoplasm with a risk of metastasis around 50% and a mortality of 39% if left untreated . 
   we present a new case of bss in a family due to the heterozygous cyld mutation c. 1628_1629delct . 
   particularities of this case were the late onset in our patient and the relatively low number of cylindromas and trichoepitheliomas found in comparison with the cases found in the literature . 
   thus , our case may support the hypothesis about the influence of the concrete germline mutation and the variable presence of a somatic mutation in the development of the final phenotype . 
   for this reason , it is imperative to perform a correct diagnosis and periodic follow - up of the patients . 
   in addition , the genetic study should be considered individually with the possibility of genetic counseling to the family members . 
   the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) 
   has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . 
   the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . 
   we describe a new case of bss due to the rare heterozygous cyld gene mutation c.1628_1629delct in three women of the same family . 
   the particularities of the clinical manifestations ( late onset , relatively low number of tumors ) may support the hypothesis about the relationship between the germline mutation , variable presence of somatic mutation and the final phenotype . 
   the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) 
   has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . 
   the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . 
   we describe a new case of bss due to the rare heterozygous cyld gene mutation c.1628_1629delct in three women of the same family . 
   the particularities of the clinical manifestations ( late onset , relatively low number of tumors ) may support the hypothesis about the relationship between the germline mutation , variable presence of somatic mutation and the final phenotype . 
   the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) 
   has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . 
   the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . 
    
   we describe a new case of bss due to the rare heterozygous cyld gene mutation c.1628_1629delct in three women of the same family . 
   the particularities of the clinical manifestations ( late onset , relatively low number of tumors ) may support the hypothesis about the relationship between the germline mutation , variable presence of somatic mutation and the final phenotype .
summary: brooke  spiegler syndrome ( bss ) is a rare genodermatosis characterized by the progressive formation of adnexal skin tumors in the scalp and face , mainly trichoepitheliomas , cylindromas , and spiradenomas . 
   it has also been associated with salivary glands neoplasms . 
   it is due to mutations in the tumor suppressor gene cylindromatosis ( cyld gene ) localized on chromosome 16q12q13 . around 93 mutations 
   have been described . 
   the study of cyld gene in patients and their relatives is of vital importance to establish the molecular diagnosis and offer appropriate genetic counseling . 
   there is a low risk of malignancy and patients require long - term follow - up . a case of bss in a family 
   is described . 
   the existence of the genetic mutation at the cyld gene c. 1628_1629delct in three of the women affected was demonstrated . 
   this mutation has only been described once in a previous study .