Int. J. Oral Maxillofac. Surg. 2004; 33: 117–124 doi:10.1054/ijom.2003.0435, available online at http://www.sciencedirect.com Invited Review Paper Clinical Pathology Nevoid basal cell carcinoma syndrome: a review of the literature M. Manfredi, P. Vescovi, M. Bonanini, S. Porter: Nevoid basal cell carcinoma syndrome: a review of the literature. Int. J. Oral Maxillofac. Surg. 2004; 33: 117–124. 2003 International Association of Oral and Maxillofacial Surgeons. Publis hed by Elsevie r Ltd. All rights reserved. Abstract. The nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin–Goltz Syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The present report reviews current knowledge of this disorder that has profound releva nce to specia lists in Oral and Maxillo- Facial Surgery, Oral Medicine and Radiology. M. Manfredi 1,2 , P. Vescovi 1 , M. Bonanini 1 , S. Porter 2 1 Sezione di Odontostomatologia— Dipartimento Scienze Otorino-Odonto Oftalmologi che e Cerv ico-Faccial i, Universi ta ` degli Studi di Parma, Italy; 2 Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, UCL, London, UK Key words: basal, carcinoma, nevoid, oral, syndrome Accepted for publication 16 April 2003 The nev oid bas al cel l car cinoma syn - drome (NBCCS) was first report ed by Jarish in 1894 33 who described a patient with multiple basal cell carcin omas, sco- liosis and learning disability. Howell & Caro in 1959 32 were the first to associate the basal cell nevus with other cutaneous disorders and anomalies, while in 1960 Gorlin & Goltz 24 defined the condition as a syndrome comprising the principal triad of mult iple basal ce ll ne vi, jaw keratocys ts, and skelet al anomalies 32 . A spectrum of other neurological, oph- thalmic, endocrine, and genital manifes- tations 24,74,75 are now kn own to be variably associated with this triad 60,64 . Epidemiology and genetics The Ne vo id B as al Ce ll Carc ino ma Syndrome prevalence has been variously esti mated from 1 in 57 000 17 to 1 in 164 000 65 , bu t t he re is no w ge ne r al agreement that the prevalence is about 1 per 60 000 28 . NBCCS probably arises in all ethnic groups, but most reports have been of whites. Males and females are equally aff ected, the clinical features ofNBCCS aris ing in the first, second or third decad e 14,35 . This disorder has an autosomal dominant mod e of inherit- ance, but can arise spontaneously, or can have a variable phenot ypic pene tra- tion 7,24,26 . Indeed almost 60% of pat ients with NBCCS have no kno wn aff ected family members, 35 to 50% ofthese representing new mutations 27 . The causative gene of NBCCS is on chromo- some 9q (22.3-q31) and has no apparent heterogeneity 7,19 . This defect also occurs in rele van t spo radic tumour s such as basal cell carcin oma, medul loblas toma and trichoepithelioma 19,27 . The genet ic mecha nisms that under lie NBCCS have received considerable attention in recent years. The principal causative mutations occur in the human equiv alent of the Patched (PTCH) gene, this functioning as a tumour suppressor gene as well as having other roles 9,17,20 . In Drosophila the Patche d (PTC) gene fun ct io ns as a co mp o nent of the Hedgehog signalling pathway. Hedge- hog (HH) 34 is a diff usible protein that bi nd s t o, an d inhi bi ts PTC. In the absen ce of this HH-induced inhibitio n PTC ac ts to in hi bi t s mo o th en e d (SMO), an adjacent transmembrane pro- tei n. Whe n act ivat ed, SMO cau ses the activation of Cubitus interruptus (CI), a transcription factor that activates tran- sc ri pt ion of wi ngle ss , r ot a te d a nd decae ntapl egic, and repres ses transc rip- tion of HH 11 . The human equivalent ofth e Patc he d ge ne (PTCH) li ke wi se interact s with a hedgehog sig nalli ng system. In verte brates Sonic hedge hog (S HH) is the member of a family of hed gehog signal ling pro tei ns ess ent ial in dev e lo pm en t. Of r el e va nc e to NBCCS the Sonic Hedgehog signalling path way is e xp r es s ed d ur in g earl y murine tooth development and in vitro, the addition of exogenous SHH protein in to an d ad jace nt to ea r ly t oo t h ger ms res ult s in abn ormal epithe lium invagin ati on—hen ce demonstratin g th at the SHH/ PTCH syst em h as an es s en t ial role in od onto ge ne si s 30 . There is evidence that mutati ons in PTCH account for the development 0901-5027/04/020117+08 $30.00/0 2003 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
