Background: Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin-Goltz syndrome) presents various symptoms and can disfigure patients. The estimated prevalence is around 1:100,000. Objective: To systematically investigate the clinical manifestations of NBCCS patients of the Zurich register and compare them with those described in 4 epidemiological studies performed in other countries. Methods: We analyzed patient characteristics and clinical manifestations in a register of 30 NBCCS patients in Zurich, Switzerland. We compared our findings to the results of 4 epidemiological studies performed in America, Australia, Japan and the UK. Results: We obtained information concerning basal cell carcinomas (BCCs) and jaw cysts from 28 patients out of our population of 30 NBCCS patients. The mean age at onset of the first BCC was 24 years, and the mean age at diagnosis of the first jaw cyst was 15.6 years. The average number of jaw cysts was 8.4; the average number of BCCs was 207. 72.5% of the examined BCCs showed a nodular histology, but we also found scirrhous and superficial types. Conclusion: The disease burden associated with NBCCS diagnosed in Swiss patients is significant and comparable to that of other countries. Regular skin examination and oromaxillary examinations should be performed early in diagnosis, and patients should undergo early UV protection. Nodular BCC is the most common BCC subtype in this patient population.

Keywords:
Gorlin-Goltz syndrome, Basal cell carcinoma, Jaw cysts, Nevoid basal cell carcinoma syndrome
1.
Gorlin RJ, Goltz RW: Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 1960;262:908-912.
2.
Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, Lalloo F: Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327-332.
3.
Lo Muzio L, Nocini PF, Savoia A, Consolo U, Procaccini M, Zelante L, Pannone G, Bucci P, Dolci M, Bambini F, Solda P, Favia G: Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals. Clin Genet 1999;55:34-40.
5.
Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH: Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 2012;366:2180-2188.
6.
Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G: Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the patched protein, and no genotype-phenotype correlations are evident. Am J Hum Genet 1997;60:21-26.
7.
Smith MJ, Beetz C, Williams SG, Bhaskar SS, O'Sullivan J, Anderson B, Daly SB, Urquhart JE, Bholah Z, Oudit D, Cheesman E, Kelsey A, McCabe MG, Newman WG, Evans DG: Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J Clin Oncol 2014;32:4155-4161.
8.
Wilding A, Ingham SL, Lalloo F, Clancy T, Huson SM, Moran A, Evans DG: Life expectancy in hereditary cancer predisposing diseases: an observational study. J Med Genet 2012;49:264-269.
9.
Bree AF, Shah MR; BCNS Colloquium Group: Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A 2011;155A:2091-2097.
10.
Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, Bale AE, Bale SJ: Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299-308.
11.
Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA: Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet 1993;30:460-464.
12.
Shanley S, Ratcliffe J, Hockey A, Haan E, Oley C, Ravine D, Martin N, Wicking C, Chenevix-Trench G: Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. Am J Med Genet 1994;50:282-290.
13.
Endo M, Fujii K, Sugita K, Saito K, Kohno Y, Miyashita T: Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing the low frequency of basal cell carcinoma. Am J Med Genet A 2012;158A:351-357.
14.
Wright AT, Magnaldo T, Sontag RL, Anderson LN, Sadler NC, Piehowski PD, Gache Y, Weber TJ: Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis. Mol Carcinog 2015;54:473-484.
15.
Mallinson EK, Newton KF, Bowen J, Lalloo F, Clancy T, Hill J, Evans DG: The impact of screening and genetic registration on mortality and colorectal cancer incidence in familial adenomatous polyposis. Gut 2010;59:1378-1382.
16.
Wrone DA, Swetter SM, Egbert BM, Smoller BR, Khavari PA: Increased proportion of aggressive-growth basal cell carcinoma in the Veterans Affairs population of Palo Alto, California. J Am Acad Dermatol 1996;35:907-910.
17.
Scrivener Y, Grosshans E, Cribier B: Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. Br J Dermatol 2002;147:41-47.
18.
Dreier J, Cheng PF, Bogdan Alleman I, Gugger A, Hafner J, Tschopp A, Goldinger SM, Levesque MP, Dummer R: Basal cell carcinomas in a tertiary referral centre: a systematic analysis. Br J Dermatol 2014;171:1066-1072.
19.
Bronoosh P, Shakibafar AR, Houshyar M, Nafarzade S: Imaging findings in a case of Gorlin-Goltz syndrome: a survey using advanced modalities. Imaging Sci Dent 2011;41:171-175.
20.
Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC, de Sauvage FJ, Low JA: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164-1172.
21.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A: Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-2179.
22.
Dreier J, Dummer R, Felderer L, Nägeli M, Gobbi S, Kunstfeld R: Emerging drugs and combination strategies for basal cell carcinoma. Expert Opin Emerg Drugs 2014;19:353-365.
23.
Basset-Seguin N, Hauschild A, Grob JJ, Kunstfeld R, Dréno B, Mortier L, Ascierto PA, Licitra L, Dutriaux C, Thomas L, Jouary T, Meyer N, Guillot B, Dummer R, Fife K, Ernst DS, Williams S, Fittipaldo A, Xynos I, Hansson J: Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol 2015;16:729-736.
24.
Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, Herd RM, Kudchadkar R, Trefzer U, Gogov S, Pallaud C, Yi T, Mone M, Kaatz M, Loquai C, Stratigos AJ, Schulze HJ, Plummer R, Chang AL, Cornélis F, Lear JT, Sellami D, Dummer R: Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015;16:716-728.
25.
Ally MS, Tang JY, Joseph T, Thompson B, Lindgren J, Raphael MA, Ulerio G, Chanana AM, Mackay-Wiggan JM, Bickers DR, Epstein EH: The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome. JAMA Dermatol 2014;150:542-545.
26.
Otsuka A, Dreier J, Cheng PF, Nägeli M, Lehmann H, Felderer L, Frew IJ, Matsushita S, Levesque MP, Dummer R: Hedgehog pathway inhibitors promote adaptive immune responses in basal cell carcinoma. Clin Cancer Res 2015;21:1289-1297.
27.
Brugières L, Remenieras A, Pierron G, Varlet P, Forget S, Byrde V, Bombled J, Puget S, Caron O, Dufour C, Delattre O, Bressac-de Paillerets B, Grill J: High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J Clin Oncol 2012;30:2087-2093.
28.
Archer TC, Weeraratne SD, Pomeroy SL: Hedgehog-GLI pathway in medulloblastoma. J Clin Oncol 2012;30:2154-2156.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.