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Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant neurocutaneous disease characterized by developmental anomalies such as palmar pits and rib anomaly, and tumorigenesis such as medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a mutation of PTCH1, a human homologue of Drosophila patched, including frameshift, missense, or nonsense mutations. Genotype-phenotype correlation has not been established. PTCH1 is a member of hedgehog signaling, which is a highly conserved pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as PTCH1. Given that hedgehog signaling regulates cell growth and development, disorder of this pathway gives rise to not only developmental anomalies but also diverse tumors such as those seen in Gorlin syndrome. We recently reported, for the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the frequency was 1/235 800 in the Japanese population, and that the frequency of basal cell carcinomas was significantly lower in Japan than in the USA and Europe, suggesting that ethnicity and genetic background contribute to these differences. Given that many clinical trials using newly discovered molecular inhibitors are still ongoing, these agents should become the new therapeutic options for hedgehog pathway-dependent tumors in patients with or without Gorlin syndrome. [ABSTRACT FROM AUTHOR]

Abstract: In the present report, we review the clinical features and biophysiological roles, including gene expression, of nevoid basal cell carcinoma syndrome (NBCCS) in Japanese cases. The frequency of clinical findings of Japanese cases (n =186) was reported in NBCCS including keratocystic odontogenic tumors (KOTs). The syndromes resulted from mutation in the patched (PTCH1) gene in both neoplastic lesion basal cell carcinoma (BCCs) and KOTs. BCCs originate from hair follicles and express Gli gene; KOTs, classically known as odontogenic keratocysts, originate from odontogenic epithelial rest cells and considerable variation in the recurrence rate after surgery. PTCH1 gene alteration may have significant roles in the pathogenesis of NBCCS and sporadic KOTs. However, their histogenetic origin was found to differ: basal cell carcinoma in the skin originated from hair follicle cells and KOTs originated from odontogenic epithelial rest cells in the jaw. [Copyright &y& Elsevier]

The article discusses the biological principles on the detection of mutation-negative cases with nevoid basal cell carcinoma syndrome or Gorlin syndrome in Japan. It notes that the syndrome is an autosomal dominant neurocutaneous disorder that is characterized by growth abnormalities of human body and skeleton as well as sensitivity to radiation and an increased incidence of cancers. It suggests the investigation of the possibility of the gene deletion in point mutation-negative cases.

Objectives. We rarely find multiple cystic lesions in the jaw in panoramic radiographs. Most reports of multiple cystic lesions have described keratocystic odontogenic tumors (KOTs) in patients with basal cell nevus syndrome. In this study, we performed radiographic and clinical examinations of patients with multiple cystic jaw lesions found during their first visit to our department to determine the proportion of basal cell nevus syndrome among multiple cystic lesions. Methods. Patients who had a panoramic radiograph taken at Okayama University Hospital between 1993 and 2000 were examined. Twenty-three patients with multiple cystic jaw lesions on a first panoramic radiography examination were entered into this study. Results. Of the 23 patients, 12 (52.2%) were diagnosed with basal cell nevus syndrome and 11 (47.8%) were not. Of the 14 patients with multiple KOTs, 12 (85.7%) were diagnosed as having basal cell nevus syndrome. Of the nine remaining patients with multiple cystic jaw lesions, only seven had multiple dentigerous cysts and two had multiple simple bone cysts. Cleft palate was observed in four of the 12 patients (33.3%) with basal cell nevus syndrome. Conclusion. Diagnosing basal cell nevus syndrome based on multiple cystic jaw lesions carries a high risk of misdiagnosis. A strong possibility exists that patients with multiple jaw KOTs have basal cell nevus syndrome. Furthermore, cleft palate should be considered an important oral finding in basal cell nevus syndrome because its occurrence was relatively frequent in our study. [ABSTRACT FROM AUTHOR]