Gorlin syndrome (nevoid basal cell carcinoma syndrome): Update and literature review

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 1/235800 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.