3 in the area of the PTCH (Protein patched homolog) gene, a homolog of the Drosophila patched Olaparib side effects (PTC) gene, which encodes a transmembrane receptor protein (6). This protein binds a soluble hedgehog (Hh) family factor, thus activating the Smo (smoothened) receptor, that unblocks the transcription of various growth factors. The PTCH gene is thus an oncosuppressor forming part of the Sonic Hedgehog Homolog (Shh) signaling pathway and is crucial in embryonal development, the control of cell division and the growth of tumors (7). Mutations of this gene have been found in 50% of NBCCS patients (8). The relative rarity and phenotypic variability of NBCCS mean that its diagnosis is often delayed. The coexistence of basal cell carcinomas and jaw keratocysts are practically pathognomonic.

The pathogenesis of BCC is thought to involve a greater sensitivity to ultraviolet sunlight, i.e. inefficacy of the mechanisms that repair UV-induced DNA damage. However, this theory is not shared by all authors, as BCCs also appear in areas that have not been exposed to sunlight. In any case, NBCCS patients, especially children, undergoing radiotherapy for other cancers have been shown to be at an increased risk of radiation-induced BCCs (9). Jaw keratocysts, characterized by a thin surrounding layer of epithelial cells, are found in 50% of NBCCS patients (10). These cysts tend to recur locally after removal in 6�C60% of cases. It should thus be carefully considered if surgery is really indicated, taking into account the possibility of intensive clinical and instrumental monitoring alone (11).

There are numerous other possible signs of NBCCS (12). These include: palmar and plantar ulcers, appearing as shallow pits, caused by the partial or total absence of the corneal layer. Rarely, these may also appear along the sides of the hands and the fingers, and sometimes even on the tongue; spina bifida, often misdiagnosed or an incidental finding (1�C3, 12); medulloblastoma, which, especially in patients under the age of five years, may be epiphenomenal to NBCCS (13, 14); cardiac tumors, including fibromas and ventricular histiocytomas, that are often congenital and, if they cannot be enucleated, an indication for heart transplant (15); ameloblastoma, although this is rare, with only four cases reported in the literature (16, 17). As reported by Kimonis et al.

(12), the diagnosis of NBCCS requires the coexistence of at least two major criteria or one major and two minor criteria from those listed in Table 1. Table 1 DIAGNOSTIC CRITERIA FOR NBCCS – FROM KIMONIS VE, Batimastat ET AL. (11). Conclusions The difficulty in diagnosing NBCCS is justified by its rarity and phenotypic variability. Diagnosis is often delayed, especially in less severe forms, such as in our case. Once diagnosis has been made, family screening, including genetic testing, is indicated. For doubtful lesions a biopsy can be performed (18).