Mosaicism for a variant in PTCH1 causing nevoid basal cell carcinoma syndrome

This case report details the diagnostic process in a young man with mosaic nevoid basal cell carcinoma syndrome (NBCCS). In his mid-teens, he was first diagnosed with basal cell carcinoma (BCC). By late adolescence, he presented with mild NBCCS-like features alongside an identified odontogenic keratocyst. Although meeting diagnostic NBCCS criteria, no pathogenic variants were detected in DNA from blood. In DNA from the BCC and the odontogenic keratocyst, heterozygosity for the likely pathogenic variant in PTCH1: c.2917C>T p.(Gln973*) was identified, alongside additional PTCH1 variants specific to each tissue. A hereditary predisposition should be suspected in cancer patients diagnosed at an unusually young age for their tumour type and/or in individuals presenting with dysmorphic features. In cases where the two-hit mechanism is involved, and with no pathogenic variant detected in blood, sequencing should be repeated in two or more samples from affected tissue.