Skeletal and cranio-facial signs in Gorlin syndrome from ancient Egypt to the modern age: sphenoid asymmetry in a patient with a novel PTCH1 mutation

Gorlin-Goltz syndrome is an autosomal dominant disorder linked to PTCH1 mutation, identified by a collection of clinical and radiologic signs. NBCCS clinical behavior is basically benign, since the pathognomonic PTCH1 mutation has been preserved during the centuries as it's witnessed from the presence of criteria for Gorlin syndrome in Egyptian mummies. We describe here the peculiar case of a family in which father and son fulfilled clear cut diagnostic criteria for Gorlin-Goltz syndrome including multiple basal cell carcinomas, keratocystic odontogenic tumours, segregation of the clinical phenotype in multiple family members, atypical skeletal anomalies and a novel PTCH1 germline mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D and helical CT scan were: macrocephaly, positional plagiocephaly, skull base asymmetry, mandibular prognathism, mandibular condylar deformation with hyperplasia of the coronoid process, bifidity of multiple ribs and giant multilocular odontogenic jaw cysts. Extensive multilamellar calcifications were found in falx cerebri, tentorium, falx cerebelli and in the apical segment of the atlanto-occipital ligament. Thoracic anomalies included bifid ribs and sacrum acutum. Interestingly, volume-CT scan with multiplanar and 3D reconstruction identified a significant asymmetry of sphenoid wings with dysmorphic features. Abnormalities of the sphenoid bone are not very common, and consist of differently aggressive entities: some of them are typical of the pediatric age in few hereditary and congenital disorders. The application of new criteria (i.e. peculiar calcifications of ligaments and sphenoid asymmetry) to a wider case series can lead to the early diagnosis of Gorlin syndrome, especially in pediatric patients, when the full phenotype is not yet expressed. The inclusion of bifid ribs as a novel major criteria and the recognition of peculiar cranial anomalies such as sphenoid asymmetry, well detected at volume CT reconstruction, might be useful for the recognition and characterization of misdiagnosed cases.