Rare Germline Variants in the Adenomatous Polyposis Coli Gene Associated with Dental and Osseous Anomalies

Abstract

APC is a tumor suppressor gene that exerts its effect through the regulation of the Wnt signaling pathway. Loss of function mutations of the gene are associated with familial adenomatous polyposis (FAP). Early diagnosis in FAP patients is essential to prevent the development of colorectal cancer. Extraintestinal manifestations often precede the formation of the polyposis; therefore, these manifestations may serve as a clinical indicator for the condition. The aim of this study was to assess genotype–phenotype associations between the location of APC mutations and various extraintestinal features, mainly focusing on osseous and dental anomalies. Analyses of our cases and the mutations available in the literature with these manifestations revealed that mutations in the N-terminal region (amino acids 1–~1000) of the protein are more frequently associated with only osseous anomalies, whereas dental manifestations are more prevalent in mutations in the middle region (amino acids 1000–~2100). In addition, supernumerary teeth were found to be the most common dental feature. Since dental abnormalities often precede intestinal polyposis, dentists have a crucial role in the early identification of patients at risk.