Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene

The AXIN2 gene, like APC, plays a role in the Wnt signalling pathway involved in colorectal tumour formation. Heterozygous mutations in AXIN2 have been shown to cause ectodermal dysplasia (including tooth agenesis, or more specifically, oligodontia), and, in some carriers, colorectal cancer and/or adenomatous polyposis develops. There is a paucity of published AXIN2 families making genotype-phenotype (polyposis, colorectal cancer and oligodontia) correlations challenging. In this case report we describe a family with c.1972delA, p.Ser658Alafs*31 nonsense variant in AXIN2 where the three confirmed carriers presented with both oligodontia and colorectal adenomatous polyposis; mean number of teeth missing in carriers was 16.5 (range 11–22) and mean number of polyps in carriers was 49 (range 5->100, polyps were predominantly adenomatous). This highlights the importance of confirming phenotypic information in familial polyposis, to guide appropriate genetic investigations, as well as providing additional phenotypic and penetrance data to aid in clinical risk management recommendations. Our experience supports the inclusion of AXIN2 on panels for testing of patients with polyposis.