Oligodontia-Colorectal Cancer Syndrome

A number sign (#) is used with this entry because of evidence that tooth agenesis-colorectal cancer syndrome is caused by heterozygous mutation in the AXIN2 gene (604025) on chromosome 17q24.

Clinical Features

Lammi et al. (2004) described a Finnish family in which severe permanent tooth agenesis (oligodontia) and colorectal neoplasia segregated with dominant inheritance. Eleven members of the family lacked at least 8 permanent teeth; 2 of them developed only 3 permanent teeth. Colorectal cancer or precancerous lesions of variable types were found in 8 of the patients with oligodontia.

Molecular Genetics

Using positional cloning, Lammi et al. (2004) demonstrated that the oligodontia and predisposition to cancer in this family were caused by an arg656-to-ter mutation in the AXIN2 gene (R656X; 604025.0003). In addition, they identified a de novo frameshift mutation in AXIN2 in an unrelated 13-year-old boy with severe tooth agenesis who may have been too young to manifest colorectal neoplasia.

In 3 probands with mild oligodontia, who were missing 7 to 10 teeth each, Bergendal et al. (2011) identified heterozygosity for 1 frameshift and 2 missense mutations in the AXIN2 gene, respectively. The patients were not clinically ascertained, but reported no other ectodermal features or colorectal cancer in themselves or other family members. One of the patients, a 17-year-old girl who was missing 8 teeth and whose mother was missing 9 teeth, carried the same 1994dupG mutation that had been previously reported in a 13-year-old boy with severe tooth agenesis by Lammi et al. (2004).

In a 3-generation family segregating autosomal dominant oligodontia variably associated with colon or gastric polyps, early-onset colorectal and/or breast cancer, and sparse hair and eyebrows, Marvin et al. (2011) identified a heterozygous nonsense mutation in the AXIN2 gene (W663X; 604025.0004). The proband, her mother, 2 maternal aunts, and her deceased maternal grandmother all had oligodontia. Of the 5 affected individuals, 4 had sparse hair and eyebrows; 3 had colon polyps and/or colon cancer, and 1 also had breast cancer diagnosed at age 44 years. Only the maternal grandmother, who died at age 97, had no known history of polyps or cancer.