Genetic characteristics and extracolonic phenotypic manifestations in patients with familiar adenomatous polyposis

Familial adenomatous polyposis (FAP) is a hereditary disease caused by mutations in the APC gene, which is also associated with extracolonic manifestations. The objective was to characterize the extracolonic manifestations in a cohort of patients with classic FAP and the possible genotype-phenotype association.

The study design was observational and descriptive. Demographic, clinical, and genetic variables were collected based on the type of mutation (frameshift, nonsense, splicing, rearrangement, and others).

We included 45 patients with FAP (mean age 47years, range 21-78; 51% female), belonging to 21 families, with a median of 2 (range 0-6) manifestations per patient. Eighty percent (n=36) had upper digestive tract involvement, with duodenal adenomas (73%), fundic gland polyposis (56%), and ampullary adenoma (36%) being the most frequent findings. The most common extraintestinal manifestations were desmoid tumors (16%) and papillary thyroid carcinoma (13%). Thirty eight percent of the patients presented an aggressive phenotype (SpigelmanIII-IV, high-grade dysplasia, invasive neoplasia, desmoid tumor, and papillary thyroid carcinoma). The most common genetic mutations were frameshift (56%), nonsense (26%), and splicing (16%), primarily located in exon15 (50%). No significant correlation was found between the type of genetic mutation and the severity or location of phenotypic manifestations.

One-third of patients with FAP present an aggressive phenotype, without a demonstrated correlation between the type of genetic alteration and the phenotypic manifestations.