Attenuated familial adenomatous polyposis (AFAP) in a patient associated with a novel mutation in APC

Correspondence to Dr Vivek Sant; [email protected]

Background

Familial adenomatous polyposis (FAP) is an autosomal, dominant, inherited syndrome associated with mutation in the adenomatous polyposis coli (APC) gene, with resultant clinical phenotype of numerous adenomatous colonic polyps and near-certain eventual progression to colon cancer. Classic FAP phenotype is characterised by >100 colonic polyps primarily affecting the rectum and left colon, with early incidence of the disease starting around age 20 with progression to cancer by age 40.¹ Extracolonic intestinal manifestations include gastric fundic gland hyperplastic polyps and duodenal adenomas.² Extraintestinal manifestations include desmoid tumours, osteomas, congenital hypertrophy of the retinal pigment epithelium and thyroid, adrenal and hepatobiliary cancers.³ APC is a tumour suppressor gene located on chromosome 5q21 and its gene product affects cell signalling through its interactions with β-catenin/Tcf and the Wnt signalling pathway.⁴ APC codes for a 2843 aminoacid protein, with pathogenic mutations most often occurring between codons 168 and 1580 and greatest frequency at mutational hotspot codons 1061 and 1309.^{5 6} Most of these mutations are nonsense or frameshift mutations that yield a truncated protein product.⁷

Attenuated familial adenomatous polyposis (AFAP) is a recognised variant of this disease, associated with the following phenotypic features: fewer than 100 colonic polyps, right-sided colonic predominance and later onset of polyposis (usually age 35–45).⁸ Additionally, extracolonic and extraintestinal manifestations are rarer. AFAP-associated mutations in APC have largely been found before codon 157, in exon 9 or after codon 1595.^{6 7} The MutY homologue gene (MutYH) is responsible for base excision repair, and has known pathogenic mutations also associated with the AFAP phenotype.⁹

We present the case of a 44-year-old man incidentally found to have numerous gastric polyps during bariatric surgery, with subsequent workup demonstrating AFAP phenotype. After undergoing genetic testing, this patient was found to have a novel mutation in APC previously undescribed in literature and was treated surgically.

Case presentation

A 44-year-old super-morbidly-obese man body mass index (BMI 63) underwent sleeve gastrectomy for weight loss and was found to have multiple adenomatous fundic gland polyps on final pathology (figure 1). Subsequent workup included esophagogastroduodenoscopy which revealed innumerable polyps of the remaining gastric fundus and body consistent with fundic gland polyps, normal duodenum without polyps, and Barrett’s oesophagus...