SEVERE UPPER GASTROINTESTINAL POLYPOSIS ASSOCIATED WITH SPARSE COLONIC POLYPOSIS IN A FAMILIAL ADENOMATOUS POLYPOSIS FAMILY WITH AN APC MUTATION AT CODON-1520

Background-Familial adenomatous polyposis usually results in colonic p olyposis with hundreds to thousands of polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and variable extracolonic f eatures. Recent reports indicate that patients with distal mutations b etween codons 1445 and 1578 do not express CHRPE and have a high incid ence of desmoid tumours. Patients-The family studied has an unusual ph enotype of sparse colonic polyposis but profuse upper gastrointestinal polyposis. Affected subjects do not have CHRPE. Methods-The protein t runcation test followed by sequencing identified a 2 base pair deletio n at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream. Results-This family demonstrates t hat sparse colonic polyposis but severe upper tract polyposis may be a ssociated with mutations between codons 1445 and 1578. Conclusions-Stu dy of duodenal and colonic polyps in further cases with mutations in t his region is warranted. Such mutations may preferentially cause duode nal adenomas and desmoid tumours as somatic mutations in these tumours also occur in this region, unlike colorectal tumours where somatic mu tations occur more proximally. This study emphasises the importance of screening the upper gastrointestinal tract even when the colonic dise ase is mild.