MUTYH Associated Polyposis Coli: One Common and One Rare Mutation

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A 52-year-old Caucasian male with no significant medical history presented at our Department of Gastroenterology several years ago with vague complaints of abdominal distension, fecal urgency, and occasional hematochezia. There was no abdominal pain or weight loss. Familial history was unremarkable. Digital rectal examination revealed tumor at the tip of the finger, confirmed by rectoscopy as a fragile, non-obstructive lesion surrounded by multiple small polyps. A colonoscopy was performed which showed approximately 100 small sessile or pedunculated polyps throughout the large bowel. At 9 cm from the anal margin a concentric polypoid mass was identified, showing central ulceration. Pathological examination confirmed the presence of an invasive adenocarcinoma with strong CEA immunoreactivity. Biopsies of other polyps disclosed tubulovillous adenomata. Endoscopic ultrasound examination suggested penetration of the cancerous growth into the muscular layer. No metastatic disease was identified by CT examination of the abdomen. Final staging of the rectal tumor was T3N0M0. Considering the numerous polyps visualized by endoscopy, a tentative diagnosis of familial adenomatous polyposis (FAP) was made. In this case, total colectomy is the only curative treatment. Neo-adjuvant chemoradiation therapy was initiated (5-fluorouracil and Mitomycin) to downstage the lesion. Re-evaluation showed a considerable regression of the main rectal lesion, as well as the multiple colonic polyps. A total colectomy was performed with ileo-anal anastomosis and J-pouch construction. The patient is currently in regular follow-up and has no symptoms or signs of recurrent disease. Familial adenomatous polyposis is caused by mutations in the APC gene (adenomatous polyposis coli) located on chromosome 5. To our surprise, we could not identify the most common APC mutations in our patient. Considering the autosomal dominant inheritance of FAP, colonoscopy was also performed in the patient’s three children and found to be negative. In the meantime, his sister was also diagnosed in another hospital with rectal carcinoma and multiple colonic polyps. She was also treated by total colectomy. Taking into account the more recent scientific evidence, a new DNA analysis was performed in our patient. This showed two mutations of the MUTYH gene (Y165C and P391L). In contrast to FAP, MAP (MUTYH associated polyposis) is inherited in an autosomal recessive pattern, providing a solid explanation for the pedigree of our case.