Melena Revealing an Attenuated Familial Adenomatous Polyposis in an Elderly Patient: A Case Report

We describe a patient who was diagnosed with multiple tubulleuvillous adenomas with focus of high-grade tubular dysplasia all over the colonic mucosa, discovered during a colonoscopy performed during an episode of melena. Genetic testing has identified a germline truncating mutation at the codon (5q22.2) of the adenomatous polyposis (APC) gene. This mutation is localized in the alternately spliced region of exon 12, a region which is associated with an attenuated familial adenomatous polyposis (PAFA) phenotype. Our patient had no extracolic manifestations of PAFA and none of her relatives had a history of rectocolic polyposis. Treatment consisted of colectomy with ileorectal anastomosis. PAFA is an ill-defined condition of unknown prevalence and penetrance, requiring individual treatment and lifelong monitoring. It is essential to identify these patients with a view to setting up appropriate endoscopic surveillance at an early age in family members carrying this mutation, due to the marked intra-family phenotypic variance.

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

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome associated with mutation in the adenomatous polyposis coli (APC) gene, a tumour suppressor located on chromosome 5q21. Attenuated familial adenomatous polyposis (AFAP) is a variant associated with fewer and later onset of colon polyps. AFAP-associated APC mutations have largely been found before codon 157, in exon 9 or after codon 1595. We present the case of a 44-year-old man incidentally found to have numerous gastric polyps during bariatric surgery, with innumerable polyps in the remaining part of the stomach and the entire colon, with rectal sparing, consistent with AFAP phenotype. Genetic testing demonstrated the c.7682dup (p.Ser2562Lysfs*21) variant in exon 15 of APC. This represents a previously undescribed APC mutation. This mutation likely yields end-binding protein 1 and human disc large binding protein inactivation, causing cell cycle microtubule dysregulation and tumour suppressor inactivation. Through loss of these regulatory mechanisms, this mutation is associated with AFAP phenotype. The patient was treated surgically and is doing well.

Appropriate Management of Attenuated Familial Adenomatous Polyposis: Report of a Case and Review of the Literature

Hereditary polyposis syndromes in which APC gene germline mutations can lead to colorectal carcinogenesis are familial adenomatous polyposis (FAP), attenuated FAP (AFAP) and MUTYH-associated polyposis. All 3 syndromes increase the potential for the development of colorectal cancer. AFAP is diagnosed if less than 100 adenomas are detected in the colon at presentation. AFAP is inherited in an autosomal dominant manner. We present a case of a 22-year-old female with AFAP who was treated with endoscopic polypectomy and surveilled by annual colonoscopy. Guidelines for AFAP surveillance suggest annual colonoscopy with endoscopic polypectomy in asymptomatic individuals. Indications for immediate surgery include documented or suspected cancer or significant symptoms. Preferred surgical option in AFAP is colectomy and ileo-rectal anastomosis. Surveillance of the AFAP patients should include upper GI endoscopy and duodenoscopy with random biopsies of fundic gland polyps and endoscopic resection of detected adenomas. Annual thyroid ultrasound is indicated due to increased risk for thyroid cancer. In pediatric patients tested positive for germline mutation of APC gene screening for hepatoblastoma using alpha-fetoprotein and liver ultrasound should be performed.