Attenuated Familial Adenomatous Polyposis: A Phenotypic Diagnosis but Obsolete Term?

BACKGROUND: Attenuated familial adenomatous polyposis is characterised by low number (<= 100) and delayed development of colorectal adenomas. Various definitions have been used, and genotype-phenotype correlations have been suggested. OBJECTIVE: We aimed to evaluate phenotypic and genotypic correlation in patients with presumed attenuated familial adenomatous polyposis and assess familial variability. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a tertiary polyposis registry. PATIENTS: Individuals with attenuated familial adenomatous polyposis were identified. Phenotypic group was defined as 100 or fewer adenomas at age 25 years and genotypic group was defined as a variant in the adenomatous polyposis coli region associated with attenuated familial adenomatous polyposis. Pathology polyp count was used for patients who had undergone surgery and endoscopic polyp count for those with intact colon. MAIN OUTCOME MEASURES: We evaluated phenotypic and genotypic correlation in patients with presumed attenuated familial adenomatous polyposis and familial variability. RESULTS: A total of 69 patients were identified in the phenotypic group, of whom 54 (78%) had a pathogenic variant in the attenuated regions of the adenomatous polyposis coli gene. Forty-eight (70%) had intact colon (median age at last colonoscopy 43 [25-73] years; median endoscopic polyp count 20 [0-100]) and 21 (30%) had undergone colectomy (median age at surgery 45 [25-54] years; median pathology polyp count 43 [3-100]). Eighty-three patients were identified in the genotypic group of which 54 (65%) had attenuated phenotype. Inter- and intrafamilial variability were observed. LIMITATIONS: This study was limited by its retrospective nature and single-center experience. CONCLUSION: Phenotype in familial adenomatous polyposis lies on a spectrum and is determined in part by genotype and age at adenoma count. Diagnosis of attenuated familial adenomatous polyposis should be based on phenotype; genotype is not a reliable indicator. Management should be personalized according to the phenotype of each individual.