gms | German Medical Science

The polyposis phenotype in patients with 10 to 100 colorectal adenomas is often referred to as attenuated familial adenomatous polyposis (AFAP) or multiple colorectal adenomas (MCA). However, these terms delineate a heterogeneous and yet poorly characterised entity. Usually, both adenomas and colorectal cancer (CRC) occur later than in typical familial adenomatous polyposis (FAP), extraintestinal lesions are rarely observed, and most cases are sporadic. In contrast to typical FAP, APC germline mutations were detected in only 20–30% of the attenuated cases. MUTYH-associated polyposis (MAP), a recently described autosomal-recessive inherited adenomatous polyposis syndrome, represents another important etiological fraction: Biallelic MUTYH (MYH) germline mutations were identified in around 15-20% of all patients with an attenuated course. MAP should be considered as an important differential diagnosis to AFAP since the mode of inheritance has consequences with respect to risk prediction in siblings and offspring of MAP patients and the diagnostic procedure in patients with an attenuated adenomatous polyposis. Careful pedigree evaluation is necessary, since vertical transmission can be pretended by unproven cases of colorectal cancer in antecedents. The most striking feature of MAP is rather the later age of onset than the polyp number; duodenal polyposis seems to be quite frequent and sometimes severe, extraintestinal manifestations are uncommon. The risk of CRC is high, thus, regular colonoscopic screening and prophylactic colectomy are important for cancer prevention. As in (A)FAP, surgical therapy should depend on clinical and endoscopic findings rather than on mutation analysis. The CRC risk in patients with a monoallelic MUTYH mutation is likely to be low. The implications of MAP for surveillance and genetic counselling of patients and their relatives will be discussed. The work was supported by the Deutsche Krebshilfe