Adenomatous polyposis syndromes: Unexplained colorectal adenomatous polyposis

Abstract

In a considerable number of patients with clinically confirmed colorectal adenomatous polyposis, no germline mutation in known genes can be identified, although a genetic etiology is likely. The phenotype of these cases is characterized by a more attenuated course, no evident extracolonic manifestations, and an unsuspicious or unclear family history in at least half of the patients. Diagnostic and technical difficulties to identify mutations in established genes might be relevant, in particular low-level APC mutational mosaicism seems to be the underlying cause in a large fraction of unexplained cases. During the last decades, several efforts had been made to uncover further genetic causes. Using different approaches including exome sequencing, however, only few and very rare novel genetic subtypes could be delineated pointing to extreme genetic heterogeneity. Consequently, large cohorts provided by international collaborations and novel analytic strategies are required to uncover the genetic basis in those patients.