Genetics of the hamartomatous polyposis syndromes: a molecular review

Hamartomatous polyposis syndromes are a heterogeneous group of disorders that are inherited in an autosomal dominant fashion. These syndromes only represent a small number of the inherited gastrointestinal cancer predisposition syndromes. However, many of these syndromes carry a substantial risk for developing colorectal cancer, as well as extra-colonic malignancy.

We searched for articles on inherited hamartomatous polyposis syndromes, including familial juvenile polyposis syndrome, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, multiple endocrine neoplasia syndrome 2B, hereditary mixed polyposis syndrome, Cronkhite-Canada syndrome, basal cell nevus syndrome, and neurofibromatosis 1, in PubMed, Embase, and Elsevier ScienceDirect. In this review, we briefly discuss the diagnosis and clinical features of these disorders and the molecular alterations responsible for these syndromes.

Given the clinical similarities of these hamartomatous syndromes and the autosomal dominant pattern of inheritance, it is sometimes difficult to differentiate hamartomatous polyps, especially with atypical presentation. The molecular analysis and diagnosis make it possible to identify the subtype of these syndromes. In addition, these tests raise an intriguing possibility that surveillance and early medical intervention will allow for the identification of at-risk patients and the reduction of morbidity and mortality.