The hamartomatous polyposis syndromes: a clinical and molecular review

Am J Gastroenterol. 2005 Feb;100(2):476-90. doi: 10.1111/j.1572-0241.2005.40237.x.

Abstract

Inherited forms of gastrointestinal cancer have been a major focus of study and advancement over the past decade. Familial adenomatous polyposis and hereditary nonpolyposis colon cancer are the two most common heritable colon cancer syndromes. Inherited polyposis syndromes are characterized by the dominant type of polyp (whether adenomatous or hamartomatous) present and by the polyp's location within the gastrointestinal tract. The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. They represent a small but appreciable number of the gastrointestinal inherited cancer predisposition syndromes; it is now known that many of these syndromes carry a substantial risk for developing colon cancer as well as other gastrointestinal and pancreatic cancers. Patients afflicted with these syndromes are also at significant risk for extraintestinal malignancies. Seven inherited hamartomatous polyposis syndromes have been described: familial juvenile polyposis syndrome, Cowden's syndrome, Bannayan-Ruvalcaba-Riley syndrome, Peutz-Jeghers syndrome, basal cell nevus syndrome, neurofibromatosis 1, and multiple endocrine neoplasia syndrome 2B. Hereditary mixed polyposis syndrome is a variant of juvenile polyposis characterized by both hamartomatous and adenomatous polyps. The hamartomatous syndromes occur at approximately 1/10th the frequency of the adenomatous syndromes and account for <1% of colorectal cancer in Northern America. While the diagnosis of these inherited syndromes is primarily clinical, genetic testing is now available for all six syndromes. However, there are a significant number of spontaneous mutations seen in each of the syndromes. The management of these patients necessitates a coordinated multidisciplinary approach. The purpose of this review is to characterize the clinical and pathological features of these syndromes and to review the targets of cancer surveillance. The molecular alterations responsible for the inherited hamartomatous polyposis syndromes will also be discussed.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple
  • Adenomatous Polyposis Coli / diagnosis
  • Adenomatous Polyposis Coli / genetics
  • Hamartoma Syndrome, Multiple / diagnosis
  • Hamartoma Syndrome, Multiple / genetics
  • Humans
  • Intestinal Polyps / diagnosis
  • Intestinal Polyps / genetics*
  • Neoplastic Syndromes, Hereditary* / diagnosis
  • Neoplastic Syndromes, Hereditary* / genetics
  • Neurofibromatosis 1 / diagnosis
  • Neurofibromatosis 1 / genetics
  • Peutz-Jeghers Syndrome / diagnosis
  • Peutz-Jeghers Syndrome / genetics
  • Syndrome