The growing complexity of the intestinal polyposis syndromes

Abstract

Familial adenomatous polyposis has been the first form of inherited intestinal polyposis to be recognized. For a long time it has been considered the main polyposis syndrome, associated with an easily recognizable phenotype, with a marginal role attributed to a few very rare hamartomatous conditions. More recently, it has been gradually demonstrated that the intestinal polyposes encompass a range of conditions within a wide spectrum of disease severity, polyp histology, and extraintestinal manifestations. A growing number of genes and phenotypes has been identified, and heterogeneity of somatic molecular pathways underlying epithelial transformation in different syndromes and associated tumors has been documented. Increasing knowledge on the molecular bases and more widespread use of genetic tests has shown phenotypic overlaps between conditions that were previously considered distinct, highlighting diagnostic difficulties. With the advent of next generation sequencing, the diagnosis and the classification of these syndromes will be progressively based more on genetic testing results. However, the phenotypic variability documented among patients with mutations in the same genes cannot be fully explained by different expressivity, indicating a role for as yet unknown modifying factors. Until the latter will be identified, the management of patients with polyposis syndromes should be guided by both clinical and genetic findings. © 2013 Wiley Periodicals, Inc.

Hereditary Gastrointestinal Polyposis Syndromes: A Review Including Newly Identified Syndromes

“…Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous polyposis syndrome [1,[3][4][5][6][7][8][9][10]. This is the second most common hamartomatous polyposis syndrome with an estimated incidence of 1/120,000-1/200,000 live births [3,6,7].…”

“…This is the second most common hamartomatous polyposis syndrome with an estimated incidence of 1/120,000-1/200,000 live births [3,6,7]. The syndrome is characterized and defined by hamartomatous polyps of the gastrointestinal tract, mucocutaneous pigmentation, and an elevated risk for a wide variety of malignancies [1,[3][4][5][6][7][8][9][10].…”

“…The hamartomatous polyps are most common in the small bowel (64-96% of cases) and only slightly less frequent in the stomach (24-49%) and colon (27-53%) [1,3,4,[6][7][8][9][10]. Rarely, polyps occur in other mucosal surfaces including the gallbladder, respiratory tract, and urinary tract [1,6,9,10].…”

“…This phenomenon occurs in approximately 10% of small bowel polyps and should not be misinterpreted as invasive welldifferentiated carcinoma [1,3,4,6,10]. The polyps frequently present with intussusception or obstruction, bleeding, or abdominal pain in the second decade of life [2,6,[7][8][9][10].…”

“…Recently, a new type of polyposis syndrome has been defined and is associated with various types of serrated polyps [2]. Almost all of these syndromes have an increased risk of colorectal cancer and most are associated with an increased risk of a variety of extracolonic tumors, both benign and malignant [1,[3][4][5][6][7][8]. This is a rapidly evolving field with some entities being redefined, some entities having their genetic basis unraveled, and new entities emerging among the polyposis syndromes.…”