Novel Genetic Causes of Gastrointestinal Polyposis Syndromes

Abstract

Hereditary polyposis syndromes are characterized by a large number and/or histopathologically specific polyps in the gastrointestinal tract and a high risk of both colorectal cancer and extracolonic cancer at an early age. While the genes responsible for some of the syndromes, eg, APC in familial adenomatous polyposis and STK11 in Peutz-Jeghers syndrome, have been known for decades, novel genetic causes have recently been detected that have shed light on the broader clinical spectrum of syndromes. Genetic diagnoses are important because they can facilitate a personalized surveillance program. Furthermore, at-risk members of the patient’s family can be tested and enrolled in surveillance as needed. In some cases, prenatal diagnostics should be offered. In this paper, we describe the development in germline genetics of the hereditary polyposis syndromes over the last 10–12 years, their clinical characteristics, as well as how to implement genetic analyses in the diagnostic pipeline.

Keywords:

• polyposis
• hereditary
• familial adenomatous polyposis
• cancer
• management

Abbreviations

CRC, colorectal cancer; FAP, familial adenomatous polyposis; GI, gastrointestinal; HPS, hereditary polyposis syndromes; JPS, juvenile polyposis syndrome; MAP, MUTYH-associated polyposis; NGS, next-generation sequencing; PJS, Peutz-Jeghers syndrome; PV, pathogenic variants; WES, whole exome sequencing; WGS, whole-genome sequencing.

Disclosure

Dr Karin AW Wadt reports personal fees from advisory board meetings with MSD and AstraZeneca, outside the submitted work. The authors report no conflicts of interest in this work.