The Application of Clinical Genetics (Nov 2021)
Novel Genetic Causes of Gastrointestinal Polyposis Syndromes
Abstract
Anne Marie Jelsig,1 Anna Byrjalsen,1 Majbritt Busk Madsen,2 Tine Plato Kuhlmann,3 Thomas van Overeem Hansen,1 Karin AW Wadt,1,4 John Gásdal Karstensen4,5 1Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark; 2Center for Genomic Medicine, University Hospital of Copenhagen, Copenhagen, Denmark; 3Department of Pathology, University Hospital of Copenhagen, Herlev Hospital, Herlev, Denmark; 4Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 5Danish Polyposis Registry, Gastro Unit, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, DenmarkCorrespondence: Anne Marie JelsigDepartment of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, DenmarkTel +45 20 36 18 85Email [email protected]: 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
