Low Yield of Genetic Testing in Serrated Polyposis Syndrome.

[INTRODUCTION] Serrated polyposis syndrome (SPS) is clinically defined by the presence of multiple serrated polyps in the colon and rectum, and is associated with increased colorectal cancer risk. SPS is the most prevalent polyposis condition; however, its genetic basis remains poorly characterized. The British Society of Gastroenterology recommends gene panel testing for all patients with SPS to rule out other polyposis conditions. The aim of this study was to evaluate the diagnostic yield of genetic testing in patients with SPS.

[METHODS] We conducted a retrospective, cross-sectional analysis using the Polyposis Registry from St. Mark's Hospital, London, a national referral center in the United Kingdom. Patients with SPS who underwent genetic testing between April 4, 2009 and February 9, 2024, and met the SPS WHO criteria were included. Genetic variants were identified from test reports, and clinical data were extracted from medical records.

[RESULTS] In total, 573 people with SPS were identified in our registry, of whom 258 underwent genetic testing. Of these, 119 underwent target gene testing and 139 underwent multigene panel testing. No pathogenic variants were detected through targeted genetic testing. On multigene panel testing, pathogenic germline variants were found in 4 patients (2.9%), including 3 with Lynch syndrome (2 with PMS2 , one with MSH2 ) and one with an RNF43 variant.

[DISCUSSION] Genetic testing demonstrated a low diagnostic yield in this SPS cohort, suggesting undefined genetic risk or involvement of other pathophysiological factors. Therefore, genetic testing seems to have limited utility in patients with SPS and may primarily identify those with an incidental diagnosis of Lynch syndrome.