Double heterozygous pathogenic germline APC and MSH2 variants in a 16-year-old female diagnosed with colorectal cancer
Year: 2026
Type: article
Study design: Case Report
Abstract: Germline pathogenic variants (PVs) of the APC gene cause familial adenomatous polyposis (FAP), whereas PVs in DNA mismatch repair (MMR) genes underlie Lynch Syndrome (LS), formerly known as hereditary non polyposis colorectal cancer (HNPCC). The coexistence of both hereditary syndromes in a single individual has been reported extremely rarely and only in a few patients, and the scant literature on this topic suggests an earlier onset and a more rapidly worsening form of colorectal cancer, compared with subjects who carry a single mutation. Here we describe a 16-year-old female who presented with multiple colonic polyps as well as an invasive colorectal carcinoma, and was found to harbor heterozygous pathogenic variants (PV) both in APC and MSH2 genes. Our patient also represents the unique reported case harboring both a MSH2-EPCAM large rearrangement in association with a frameshift APC PV. This case illustrates the unique clinical phenotype that can arise from simultaneous FAP and LS pathogenic mutations, highlights the importance of comprehensive genetic testing in young patients with aggressive disease and ultimately suggests a personalized follow-up and surveillance program in this case.
Source: Familial Cancer
Authors: Elena Maccaroni, Riccardo Bacalini, Alessia Lancianese, Cecilia Copparoni, Riccardo Giampieri, Francesca Bianchi, Cristiana Brugiati, Laura Belvederesi, Elisa Ambrosini, Natalia Chiodi, Emma Nicol Serritelli, Giulia Ricci, Valentina Tarantino, Manuela Santarosa, Francesca Morgese, Alice Magnarini, Silvia Villani, Veronica Agostinelli, Giulia Mentrasti, Alessandra Mandolesi, Gaia Goteri, Paola Coccia, Rossana Berardi
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,990
OpenAlex ID: W7225018911