Hereditary mixed polyposis syndrome is a rare colon cancer predisposition syndrome caused by a duplication of a noncoding sequence near the gremlin 1, DAN family BMP antagonist gene (GREM1) originally described in Ashkenazi Jews. Few families with GREM1 duplications have been described, so there are many questions about detection and management. We report 4 extended families with the duplication near GREM1 previously found in Ashkenazi Jews; 3 families were identified at cancer genetic clinics in Israel and 1 family was identified in a cohort of patients with familial colorectal cancer. Their clinical features include extracolonic tumors, onset of polyps in adolescence, and rapid progression of some polyps to advanced adenomas. One family met diagnostic criteria for Lynch syndrome. Expansion of the hereditary mixed polyposis syndrome phenotype can inform surveillance strategies for carriers of GREM1 duplications.
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CRC, Colon Cancer Susceptibility, HMPS1, Polyposis, Adenomatous Polyposis Coli, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Colon, Colonoscopy, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mutational Analysis, Disease Progression, Early Detection of Cancer, Female, Gene Duplication, Genetic Predisposition to Disease, Heredity, Humans, Intercellular Signaling Peptides and Proteins, Israel, Jews, Male, Middle Aged, Molecular Diagnostic Techniques, Mutation, Pedigree, Phenotype, Time Factors, Young Adult