Pathogenic variants (disease-causing) in the GREM1 gene cause Hereditary Mixed Polyposis Syndrome (HMPS), which is characterized by multiple and mixed types of colorectal polyps and an increased risk of colorectal cancer. Risk for developing colorectal cancer is 2-5 fold higher than average, but specific cancer risk varies between families and by the variant. Management of GREM1–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. HMPS is more common in the Ashkenazi Jewish population and is thought to occur in ~1% of the population.
Pathogenic variants in GREM1 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
