Pathogenic variants (disease-causing) in the PDGFRA gene can increase the risk of developing gastrointestinal stromal tumors (GISTs), a type of sarcoma that develops in the connective tissue of the digestive tract. GISTs can form anywhere along the GI tract, including the stomach, small intestine, colon/rectum, and esophagus, and can range from slow-growing to more aggressive. In some individuals with PDGFRA variants, additional physical features, such as coarse facial characteristics or large hands and feet, have been reported, though these features are not seen in everyone. Management of PDGFRA–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. PDGFRA variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in PDGFRA 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
