Pathogenic variants (disease-causing) in the CDH1 gene are associated with Hereditary Diffuse Gastric and Lobular Breast Cancer (HDGLBC) syndrome. Individuals with CDH1 pathogenic variants have a high lifetime risk of diffuse gastric cancer, an aggressive form of gastric cancer. Women also have a significantly increased risk of lobular breast cancer. Management of CDH1–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early as well as risk-reducing options (surgery and medication). CDH1 variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in CDH1 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.
In addition, pathogenic variants in CDH1 can sometimes cause blepharocheilodontic syndrome type 1, a rare autosomal dominant disorder characterized by several changes to the eyelids, bilateral cleft lip and palate, and conical teeth.
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Written December 2025
