Hereditary diffuse gastric cancer is a rare, autosomal dominant hereditary cancer syndrome associated with germline mutations in CDH 1 in which 60% - 80% of affected individuals develop advanced diffuse gastric cancer, many as young adults. At clinical presentation, ~90% of these malignancies represent advanced, surgically incurable disease. As such, presymptomatic identification of germline CDH 1 mutation carriers followed by early prophylactic total gastric tomy is the sole effective management strategy available. DNA sequence analysis of the CDH 1 gene to identify the af fected germline allele is the diagnostic standard of care; however, CDH 1 ’ s relatively high frequency of polymorphisms and the limited amount of experience available regarding them dictate that many identified variants are, as yet, of un known clinical significance. Given the dramatic consequences of inappropriately offered or withheld treatment, careful clinical selection of at-risk individuals is critical. To facilitate this, multiple groups have published screening criteria recommendations, and while there is disagreement regarding the optimal diagnostic approach, the most widely-used overlap to a considerable degree.
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