A unifying working hypothesis for juvenile polyposis syndrome and Ménétrier's disease: Specific localization or concomitant occurrence of a separate entity?

Abstract: Background: Juvenile polyposis syndrome with gastric involvement may mimic Ménétrier''s disease, which is correlated to transforming growth factor (TGF)α overproduction and PDX1 upregulation in the gastric fundus. Aim: We report a family with juvenile polyposis syndrome where one member showed typical features of Ménétrier''s disease and concomitant Helicobacter pylori infection. Methods: We studied a 31-year-old woman belonging to a family with juvenile polyposis syndrome, who exhibited a particular form of hyperplastic gastropathy diagnosed as Ménétrier''s disease with Helicobacter pylori infection. Results: TGFα overexpression and undetectable PDX1 expression were demonstrated in the fundic gastric biopsy specimens. In all affected members of the family we identified a 4-bp deletion in exon 9 of SMAD4 gene, a mutation usually associated with a more virulent form of juvenile polyposis syndrome with a higher incidence of gastric and colonic polyposis. Conclusion: To explain the association of juvenile polyposis syndrome with Ménétrier''s disease we hypothesized a new mechanism that involves TGFβ-SMAD4 pathway inactivation and TGFα overexpression related to Helicobacter pylori infection. [Copyright &y& Elsevier]