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

Dig Liver Dis. 2012 Nov;44(11):952-6. doi: 10.1016/j.dld.2012.05.019. Epub 2012 Jun 27.

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.

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Female
  • Gastric Mucosa / metabolism*
  • Gastritis, Hypertrophic / complications
  • Gastritis, Hypertrophic / genetics*
  • Gastritis, Hypertrophic / metabolism
  • Gene Expression Regulation
  • Helicobacter Infections / complications
  • Helicobacter Infections / metabolism
  • Helicobacter pylori
  • Homeodomain Proteins / metabolism*
  • Humans
  • Intestinal Polyposis / complications
  • Intestinal Polyposis / congenital*
  • Intestinal Polyposis / genetics
  • Intestinal Polyposis / metabolism
  • Male
  • Neoplastic Syndromes, Hereditary / complications
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / metabolism
  • Pedigree
  • Smad4 Protein / genetics*
  • Smad4 Protein / physiology
  • Trans-Activators / metabolism*
  • Transforming Growth Factor alpha / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology
  • Up-Regulation

Substances

  • Homeodomain Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • pancreatic and duodenal homeobox 1 protein

Supplementary concepts

  • Juvenile polyposis syndrome