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.

• Authors: Ada Piepoli, Gianluigi Mazzoccoli, Anna Panza, Virginia Tirino, Giuseppe Biscaglia, Annamaria Gentile, Maria Rosa Valvano, Celeste Clemente, Vincenzo Desiderio, Gianpaolo Papaccio, Michele Bisceglia, Angelo Andriulli
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 44 Issue 11 Pg. 952-6 (Nov 2012) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 22748914 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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