Familial Cancer

, Volume 14, Issue 4, pp 569–573 | Cite as

Massive gastric polyposis associated with a germline SMAD4 gene mutation

  • Eline SoerEmail author
  • Wouter H. de Vos tot Nederveen Cappel
  • Marjolijn J. L. Ligtenberg
  • Freek Moll
  • Robert G. Pierik
  • Juda Vecht
  • Hans F. A. Vasen
  • Antoine Flierman
Original Article


Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98 % of patients) and the stomach (14 %). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endoscopic findings revealed giant rugal folds suggestive of Ménétrier disease. However, as other possible gastropathies could not be differentiated on the basis of histology, a definitive diagnosis of JPS required additional mutation analysis. In patients with polyposis predominant in or limited to the stomach, establishing a diagnosis based solely on the pathological features of polyps can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies. Mutation analysis should be considered early in the diagnostic process in cases of suspected juvenile polyposis, thus facilitating rapid diagnosis and adequate follow-up.


Gastric polyposis Juvenile polyposis SMAD4 mutation 


  1. 1.
    Desai DC, Neal KF, Talbot IC, Nodgson SV, Philips RKS (1995) Juvenile polyposis. Br J Surg 82:14–17CrossRefPubMedGoogle Scholar
  2. 2.
    Scott-Conner CEH, Hausmann M, Hall TJ, Skelton DS, Anglin BL, Subramony C (1995) Familial juvenile polyposis: patterns of recurrence and implications for surgical management. J Am Coll Surg 181:407–413PubMedGoogle Scholar
  3. 3.
    Larsen Haidle J, Howe JR (1993–2014) Juvenile polyposis syndrome. 2003 May 13 [Updated 2014 May 22]. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews® [Internet]. University of Washington, SeattleGoogle Scholar
  4. 4.
    Howe JR, Sayed MG, Ahmed AF, Ringold J, Larsen-Haidle J, Merg A et al (2004) The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet 41:484–491PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Shikata K, Kukita Y, Matsumoto T, Esaki M, Yao T, Mochizuki Y, Hayashi K, Iida M (2005) Gastric juvenile polyposis associated with germline SMAD4 mutation. Am J Med Genet 134A:326–329CrossRefGoogle Scholar
  6. 6.
    Handra-Luca A, Condroyer C, de Moncuit C, Tepper M, Fléjou JF, Thomas G, Olschwang S (2005) Vessels’ morphology in SMAD4 and BMPR1A-related juvenile polyposis. Am J Med Genet 138A:113–117CrossRefPubMedGoogle Scholar
  7. 7.
    O’Malley M, LaGuardia L, Kalady MF, Parambil J, Heald B, Eng C, Church J, Burke CA (2012) The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum 55:886–892CrossRefPubMedGoogle Scholar
  8. 8.
    Schwenter F, Faughnan ME, Gradinger AB, Berk T, Gryfe R, Pollett A, Cohen Z, Gallinger S, Durno C (2012) Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation. J Gastroenterol 47:795–804CrossRefPubMedGoogle Scholar
  9. 9.
    Pintiliciuc OG, Heresbach D, de-Lajarte-Thirouard AS, Dugast C, Reignier A, Cottereau J, Bretagne JF (2008) Gastric involvement in juvenile polyposis associated with germline SMAD4 mutations: an entity characterized by a mixed hypertrophic and polypoid gastropathy. Gastroen Clin Biol 32(5):445–450Google Scholar
  10. 10.
    Haramis AP, Begthel H, van den Born M, van Es J, Jonkheer S, Offerhaus GJ et al (2004) De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303(5664):1684–1686CrossRefPubMedGoogle Scholar
  11. 11.
    Gallione C, Aylsworth AS, Beis J, Berk T, Bernhardt B, Clark RD et al (2010) Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome. Am J Med Genet 152A:333–339CrossRefPubMedGoogle Scholar
  12. 12.
    Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, Mangold E et al (2002) Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet 111:108–111CrossRefPubMedGoogle Scholar
  13. 13.
    Rich A, Zuluaga Toro T, Tanksley J, Fishe WH, Lind CD, Ayers GD (2010) Distinguishing Ménétrier’s disease from its mimics. Gut 59(12):1617–1624Google Scholar
  14. 14.
    Howe JR, Mitros FA, Summers RW (1998) The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 5:751–756CrossRefPubMedGoogle Scholar
  15. 15.
    Dunlop MG (2002) Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, juvenile polyposis, and Peutz–Jeghers syndrome. Gut 51(Suppl 5):V21–V27PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Postgate AJ, Will OC, Fraser CH, Fitzpatrick A, Philips RK, Clark SK et al (2009) Capsule endoscopy for the small bowel in juvenile polyposis syndrome: a case series. Endoscopy 41(11):1001–1004CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Eline Soer
    • 1
    Email author
  • Wouter H. de Vos tot Nederveen Cappel
    • 1
  • Marjolijn J. L. Ligtenberg
    • 4
  • Freek Moll
    • 2
  • Robert G. Pierik
    • 3
  • Juda Vecht
    • 1
  • Hans F. A. Vasen
    • 5
  • Antoine Flierman
    • 1
  1. 1.Department of Gastroenterology and HepatologyIsala ClinicsZwolleThe Netherlands
  2. 2.Department of PathologyIsala ClinicsZwolleThe Netherlands
  3. 3.Department of SurgeryIsala ClinicsZwolleThe Netherlands
  4. 4.Department of Human GeneticsRadboud University Medical CenterNijmegenThe Netherlands
  5. 5.The Netherlands Foundation for the Detection of Hereditary TumorsLeidenThe Netherlands

Personalised recommendations