Skip to main content

Advertisement

SpringerLink
Log in

Familial juvenile polyposis syndrome with a novel SMAD4 germline mutation

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Juvenile polyposis syndrome (JPS) is a dominantly inherited disorder characterized by the development of numerous juvenile polyps (JPs) of the gastrointestinal tract, and associated with a mutation of the SMAD4 or BMPR1A gene. Here, we report a mother−daughter case of familial JPS. A 29-year-old female patient with severe iron deficiency anemia and hypoproteinemia had numerous polyps in the stomach and a few polyps in the ileum and colon that were detected endoscopically. Biopsy specimens from the gastric polyps were diagnosed as JPs. The patient underwent a laparoscopy-assisted total gastrectomy, and her anemia and hypoproteinemia improved. Her mother also had multiple JPs in the stomach, duodenum, jejunum, and colon. We then diagnosed them as having familial JPS. Moreover, germline mutation analysis of the 2 patients presented a novel pathogenic SMAD4 variant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Sachatello CR, Pickren JW, Grace JT. Generalized juvenile gastrointestinal polyposis. A hereditary syndrome. Gastroenterology. 1970;58:699–708.

    PubMed  CAS  Google Scholar 

  2. Stemper TJ, Kent TH, Summers RW. Juvenile polyposis and gastrointestinal carcinoma. Ann Intern Med. 1975;83:639–46.

    Article  PubMed  CAS  Google Scholar 

  3. van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R, et al. Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis. Gut. 2008;57:623–7.

    Article  PubMed  Google Scholar 

  4. Calva-Cerqueira D, Chinnathambi S, Pechman B, Bair J, Larsen-Haidle J, Howe JR. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. Clin Gene. 2009;75:79–85.

    Article  CAS  Google Scholar 

  5. Aretz S, Stienen D, Uhlhaas S, Stolte M, Entius MM, Loff S, et al. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Gene. 2007;44:702–9.

    Article  CAS  Google Scholar 

  6. Roth SI, Helwig EB. Juvenile polyps of the colon and rectum. Cancer. 1963;16:468–79.

    Article  PubMed  CAS  Google Scholar 

  7. Aaltonen LA, Jass JR, Howe JR. Juvenile polyposis. In: Hamilton SR, Aaltonen LA, editors. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000. p. 130–2.

    Google Scholar 

  8. Lodewijk Brosens AA, Langeveld D, van Arnout Hattem W, Francis Giardiello M, Johan G, Offerhaus A. Juvenile polyposis syndrome. World J Gastroenterol. 2011;17:4839–44.

    Article  PubMed  Google Scholar 

  9. Schreibman IR, Baker M, Amos C, McGarrity TJ. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol. 2005;100:476–90.

    Article  PubMed  Google Scholar 

  10. Chow E, Macrae F. Review of juvenile polyposis syndrome. J Gastroenterol Hepatol. 2005;20:1634–40.

    Article  PubMed  CAS  Google Scholar 

  11. Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis––a precancerous condition. Histopathology. 1988;13:619–30.

    Article  PubMed  CAS  Google Scholar 

  12. Giardiello FM, Hamilton SR, Kern SE, Offerhaus GJ, Green PA, Celano P, et al. Colorectal neoplasia in juvenile polyposis or juvenile polyps. Arch Dis Child. 1991;66:971–5.

    Article  PubMed  CAS  Google Scholar 

  13. Sachatello CR, Hahn IS, Carrington CB. Juvenile gastrointestinal polyposis in a female infant: report of a case and review of the literature of a recently recognized syndrome. Surgery. 1974;75:203–14.

    Google Scholar 

  14. Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, Blois MC, et al. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Gene. 2006;78:1066–74.

    Article  CAS  Google Scholar 

  15. Menko FH, Kneepkens CM, de Leeuw N, Peeters EA, Van Maldergem L, Kamsteeg EJ, et al. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes. Clin Gene. 2008;74:145–54.

    Article  CAS  Google Scholar 

  16. Stemper TJ, Kent TH, Summers RW. Juvenile polyposis and gastrointestinal carcinoma. A study of a kindred. Ann Intern Med. 1975;83:639–46.

    Article  PubMed  CAS  Google Scholar 

  17. Desai DC, Neale KF, Talbot IC, Hodgson SV, Phillips RK. Juvenile polyposis. Br J Surg. 1995;82:14–7.

    Article  PubMed  CAS  Google Scholar 

  18. McColl I, Busxey HJ, Veale AM, Morson BC. Juvenile polyposis coli. Proc R Soc Med. 1964;57:896–7.

    PubMed  CAS  Google Scholar 

  19. Veale AM, McColl I, Bussey HJ, Morson BC. Juvenile polyposis coli. J Med Gene. 1966;3:5–16.

    Article  CAS  Google Scholar 

  20. Utsunomiya J, Gocho H, Miyanaga T, Hamaguchi E, Kashimure A. Peutz–Jeghers syndrome: its natural course and management. Johns Hopkins Med J. 1975;136:71–82.

    PubMed  CAS  Google Scholar 

  21. Latchford AR, Neale K, Phillips RK, Clark SK. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum. 2012;10:1038–43.

    Article  Google Scholar 

  22. Farmer RG, Hawk WA, Turnbull RB Jr. The spectrum of the Peutz–Jeghers syndrome. Report of 3 cases. Am J Dig Dis. 1963;8:953–61.

    Article  PubMed  CAS  Google Scholar 

  23. Bartholomew LG, Moore CE, Dahlin DC, Waugh JM. Intestinal polyposis associated with mucocutaneous pigmentation. Surg Gynecol Obstet. 1962;115:1–11.

    PubMed  CAS  Google Scholar 

  24. Bülow S. Results of national registration of familial adenomatous polyposis. Gut. 2003;52:742–6.

    Article  PubMed  Google Scholar 

  25. Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294:2465–73.

    Article  PubMed  CAS  Google Scholar 

  26. Waite KA, Eng C. From developmental disorder to heritable cancer: it’s all in the BMP/TGF-beta family. Nat Rev Gene. 2003;4:763–73.

    Article  CAS  Google Scholar 

  27. Wang J, Sun L, Myeroff L, Wang X, Gentry LE, Yang J, et al. Demonstration that mutation of the type II transforming growth factor beta receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells. J Biol Chem. 1995;270:22044–9.

    Article  PubMed  CAS  Google Scholar 

  28. Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, et al. Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Gene. 2002;111:108–11.

    Article  CAS  Google Scholar 

  29. Takaku K, Miyoshi H, Matsunaga A, Oshima M, Sasaki N, Taketo MM. Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Can Res. 1999;59:6113–7.

    CAS  Google Scholar 

  30. Taketo MM, Takaku K. Gastrointestinal tumorigenesis in Smad4 (Dpc4) mutant mice. Hum Cell. 2000;13:85–95.

    PubMed  CAS  Google Scholar 

  31. Mishina Y, Suzuki A, Ueno N, Behringer RR. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Gen Dev. 1995;9:3027–37.

    Article  CAS  Google Scholar 

  32. Schwetz V, Uhrig S, Spuller E, Deutschmann A, Högenauer C. Manifestations of juvenile polyposis syndrome in SMAD4 mutation carriers of a kindred. Eur J Gastroenterol Hepatol. 2012;24:988–94.

    Article  PubMed  Google Scholar 

  33. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004;13:852–9.

    Article  Google Scholar 

  34. Schwenter F, Faughnan ME, Gradinger AB, Berk T, Gryfe R, Pollett A, et al. Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation. J Gastroenterol. 2012;47:795–804.

    Article  PubMed  CAS  Google Scholar 

  35. Jass J. Pathology of polyposis syndromes with special reference to juvenile polyposis. In: Utsonomiya J, Lynch H, editors. Hereditary colorectal cancer. Tokyo: Springer; 1990. p. 343–50.

    Google Scholar 

  36. Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol. 1998;5:751–6.

    Article  PubMed  CAS  Google Scholar 

  37. Howe JR, Ringold JC, Hughes JH, Summers RW. Direct genetic testing for Smad4 mutations in patients at risk for juvenile polyposis. Surgery. 1999;126:162–70.

    Article  PubMed  CAS  Google Scholar 

  38. Brosens LA, van Hattem A, Hylind LM, Iacobuzio-Donahue C, Romans KE, Axilbund J, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56:965–7.

    Article  PubMed  Google Scholar 

  39. Scott-Conner CE, Hausmann M, Hall TJ, Skelton DS, Anglin BL, Subramony C. Familial juvenile polyposis: patterns of recurrence and implications for surgical management. J Am Coll Surg. 1995;181:407–13.

    PubMed  CAS  Google Scholar 

  40. Gammon A, Jasperson K, Kohlmann W, Burt RW. Hamartomatous polyposis syndromes. Best Pract Res Clin Gastroenterol. 2009;23:219–31.

    Article  PubMed  CAS  Google Scholar 

  41. Postgate AJ, Will OC, Fraser CH, Fitzpatrick A, Phillips RK, Clark SK. Capsule endoscopy for the small bowel in juvenile polyposis syndrome: a case series. Endoscopy. 2009;41:1001–4.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Sakurai (Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan) for his advice regarding the gene mutation analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Endoscopy, Niigata University Medical and Dental Hospital, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, 951-8510, Japan

    Yutaka Honda, Masaaki Kobayashi, Rintaro Narisawa & Yusuke Kawauchi

  2. Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, 951-8510, Japan

    Yuichi Sato, Takahiro Hoshi & Yutaka Aoyagi

  3. Department of Gastroenterology, Niigata University Medical and Dental Hospital, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, 951-8510, Japan

    Junji Yokoyama

  4. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata City, 951-8510, Japan

    Kazuhito Yajima, Tatsuo Kanda & Katsuyoshi Hatakeyama

  5. Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, 951-8510, Japan

    Yoichi Ajioka

Authors
  1. Yutaka Honda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junji Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masaaki Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rintaro Narisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yusuke Kawauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takahiro Hoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuhito Yajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tatsuo Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoichi Ajioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Katsuyoshi Hatakeyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yutaka Aoyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yutaka Honda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Honda, Y., Sato, Y., Yokoyama, J. et al. Familial juvenile polyposis syndrome with a novel SMAD4 germline mutation . Clin J Gastroenterol 6, 361–367 (2013). https://doi.org/10.1007/s12328-013-0413-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-013-0413-y

Keywords

Search

Navigation