Juvenile polyposis syndrome
- Daniel C Chung, MD
Daniel C Chung, MD
- Associate Professor of Medicine
- Harvard Medical School
- Tomer Adar, MD
Tomer Adar, MD
- Research Fellow, Gastroenterology Division
- Massachusetts General Hospital
- Senior Gastroenterologist, Digestive Diseases Institute
- Senior Physician in Internal Medicine, Shaare-Zedek Medical Center
- Hebrew University, Jerusalem, Israel
- Section Editors
- J Thomas Lamont, MD
J Thomas Lamont, MD
- Editor-in-Chief — Gastroenterology and Hepatology
- Section Editor — Anorectal Disorders and Misc. Lower GI Disease; Nutrition, Malabsorption, and Misc. Upper GI Disease
- Professor of Medicine
- Harvard Medical School
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Department Chair, Gynecologic Oncology
- University of Washington Medical Center
Juvenile polyposis syndrome (JPS) is an autosomal dominant condition characterized by multiple hamartomatous polyps throughout the gastrointestinal tract. Individuals with JPS are at increased risk for colorectal and gastric cancer [1,2]. In contrast to JPS, sporadic juvenile polyps of the colon occur in up to 2 percent of children under the age of 10 years, are usually solitary, and are not associated with an increased cancer risk .
This topic will review the clinical manifestations, diagnosis, and management of JPS. The clinical manifestations and diagnosis of other hamartomatous polyposis syndromes (eg, Peutz-Jeghers syndrome, Cowden syndrome, and Bannayan-Riley-Ruvalcaba syndrome) and adenomatous polyposis syndromes (eg, familial adenomatous polyposis and MUTYH-associated polyposis) are discussed in detail, separately . (See "Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis" and "PTEN hamartoma tumor syndrome, including Cowden syndrome" and "Clinical manifestations and diagnosis of familial adenomatous polyposis" and "MUTYH-associated polyposis".)
JPS is rare, with an estimated incidence of 1 in 100,000 to 160,000 individuals .
JPS is an autosomal dominant condition with incomplete penetrance . JPS occurs as a result of germline mutations in the SMAD4 (MADH4) or bone morphogenetic protein receptor type-1A (BMPR1A) genes, which are related to the transforming growth factor-beta (TGF-beta) signaling pathway [6,7]. Mutations in SMAD4 or BMPR1A are identified in approximately 60 percent of JPS patients. Approximately 25 percent of patients have de novo mutations [8,9].
The SMAD4 gene is located on chromosome 18q21.1 and encodes for a cytoplasmic mediator of the TGF-beta signaling pathway. SMAD4 forms heteromeric complexes with other proteins of the SMAD family, and these complexes then act within the nucleus [5,10].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Latchford AR, Neale K, Phillips RK, Clark SK. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum 2012; 55:1038.
- MCCOLL I, BUSXEY HJ, VEALE AM, MORSON BC. JUVENILE POLYPOSIS COLI. Proc R Soc Med 1964; 57:896.
- Zbuk KM, Eng C. Hamartomatous polyposis syndromes. Nat Clin Pract Gastroenterol Hepatol 2007; 4:492.
- Harned RK, Buck JL, Sobin LH. The hamartomatous polyposis syndromes: clinical and radiologic features. AJR Am J Roentgenol 1995; 164:565.
- Chow E, Macrae F. A review of juvenile polyposis syndrome. J Gastroenterol Hepatol 2005; 20:1634.
- Howe JR, Roth S, Ringold JC, et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 1998; 280:1086.
- Fogt F, Brown CA, Badizadegan K, et al. Low prevalence of loss of heterozygosity and SMAD4 mutations in sporadic and familial juvenile polyposis syndrome-associated juvenile polyps. Am J Gastroenterol 2004; 99:2025.
- Burger B, Uhlhaas S, Mangold E, et al. Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposis. Am J Med Genet 2002; 110:289.
- Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110:223.
- Howe JR, Bair JL, Sayed MG, et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 2001; 28:184.
- Sayed MG, Ahmed AF, Ringold JR, et al. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol 2002; 9:901.
- Gallione CJ, Repetto GM, Legius E, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 2004; 363:852.
- O'Malley M, LaGuardia L, Kalady MF, et al. The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum 2012; 55:886.
- Howe JR, Haidle JL, Lal G, et al. ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. Clin Genet 2007; 71:91.
- Sweet K, Willis J, Zhou XP, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA 2005; 294:2465.
- Grotsky HW, Rickert RR, Smith WD, Newsome JF. Familial juvenile polyposis coli. A clinical and pathologic study of a large kindred. Gastroenterology 1982; 82:494.
- Brosens LA, Langeveld D, van Hattem WA, et al. Juvenile polyposis syndrome. World J Gastroenterol 2011; 17:4839.
- Schreibman IR, Baker M, Amos C, McGarrity TJ. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 2005; 100:476.
- Brosens LA, van Hattem A, Hylind LM, et al. Risk of colorectal cancer in juvenile polyposis. Gut 2007; 56:965.
- Beggs AD, Latchford AR, Vasen HF, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 2010; 59:975.
- Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 2008; 3:32.
- Dunlop MG, British Society for Gastroenterology, Association of Coloproctology for Great Britain and Ireland. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 2002; 51 Suppl 5:V21.
- National Comprehensive Cancer Network Clinical Practice Guidlines in Oncology. Genetic/Familial High Risk Assessment: Colorectal. http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf (Accessed on November 13, 2015).
- Shovlin CL, Guttmacher AE, Buscarini E, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000; 91:66.
- CLINICAL FEATURES
- Gastrointestinal manifestations
- - Endoscopic and pathological features
- Cancer risk
- Associated conditions
- DIFFERENTIAL DIAGNOSIS
- Routine evaluation
- Cancer screening
- - Colorectal
- - Upper gastrointestinal tract
- Management of gastrointestinal tract polyps
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS