FaCD Online Syndrome Fact Sheet

Last updated: 25 Mar 2008

Name: Juvenile Polyposis

Synonym: incl.: Juvenile Polyposis of the Stomach

Mode of Inheritance: AD

Genes

BMPR1A, mapped to 10q22.3
ENG, mapped to 9q34.1
PTEN, mapped to 10q23.3
SMAD4/DPC4, mapped to 18q21.1

Tumor features

colorectal hamartomatous polyps
gastric hamartomatous polyps
gastrointestinal cancer
gastrointestinal hamartomas
gastrointestinal polyps, juvenile type
hamartomatous polyps in small intestine
pancreatic adenocarcinoma

Tumor features (possible)

neurofibroma, general

Non-tumor features

mucocutaneous telangiectasia

Comment

Multiple hamartous polyps (sometimes with adenomatous changes[1;2]), lacking smooth muscle, of stomach, small intestine, colon and rectum are the hallmarks of this disorder (JP). Rectal bleeding is the usual presentation in childhood. As opposed to the single sporadic juvenile polyp, juvenile polyposis is associated with an increased risk of colorectal (50-70 % lifetime risk ?), gastric, small bowel and pancreatic cancer[1-12,28].

A number of patients/families have been reported with predominantly gastric involvement (hamartomas as well as carcinomas)[13;14]. It is presently unclear whether or not this represents a separate genetic entity. Patients with gastric juvenile polyposis, initially classified as hyperplastic polyposis, in the presence of germline SMAD4 mutations have been observed[31].
Juvenile polyposis associated with neurofibromatosis [15;16] or hereditary hemorrhagic telangiectasia[17] has been reported a few times. JP has been reported as sporadic cases as well as affected multigeneration families, approximately 20-50% of JP patients have a positive family history. Juvenile polyps may be asymptomatic, so a family history may be false negative[18]. An association of JP with hereditary hemorrhagic telangiectasia has been observed in a few cases[19]. Juvenile polyposis is genetically heterogeneous with mutations in SMAD4[20-23,28], PTEN[24,28], BMPR1A[25,28] and ENG[30]. Other as yet unidentified genes may be involved too. Differential diagnosis includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Gorlin syndrome and familial mixed polyposis. Woodford-Richens et al.[26] conclude that mutations in PTEN, PTCH and SMAD4 are unlikely to cause juvenile polyposis if clinical features suggestive of the first three of these syndromes are absent. With respect to the differential diagnosis: the hamartous polyps in Peutz-Jeghers syndrome differ from those in juvenile polyposis: PJS polyps contain smooth muscle.

Diagnostic criteria[10;17]:
at least one of the following:

• a) 3 or more juvenile type colonic polyps (usually 50-200 are observed)
• b) juvenile polyps throughout the gastrointestinal tract
• c) any number of juvenile polyps in a patient with a family history of juvenile polyposis

Links

The Network for Peutz Jeghers and Juvenile Polyposis Syndrome 24 1 08

References

[1] Subramony C, Scott-Conner CEH, Skelton D, Hall TJ. Familial juvenile polyposis - Study of a kindred: Evolution of polyps and relationship to gastrointestinal carcinoma. Am J Clin Pathol 1994; 102:91-97.
[2] Sharma AK, Sharma SS, Mathur P. Familial juvenile polyposis with adenomatous-carcinomatous change. J Gastroenterol Hepatol 1995; 10:131-134.
[3] Jarvinen H, Franssila KO. Familial juvenile polyposis coli: increased risk of colorectal cancer. Gut 1984; 25:792-800.
[4] Grosfeld JL, West KW. Generalized juvenile poplyposis coli: clinical management based on Long-term observations. Arch Surg 1986; 121:530-534.
[5] 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(1):107-114.
[6] Jass JR, Williams CB, Bussey HJR, Morson BC. Juvenile polyposis- a precancerous condition. Histopathology 1988; 13:619-630.
[7] O'Riordain DS, O'Dwyer PJ, Cullen AF, McDermott EW, Murphy JJ. Familial Juvenile Polyposis Coli and colorectal cancer. Cancer 1991; 68:889-892.
[8] Giardiello FM, Hamilton SR, Kern SE, Offerhaus GJA, Green PA, Celano P, Krush AJ, Booker SV. Colorectal neoplasia in juvenile polyposis or juvenile polyps. Arch Dis Child 1991; 66:971-975.
[9] Scott-Conner CEH, Hausmann M, Hall TJ, Skelton DS, Anglin BL, Subramony C. Familial juvenile Polyposis: Patterns of recurrence and implications for surgical management. J Amer Coll Surgeons 1995; 181:407-413.
[10] Desai DC, Neale KF, Talbot IC, Hodgson SV, Phillips RKS. Juvenile polyposis. Br J Surg 1995; 82:14-17.
[11] Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 5[8], 751-756. 1998. )
[12] Agnifili A, Verzaro R, Gola P, Marino M, Mancini E, Carducci G, Ibi I, Valenti M. Juvenile polyposis: case report and assessment of the neoplastic risk in 271 patients reported in the literature. Dig Surg 1999; 16(2):161-166.
[13] Hizawa K, Iida M, Yao T, Aoyagi K, Fujishima M. Juvenile polyposis of the stomach: clinicopathological features and its malignant potential. J Clin Pathol 50[9], 771-774. 1997.
[14] Höfting I, Pott G, Schrameyer B, Solte M. Familiäre juvenile polyposis mit vorwiegender magenbeteiligung. Z Gastroenterol 1993; 31:480-483.
[15] Mendelsohn G, Diamond MP. Familial ganglioneuromatous polyposis of the large bowel: report of a family with associated juvenile polyposis. Am J Surg Pathol 1984; 8(7):515-520.
[16] Raskin BR, Dodd H. Juvenile polyposis coli concurrent with neurofibromatosis. South Med J 1976; 69(10):1374-1376.
[17] Desai DC, Murday V, Phillips RKS, Neale KF, Milla P, Hodgson SV. A survey of phenotypic features in juvenile polyposis. J Med Genet 1998; 35:476-481.
[18] Hoffenberg EJ, Sauaia A, Maltzman T, Knoll K, Ahnen DJ. Symptomatic colonic polyps in childhood: Not so benign. J Pediatr Gastroenterol Nutr 28[2], 175-181. 1999. )
[19] Inoue S, Matsumoto T, Iida M, Hoshika K, Shimizu M, Hisamoto N, Kihara T. Juvenile polyposis occurring in hereditary hemorrhagic telangiectasia. Am J Med Sci 317[1], 59-62. 1999.
[20] Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IPM, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280[5366], 1086-1088. 1998.
[21] Houlston R, Bevan S, Williams A, Young J, Dunlop M, Rozen P, Eng C, Markie D, Woodford-Richens K, Rodriguez-Bigas MA, Leggett B, Neale K, Phillips R, Sheridan E, Hodgson S, Iwama T, Eccles D, Bodmer W, Tomlinson I. Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. Hum Mol Genet 7[12], 1907-1912. 1998.
[22] Roth S, Sistonen P, Salovaara R, Hemminki A, Loukola A, Johansson M, Avizienyte E, Cleary KA, Lynch P, Amos CI, Kristo P, Mecklin JP, Kellokumpu I, Jarvinen H, Aaltonen LA. SMAD genes in juvenile polyposis. Gene Chrom Cancer 1999; 26(1):54-61.
[23] Friedl W, Kruse R, Uhlhaas S, Stolte M, Schartmann B, Keller KM, Jungck M, Stern M, Loff S, Back W, Propping P, Jenne DE. Frequent 4-bp deletion in exon 9 of the SMAD4/MADH4 gene in familial juvenile polyposis patients. Gene Chrom Cancer 1999; 25(4):403-406.
[24] Olschwang S, Serova-Sinilnikova OM, Lenoir GM, Thomas G. PTEN germ-line mutations in juvenile polyposis coli. Nat Genet 1998; 18:12-13.
[25] Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. NATURE GENETICS 2001; 28(2):184-187.
[26] Woodford-Richens K, Bevan S, Churchman M, Dowling B, Jones D, Norbury CG, Hodgson SV, Desai D, Neale K, Phillips RKS, Young J, Leggett B, Dunlop M, Rozen P, Eng C, Markie D, Rodriguez Bigas MA, Sheridan E, Iwama T, Eccles D, Smith GT, Kim JC, Kim KM, Sampson JR, Evans G, Tejpar S, Bodmer WF, Tomlinson IPM, Houlston RS. Analysis of genetic and phenotypic heterogeneity in juvenile polyposis. Gut 2000; 46(5):656-660.
[27] van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R, Giardiello FM, Offerhaus GJ. Large Genomic Deletions Of Smad4, Bmpr1a And Pten In Juvenile Polyposis.
[28] Brosens LA, van Hattem A, Hylind LM, Iacobuzio-Donahue C, Romans KE, Axilbund J, Cruz-Correa M, Tersmette AC, Offerhaus GJ, Giardiello FM. Risk of colorectal cancer in juvenile polyposis. Gut 2007; 56(7):965-7.
[29] Howe JR, Haidle JL, Lal G, Bair J, Song C, Pechman B, Chinnathambi S, Lynch HT. ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. Clinical genetics 2007; 71(1):91-2.
[30] Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, Khoo SK, Patocs A, Martin C, Bridgeman S, Heinz J, Pilarski R, Lehtonen R, Prior TW, Frebourg T, Teh BT, Marchuk DA, Aaltonen LA, Eng C. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA 2005; 294(19):2465-73.
[31] Pintiliciuc OG, Heresbach D, de-Lajarte-Thirouard AS, Dugast C, Reignier A, Cottereau J, Bretagne JF. Gastric involvement in juvenile polyposis associated with germline SMAD4 mutations: An entity characterized by a mixed hypertrophic and polypoid gastropathy. Gastroenterologie clinique et biologique 2008; .