Thursday 11 March 2004
Juvenile polyposis syndrome; JPS; JPD; Juvenile polyposis disease; digestive juvenile polyposis
Autosomal dominant disease.
JPS presents in childhood or adulthood with a history of rectal bleeding. The juvenile polyps may be limited to the colorectum or generalized throughout the gastrointestinal tract. Rarely, the stomach is the principal site of involvement.
Juvenile polyps are characterized by an overgrowth of an edematous lamina propria containing glands showing cystic dilatation (mucous retention cysts) and occasionally a serrated architecture.
The polyps are typically spherical with an eroded surface epithelium.
Single or small numbers of juvenile polyps are a relatively common occurrence within the colorectum of young children.
There may be extra-intestinal defects, including abnormalities of the cranium or heart, cleft palate, polydactyly, and intestinal malrotations.
Familial clustering indicative of an autosomal dominant mode of inheritance has been described.
A rare form of juvenile polyposis occurs in infancy and is associated with severe diarrhea, hemorrhage, malnutrition, intussusception, and death at an early age. There is no family history.
In JPS, polyps number may range from 5 to 200. The syndromic polyps may differ morphologically from the "classical juvenile polyp".
Such atypical juvenile polyps are multilobated and show a relative lack of the expanded lamina propria.
The surface epithelium is rarely eroded (as is the case for single juvenile polyps), and there may be focal dysplasia accounting for the increased risk of malignancy.
Co-existing adenomas may occur.
The apparently normal mucosa between established polyps may show the earliest morphological changes in the form of mild active inflammation within an edematous lamina propria and slight crypt dilatation.
Progression to a small polyp may not be marked by overt cystic change, and persisting chronic inflammation may render these small lesions indistinguishable from inflammatory polyps.
Edematous expansion of the lamina propria is also seen in Cronkhite-Canada syndrome, but the mucosal involvement in the latter is diffusely nodular without the formation of discrete polyps.
Colorectal cancer risk
There is an increased risk of colorectal cancer, the cumulative risk being estimated as 68% by 60 years of age. A lower estimate of cumulative risk (39%) is likely to be conservative.
In the latter survey, some patients with partial colectomy for colorectal cancer developed additional cancers in the retained rectum. It may be possible to manage patients conservatively if polyps are not numerous.
However, based on estimates of colorectal cancer risk, factors such as progression to dysplasia would lower the threshold for recommending preventive surgery.
Colorectal cancers are often mucinous and/or poorly differentiated and may evolve without an obvious dysplastic transition.
See also : juvenile polyposis with high grade dysplasia
multiple digestive juvenile polyps
- gastric juvenile polyps
- colorectal juvenile polyps
mutations in the MADH4 (SMAD4/DPC4) gene (MIM.600993) located on 18q21.1
mutations in the gene encoding bone morphogenetic protein receptor 1A (BMPR1A) (MIM.601299)
The majority of JPS families have a germline mutation in either SMAD4/DPC4 on chromosome 18q21 or the BMPR1A/ALK3 gene on chromosome 10q23.
The frequency of SMAD4 germline mutation has ranged from 20% to >50% of subjects with JPS.
In one study, 32/54 JPS probands lacked a germline mutation in either SMAD4 or BMPR1A, but there was a more severe phenotype and a higher frequency of a positive family history in probands with germline mutation of either SMAD4 or BMPR1A.
Germline mutation in SMAD4 has also been associated with atypical colorectal juvenile polyps with a high epithelium:stroma ratio, and also with gastric involvement.
The BMP receptor 1A signals via SMAD4 to downregulate cell growth and division, thereby providing an explanation for the similar phenotypes.
However, loss of epithelial expression of SMAD4 protein is found only in polyps from subjects with germline mutation of SMAD4.
The PTEN gene was initially linked with JPS but subsequently with CS.
In fact, this may not exclude PTEN involvement in some cases of JPS since large deletions in 10q implicating both BMPR1A and PTEN have been demonstrated in the infants with the rare and severe form of JPS. This finding indicates a biological synergy for these genes.
- clet lip/palate
- macrocephaly and hydrocephaly
pulmonary arteriovenous malformation
colonic adenocarcinoma (cancer not arising in polyps)
cryptorchidism (undescended testes)
hereditary mixed polyposis syndrome (HMPS) (MIM.601228)
juvenile polyposis with high grade dysplasia