Polyposis syndromes

Adenomatous polyposis syndromes

What are adenomatous polyposis syndromes?

Adenomatous polyposis syndromes are the most common form of polyposis and characterised by the occurrence of dozens to thousands of adenomas (i.e. polyps of a certain type) mainly in the large bowel, but also in the upper gastrointestinal tract. If not detected early and removed, some polyps will invariably result in colorectal cancer. The minimum number of adenomas to diagnose an adenomatous polyposis is not clearly defined and also depends on the localisation, the age at onset, and family history, however, at least ten confirmed colorectal adenomas are usually required.

Currently, at least five different inherited forms of adenomatous polyposis, caused by genetic changes (germline mutations) in six different genes, can be identified (see below). Although all types are defined by the presence of multiple colorectal adenomas which result in a similar diagnostic and therapeutic approach, a marked clinical variability concerning the number of polyps and age at onset can be observed, even within families. In addition, the upper gastrointestinal tract is frequently affected and most forms are accompanied by a spectrum of benign and malignant tumours outside the gastrointestinal tract.

What are the genetic causes of adenomatous polyposis syndromes?

The inherited forms of adenomatous polyposes are caused by genetic errors (mutations) that are usually transmitted from one or both parents and thus are present in all cells of the body (germline mutations). The causative genes are usually responsible for the correction of DNA errors (DNA repair genes) or the suppression of cell growth and proliferation (tumour suppressor genes).

Depending on the underlying affected gene, the condition is named in a different way (some types include already the gene name). The Familial adenomatous polyposis (FAP) is the most common and best known form, which is caused by germline mutations of the APC gene. The second most frequent type of adenomatous polyposis is the MUTYH-associated polyposis (MAP). All the other conditions such as the Polymerase Proofreading associated polyposis (PPAP, caused by germline mutations in the genes POLE or POLD1), the NTHL1-associated polyposis (NAP), and the MSH3-associated polyposis, are very rare and have been identified in recent years, so that the characterisation of the full spectrum and risk of tumours has not been finished yet. However, also in patients, where no genetic cause can be identified with current methods, a hereditary basis is likely.

How are adenomatous polyposis syndromes inherited?

In conditions such as FAP or PPAP only one of the two copies of the gene is affected. Children of an affected mother or father are at a 50% risk of inheriting the mutation and therefore the increased tumour risk (autosomal dominant mode of inheritance). If a child does not inherit the mutation, she or he will not develop the disease. Typically, there can be multiple affected individuals throughout many generations in a family. However, it is also possible that the mutation originate in the affected individual for the first time.

In contrast, in conditions such as MAP, NAP, or the MSH3-associated polyposis both copies of the gene are mutated. Siblings of an affected individual are at a 25% recurrence risk while the parents and children are usually not affected (autosomal recessive mode of inheritance). As a consequence, the disease is characterized by a single affected individual in a family or affected individuals in a sibship.

What are the surveillance / preventive options?

Affected individuals as well as all family members in whom the genetic defect has been detected or who are at risk of having inherited the disorder and have not been tested yet should undergo established intense surveillance / cancer prevention programs. The spectrum, frequency, and onset of the different surveillance examinations depend on the underlying condition and clinical presentation. Appropriate measures may include endoscopic examinations and imaging as well as preventive medical and surgical treatment.

The most important and effective surveillance measure in all adenomatous polyposis syndromes are frequent colonoscopies and endoscopic examinations of the upper gastrointestinal tract. In case of high polyp numbers, a colectomy (that is the complete or partial removal of the large bowel) must be considered. In some cases, preventive medical options are available. In some conditions, the programme starts during childhood already, in more late-onset (attenuated) conditions around 18 - 20 years of age. For individuals with very rare and recently identified conditions such as PAPP and NAP, no specific surveillance programmes exist so far; the applied surveillance examinations follow the recommendations for the established conditions (FAP, MAP).


Hamartomatous and other polyposis syndromes

Juvenile polyposis syndrome consists of hundreds of juvenile polyps. Presentation in the second decade is most common. Rectal bleeding, bowel obstruction and intussusception are common presentations.

Both the tumour suppressor gene SMAD4 on chromosome 10q (50% of cases) and BMPR1A gene have been implicated. The genetic basis is not always known.

Peutz-Jeghers syndrome has an autosomal dominant inheritance and is characterised by:

  • multiple hamartomatous polyps, most commonly involving the small intestine (predominantly the ileum), but also colon and stomach; mouth and oesophagus are spared
  • mucocutaneous melanin pigmentation involving the mouth, fingers and toes

Serrated Polyposis Syndrome (SPS) is a syndrome in which multiple hyperplastic or serrated polyps are identified in the large bowel.


Clinical practice guidelines

Endorsed by ERN GENTURIS*

Adenomatous polyposis syndromes:

Hamartomatous and other polyposis syndromes:

Hereditary colorectal cancer:

* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.


ERN GENTURIS care pathway

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ERN GENTURIS patient journey

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ERN GENTURIS publications

Thematic Group 2: Lynch syndrome and polyposis

Adenomatous polyposis syndromes

Hamartomatous and other polyposis syndromes


ERN GENTURIS healthcare providers

A list of healthcare providers with expertise in Thematic Group 2: Lynch syndrome and polyposis can be found here.


Patient associations for hereditary cancer syndromes

A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.