Presentation: Person with a family history of polyposis

A 39-year-old asymptomatic male attended gastroenterology clinic to discuss his risk of colorectal cancer and the need for surveillance, following the recent diagnosis of serrated polyposis syndrome (SPS) in his brother.

• The presence of a family history of SPS or multiple colorectal adenomas (MCRAs) does not meet eligibility criteria for genomic testing in the National Genomic Test Directory, owing to the lack of identified pathogenic causative gene variants.
• However, first-degree relatives of patients with a genetic diagnosis of polyposis syndromes (including familial adenomatous polyposis, Peutz-Jeghers syndrome or juvenile polyposis syndrome) should be offered routine predictive testing by clinical genetics.

• This topic covers management of first-degree relatives of a patient with polyposis. For non-polyposis colorectal cancer, see Presentation: Patient with a family history suggestive of Lynch syndrome.
• A reported family history of SPS or MCRA polyposis should be verified by review of histopathology and/or endoscopy reports to confirm presence of 10 or more adenomas or serrated lesions in a first-degree relatives.
• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For predictive testing of a first-degree relative of a patient with polyposis syndrome and an identified pathogenic variant, usually this testing is performed by clinical genetics, and the appropriate panel to choose is:
  • R242 Predictive testing for known familial mutation(s): This is a targeted variant test that will determine whether the relative has the familial pathogenic variant. No other polyposis related syndromes genes are tested.
• For tests such as R242, which do not include whole genome sequencing, you can use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
  • As it is a predictive test, appropriate genetic counselling should be provided and further management options such cascade testing for other at-risk relatives and pre-implantation genetic diagnosis can be discussed.
• Below are the surveillance recommendations for first-degree relatives of patients with the named condition.
• Serrated polyposis syndrome (meeting updated WHO 2019 diagnostic criteria):
  • colonoscopy once every 5 years from either 40 years of age or 10 years earlier than index case, to 75 years of age.
• Multiple colorectal adenomas:
  • colonoscopy can be considered at time of index case diagnosis and/or at 50 years old, to identify the phenotype of high penetrance cancer predisposition syndromes.
• Familial adenomatous polyposis (FAP):
  • predictive genomic testing is offered as routine;
  • if a carrier of an APC pathogenic variant, then:
    • colonoscopy every one to three years (depending on phenotype) starting from 12–14 years of age;
    • upper gastrointestinal endoscopy from 25 years of age, with frequency being dependent on the Spigelman criteria.
  • if no identified constitutional (germline) pathogenic variant, then:
    • colonoscopy once every five years from 12–14 years old until of national screening age;
    • upper gastrointestinal endoscopy only required if a clinical diagnosis of colorectal polyposis syndrome is made.
• Peutz-Jeghers syndrome (PJS):
  • offer predictive genomic testing to children (ideally before onset of symptoms);
  • where a clinical, but not a molecular diagnosis, of PJS then you should offer upper gastrointestinal endoscopy, colonoscopy and video capsule endoscopy at 8 years old.
• Juvenile polyposis syndrome (JPS):
  • offer predictive genomic testing between 12–14 years old (or earlier if symptomatic);
  • where a clinical, but not molecular diagnosis, of JPS, then you should offer colonoscopy once every five years from 15 years old. An upper gastrointestinal endoscopy is not required unless colonic JPS is detected, or if there is a family history or hereditary haemorrhagic telangiectasia.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• UK Cancer Genetics Group: UKCGG leaflets and guidelines – see:
  • APC: ‘Management guidelines for carriers of pathogenic variants APC’
  • Juvenile Polyposis: ‘Management guidelines for BMPR1A pathogenic variant carriers’ and ‘Management guidelines for SMAD4 pathogenic variant carriers’

References:

• Clark S, Cuthill V, Hawkins J and others. ‘Hereditary gastrointestinal polyposis syndromes Rare Disease Collaborative Network consensus statement agreed at the RDCN meeting Birmingham 17th February 2022‘. BJC Reports 2023: volume 1, article number 10. DOI: 10.1038/s44276-023-00011-z
• Monahan KJ, Bradshaw N, Dolwani S and others. ‘Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)‘. Gut 2020: volume 69, issue 3, pages 411–444. DOI: 10.1136/gutjnl-2019-319915

For patients

• Cancer Research UK: Screening for people at high risk of bowel cancer
• St Mark’s Hospital: Polyposis Patient Information