- proband affected with >10 adenomatous polyps (all diagnosed age <50) AND first degree-relative affected by >10 adenomatous polyps (all diagnosed age <50) AND
- >=3 adenomas have been histologically confirmed in each of proband and affected first degree relative
- Samples should be available and obtainable from proband AND affected first degree-relative
- Samples may also be obtained from any additional affected first/second degree-relatives with > 5 adenomatous polyps (all diagnosed age <50)
- Note: Adenomas can be synchronous OR metachronous
- Presumed inheritance model: dominant
ISOLATED (PRESUMED RECESSIVE) POLYPOSIS:
- Proband affected with:
– (a) >25 polyps (all diagnosed age <50) OR
– (b) >10 polyps (all diagnosed age <25) OR
– (c) >10 polyps (all diagnosed age <40 and parents consanguineous)
- Samples should be obtained on proband
- Samples may also be obtained for any additional family members affected with >10 polyps (all diagnosed age <50)
- Where samples can be obtained from both parents, they should be sought.
- Note: Polyps can be synchronous OR metachronous. Polyps can include adenomas, hyperplastic polyps or serrated polyps. Polyp histology should be detailed in clinical data model
- Presumed inheritance model: recessive or de novo
- Proband affected with >2 juvenile polyps AND >=2 juvenile polyps have been histologically confirmed in proband
- Samples should be obtained on proband AND both parents
- Samples may be obtained on any additional family members affected with juvenile polyposis
- Note: Juvenile polyps can arise anywhere in the GI tract
Unaffected individuals should not be recruited in this disorder (with the exception of parents in recessive and juvenile polyposis). Recruitment should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.
Prior genetic testing guidance
– Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
– Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.
PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Prior genetic testing genes
Testing as below is strongly recommended PRIOR TO RECRUITMENT to allow appropriate management of families with readily detectable mutations in known disease genes:
- APC, biallelic mutations in MUTYH (familial adenomas)
- APC, biallelic mutations in MUTYH, MLH1, MSH2, MSH6 (isolated polyposis)
- SMAD4, BMPR1A (juvenile polyposis)
These requirements will be kept under continual review during the main programme and may be subject to change.« Back to Disease List