Description
Multiple bowel polyps eligibility statement:

Multiple bowel polyps inclusion criteria (30616)
FAMILIAL ADENOMAS:
•	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

JUVENILE POLYPOSIS:
•	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.

Multiple bowel polyps exclusion criteria (30616)

Prior genetic testing guidance (30616)
- 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.

Multiple bowel polyps prior genetic testing genes (30616)
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)

Closing statement (30616)
These requirements will be kept under continual review during the main programme and may be subject to change.

3 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Ian Frayling (Cardiff University)

    Group: GeCIP domain
    Workplace: NHS diagnostic lab

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

14 genes

13 reviewed, 12 green

List Gene Reviews Mode of inheritance Details
14 genes
Green Green List (high evidence)
APC
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Emory Genetics Laboratory
Phenotypes
  • APC-Associated Polyposis Disorders
  • Familial Adenomatous Polyposis
  • Familial Adenomatous Polyposis 1
Green Green List (high evidence)
BMPR1A
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Polyposis, juvenile intestinal, 174900
  • Polyposis syndrome, hereditary mixed, 2, 610069
  • Juvenile polyposis syndrome, infantile form, 174900
  • Juvenile Polyposis Syndrome
  • juvenile polyposis
Green Green List (high evidence)
MLH1
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Green Green List (high evidence)
MSH2
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
Green Green List (high evidence)
MSH6
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
Green Green List (high evidence)
MUTYH
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • MYH-Associated Polyposis
  • MUTYH-Associated Polyposis
  • Familial Adenomatous Polyposis, 2
  • adenomatous polyposis
Green Green List (high evidence)
NTHL1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Multiple colorectal adenomas
  • colorectal cancer
Green Green List (high evidence)
PMS2
1 review
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Lynch syndrome
Green Green List (high evidence)
POLD1
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Familial polyposis and colon cancer
Green Green List (high evidence)
POLE
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Familial polyposis and colon cancer
Green Green List (high evidence)
PTEN
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Bowel polyps found in majority of patients with PTEN-related disorders
Green Green List (high evidence)
SMAD4
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Pancreatic cancer
  • Polyposis, juvenile intestinal, 174900
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
  • Myhre syndrome, 139210
  • Juvenile Polyposis Syndrome
  • juvenile polyposis
Red Red List (low evidence)
ENG
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Juvenile Polyposis
Red Red List (low evidence)
GREM1
2 reviews
1 green
Not set
Sources
  • Expert Review Red
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Colorectal cancer, increased risk, association with}(Peters (2012) Hum Genet 131,217)
  • Oligosyndactyly of the hands, Cenani-Linz-like (Dimitrov (2010) J Med Genet 47,569)
  • Mixed polyposis syndrome (Jaeger (2012) Nat Genet 44,699)
  • Polyposis Syndrome, Hereditary Mixed, 1
  • Hereditary Mixed Polyposis Syndrome

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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