Table 2 Diagnostic criteria

Peutz-Jeghers Syndrome

(1) Two or more histologically confirmed PJS-type hamartomatous polyps,

or

(2) Any number of PJS-type polyps detected in an individual, who has a family history of PJS in (a) close relative(s)

or

(3) Characteristic mucocutaneous pigmentations in an individual, who has a family history of PJS in a close relative(s)

or

(4) Any number of PJS-type polyps in an individual who also has characteristic mucocutaneous pigmentations

Juvenile Polyposis Syndrome

(1) More than five juvenile polyps in the colorectum

or

(2) Multiple juvenile polyps throughout the GI-tract

or

(3) Any number of juvenile polyps and a family history of JPS

POLE-associated polyposis

Heterozygosity for a pathogenic missense variant in the exonuclease domain (exon 9–14) of POLE, especially p.Leu424Val (Biallelic truncating/splice variants is associated with IMAGe syndrome (MIM: 614732)) and FILS syndrome (MIM: 615139))

POLD1-associated polyposis

Heterozygosity for a pathogenic missense variant in the exonuclease domain (exons 6–12) of POLD1

AXIN2-associated polyposis

Heterozygosity for a pathogenic variant in AXIN2, especially in exon 8

MUTYH- NTHL1-MSH3- or MLH3-associated polyposis

Biallelic pathogenic variants in the relevant gene (MUTYH, NTHL1, MSH3, MLH3,)

Constitutional mismatch repair deficiency syndrome

Biallelic pathogenic variants in an MMR gene (MLH1, MSH2, MSH6, and PMS2, mainly PMS2. Biallelic carriers of highly penetrant variants are not viable and will die before birth

GREM1-associated mixed polyposis

Heterozygosity for a duplication upstream of GREM1

Serrated Polyposis Syndrome

(1) At least five serrated lesions/polyps proximal to the rectum, all being 5 or more mm in size with two or more being at least 10 mm in size.

(2) More than 20 serrated lesions/polyps of any size distributed throughout the large bowel, with at least five being proximal to the rectum.

Polyposis with unknown etiology

(1) At least one family member has had from 20 to 30 (dependent on age) to 99* colorectal polyps, and

(2) screening of the relevant genes has not detected a pathogenic variant that can explain the family history, and

(3) no other etiology to the gastrointestinal polyps/cancers observed in the family (e.g. genetic syndromes, inflammatory bowel disease etc.) is likely

Furthermore, a family history with a significant occurrence of colorectal adenomas/polyps in two or more relatives can indicate a clinically significant predisposition.

*If the patient or a relative has had over 100 polyps, the guidelines for FAP should be used