Table 1 Summary of adenomatous polyposis syndrome genetics, inheritance and clinical manifestation

Classical familial adenomatous polyposis

FAP

Germline APC mutations

Autosomal dominant

100–1000s colorectal polyps which manifests at age; early childhood-mid 30s (typically 16) and rapidly increasing. Almost 100% risk of CRC if left untreated.

Treatment recommendations, colectomy after adenomas emerges.

Associated with adenomatous polyps colon, CRC, fundic gland polyps, adenomatous polyps in the duodenum and periampullary region, extra intestinal lesions (fibromas, lipomas, sebaceous and epidermoid cysts = Gardner syndrome), desmoid tumours (benign soft-tissue tumours), congenital hypertrophy of the retinal pigment epithelium (CHRPE), and cancers of the brain (medulloblastoma = Turcot syndrome), pancreas, thyroid, gall bladder, bile duct and adrenal gland.

Attenuated familial adenomatous polyposis

AFAP

Germline APC mutations

Autosomal dominant

<100 colorectal polyps (typically 30) at age typically between 40 and 70 years (average 55). Estimated 70% CRC risk by age 80 years.

Treatment recommendations, colectomy may be necessary but for some polyps are limited enough in number that surveillance of colon is sufficient.

Associated with adenomatous polyps of the colon, CRC, upper gastrointestinal polyps, duodenal and gastric adenomas and fundic glad polyps. In addition, hepatoblastoma, gastric and breast adenocarcinoma have been documented.

MUTYH associated polyposis

MAP

Germline biallelic MUTYH mutations

Autosomal recessive

Usually < 100 polyps at average age of mid-50s and give a high risk of CRC.

Associated with malignancies of the duodenum, ovary, bladder and skin.

NTHL1 associated polyposis

NAP

Germline homozygous or compound heterozygous NTHL1 mutations

Autosomal recessive

Polyp number unknown as it is a recently discovered association but an extended spectrum of cancer diagnosis has been observed (CRC, endometrium, duodenum, skin, breast, pancreatic and others).

Multiple primary tumours in all patients.

Polymerase proofreading associated polyposis

PPAP

Germline POLE or POLD1 mutations

Autosomal dominant

Polyp number unknown, also recently discovered.

Associated with multi-tumour phenotypes like colon/pancreas/ovaries/small intestine and colon/ovarian/endometrial/brain.