Table 5.

Disorders to Consider in the Differential Diagnosis of MUTYH Polyposis

Cancer Susceptibility SyndromeGene(s) /
Genetic
Mechanism		MOIPolyps /
Colon Cancer		Associated
Malignancies		Other Features /
Comments
APC-associated polyposis conditions APC ADAttenuated FAP:
  • 0-100 colonic polyps
  • CRC risk: 70%
FAP:
  • 100 colonic polyps
  • Upper GI polyps
  • CRC risk: 100%
  • Small bowel
  • Pancreatic
  • Thyroid
  • Liver
  • Brain
  • Bile duct
  • Gastric
  • CHRPE
  • Osteomas
  • Supernumerary or missing teeth
  • Cutaneous lesions
  • Desmoid tumors
NTHL1-associated polyposis NTHL1 AR
  • 8-50 adenomatous colonic polyps
  • Duodenal adenomas
  • CRC in 16/29 individuals
Extracolonic cancer in 12/29 individuals:
  • Uterine
  • Duodenal
  • Breast
  • Premalignant endometrial lesions
  • 2nd most common AR form of colon cancer & polyps after MAP 1
Lynch syndrome
(hereditary non-polyposis colon cancer)		 MLH1
MSH2
MSH6
PMS2
EPCAM 		AD
  • 4% develop ≥10 polyps
  • Colon tumors often MSI+
  • CRC risk: 52%-82%
  • Uterine
  • Ovarian
  • Small bowel
  • Gastric
  • Urinary tract
  • Skin
  • Brain
  • Hepatobiliary tract
  • Pancreas
  • Prostate
Peutz-Jeghers syndrome STK11 AD
  • GI hamartomatous polyps
  • Polyps most often in small bowel
  • Adenomatous colonic polyps can occur.
  • CRC risk: 39%
  • Gastric
  • Breast
  • Ovarian
  • Small bowel
  • Pancreas
  • Cervix
  • Uterine
  • Lung
  • Testicular
  • Ovarian sex cord tumors w/annular tubules
  • Dk-brown to dk-blue melanocytic macules (fade w/age)
Juvenile polyposis syndrome BMPR1A
SMAD4 		AD
  • Hamartomatous (juvenile) polyps in small bowel, stomach, colon, & rectum
  • CRC risk: 38.7%
  • Gastric
  • Upper GI tract
  • Pancreas
Hereditary hemorrhagic telangiectasia (SMAD4-related)
PTEN hamartoma tumor syndrome PTEN AD
  • Multiple hamartomatous & mixed polyps in GI tract
  • CRC risk: 9%
  • Breast
  • Thyroid
  • Uterine
  • Renal
  • Brain
  • Melanoma
  • Thyroid disease/nodules
  • Uterine fibroids
  • Macrocephaly
  • Lipomas
  • Mucocutaneous lesions
  • Pigmented macules of glans penis
  • Hamartomatous overgrowth of tissues
  • Connective tissue nevi
  • Epidermal nevi
  • Hyperostoses
Hereditary mixed polyposis syndrome (OMIM 610069, 601228)BMPR1A
GREM1
dup 15q13-q14 2		AD
  • Adenomatous polyps, juvenile polyps, hyperplastic polyps, & polyps containing mixed histology
  • ↑ CRC risk 3
Desmoid tumor, prostate cancer, & duodenal adenocarcinoma reported in 1 individual 4Rare condition (few families)
Sessile serrated polyposis syndrome
(OMIM 617108)		 RNF43 AD
  • Sessile serrated polyps, serrated adenomas, or hyperplastic polyps of GI tract
  • CRC risk: ≤54%
Unknown (various cancers reported in untested family members)Rare condition (few individuals)

AD = autosomal dominant; AR = autosomal recessive; CHRPE = congenital hypertrophy of the retinal pigment epithelium; CRC = colorectal cancer; FAP = familial adenomatous polyposis; MAP = MUTYH polyposis; MOI = mode of inheritance; MSI = microsatellite instability

1.
2.

Leads to overexpression of GREM1

3.
4.

From: MUTYH Polyposis

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