Adenomatous Polyposis Syndromes:  Familial Adenomatous Polyposis (FAP), Attenuated FAP (AFAP), MUTYH associated polyposis (MAP)
✓ Genetic test if > 10 cumulative adenoma, typical extra-colonic features, or relative of known index patient

Familial Adenomatous Polyposis (FAP):
 - "CRC + Duodenal (ampullary!) + Thyroid + Breast *FAP"
 - Autosomal Dominant; close to 100% penetrant
 - >100 synchronous colorectal adenomas
 → 100% CRC risk if left untreated
 → Appear in 2nd or 3rd decade (mean 15.9), slight distal > proximal
 → Most < 1cm, mostly tubular adenoma w/o villous features
 → Unique histology: "Microadenomas" = dysplastic or adenomatous cells in single crypts or portions of crypts. Can be in normal tissue.
 - Germline APC mutation on chr5. APC is tumor suppressor. Inherit one damaged allele; other allele damaged over time
 → Location of mutation on gene → phenotype, extracolonic features
 - Variants:
     → Turcot Syndrome: FAP + Brain tumors (glioma, medulloblastoma).
     → Gardner syndrome: FAP + Osteomas, desmoids, fibromas, epidermoid cysts, sebaceous cysts, supernumerary teeth, congenital hypertrophy of retinal pigment

Attenuated FAP (AFAP):
 - "mild, later onset FAP" 
 - Autosomal Dominant
 - 10-100 adenomas
 - APC Mutation in proximal or distal end of gene
 - Polyps 10-20 years later than FAP
 → Proximal > Distal compared to FAP, relative rectal sparing
 - May never need colectomy if can be controlled endoscopically
 → Surgery = IRA (rectal sparing)

MUTYH associated polyposis (MAP):
 - "Adenomas, Recessive", Autosomal Recessive
 - 20-99 adenomas, can have > 100
 - CRC median age 48-53
 - Biallelic MUTYH mutation (monoallelic ? Slight ↑ CRC)
 → proximal or distal, relative rectal sparing
 → Base excision repair gene; protein for DNA oxidative damage repair. Failure of gen → mutations in key genes (APC, KRAS, etc).

Dean Ehrlich MD @DeanEhrlich_MD

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