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
#Adenomatous #Polyposis #Syndromes #diagnosis #management #gastroenterology
