Familial Adenomatous Polyposis (FAP) Syndrome
Familial Adenomatous Polyposis Syndrome Inheritance pattern
- autosomal dominant inheritance
- APC gene is on chromosome 5q21
- APC gene plays a role in the WNT pathway in the degradation of the beta-catenin
- beta-catenin role is to turn on transcription factors in the nucleus that lead to cell cycle progression
-mutations in the APC leads to absence of b-catenin degradation and signal independent tranlocation into the nucleus where it turns on the cell cycl
Familial Adenomatous Polyposis Syndrome Clinical Presentation
- two types of clinical presentations:
Classic Familial Adenomatous Polyposis
- minimum of 100 colonic polyps
- polyps in ampulla of Vater – this leads to a prophylactic colectomy in siblings and first-degree relatives which are at risk
Attenuated Familial Adenomatous Polyposis
- patients tend to develop fewer polyps (average 30), and most of the polyps are located in the proximal colon
- lifetime risk of cancer development is usually around 50%
Gardner syndrome
- polyps identical to those in classic FAP
- multiple osteomas (particularly of the mandible, skull, and long bones)
- epidermal cysts
- fibromatosis – desmoid tumors
- less frequent are abnormalities of dentition, such as unerupted and supernumerary teeth
- higher frequency of duodenal and thyroid cancer
Turcot syndrome
- combination of adenomatous colonic polyposis and tumors of the CNS
2/3 have have APC gene mutations and develop brain medulloblastomas
- 1/3 have mutations in one of the genes associated with HNPCC and develop brain glioblastomas
Gross Features of Familial Adenomatous Polyposis
-hundreds to thousands of adenomas evenly distributed through colorectum and appendix
- adenomas range from microscopic to 1cm in diameter with larger adenomas found in the rectosigmoid
- rectum occasionally spared, especially in the attenuated FAP
- colorectal carcinomas may be multifocal
Microscopic Features of Familial Adenomatous Polyposis
- histologically identical to sporadic adenomas
- normal intervening mucosa
- adenomas evolve from single adenomatous crypts
Symptoms and Management
- patients may be asymptomatic before puberty
- initial symptoms are rectal bleeding and diarrhea
- carcinomas start about 6 years after first symptoms
- 100% colon cancer without intervention
- treatment is prophylactic total colectomy
- following colectomy, the most common cause of death is periampullary cancer in 20%