Familial Adenomatous Polyposis (FAP), Attenuated FAP (AFAP), Turcot Syndrome, Gardner Syndrome
APC-associated polyposis conditions result from germline mutations in the adenomatous polyposis coli (APC, OMIM# 611731) gene and cause a predisposition for colorectal cancer.1,8 APC is a tumor suppressor gene located on the long arm of chromosome 5 in band q21. Most cases of Familial adenomatous polyposis (FAP) are caused by germ-line mutations in the APC gene.1 FAP is an autosomal dominant inherited disorder characterized by hundreds to thousands of adenomatous polyps multiple polyps in the internal lining of the colon and the rectum. However, up to 30 % of FAP cases arise from new mutations in APC gene.1 Generally, polyps begin to develop during the second decade of life and 95% of individuals have polyps by age 35.1 Almost 100% of individuals who carry an APC mutation will develop colorectal cancer if treatment is not provided at early stage.1 The mean age of colorectal cancer diagnosis in untreated individuals is 35-40 years.3 FAP accounts for <1% of all colorectal cancers and it affects 1 in 8,000-10,000 individuals.1 The clinical criteria for diagnosis of FAP includes individuals that have i) more than 100 colorectal adenomatous polyps or ii) fewer than 100 colorectal adenomatous polyps and a family relative with FAP. The variants of FAP are characterized by the number of polyps or by the extracolonic manifestation. The FAP variants are attenuated FAP, Gardner syndrome, and Turcot syndrome. Attenuated FAP is characterized by presence of fewer colonic polyps (average of 30), more proximally located polyps, and diagnosis of colon cancer at a later age; however, individuals still have a high risk of developing colorectal cancer.7 AFAP is caused by germline mutations in the extreme 5′ or 3′ ends of APC or in the alternatively spliced region of exon 9,12 Gardner syndrome is characterized by colonic polyposis typical of FAP together with osteomas and soft tissue tumors such as epidermal skin cysts, fibromas, desmoid tumors.8 Turcot syndrome is characterized by the association of colonic polyposis and central nervous system (CNS) tumors (medullablastoma).5,6 Extracolonic manifestations of classical FAP and its variants may include polyps in the gastric fundus and duodenum, dental anomalies, congenital hypertrophy of the retinal pigment epithelium (CHRPE), osteomas, and other malignant changes such as thyroid tumors, small bowl cancer, hepatoblastoma, and brain tumor.1,4, 9
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APC Gene Mutation Analysis Assay Summary
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- Fearnhead NS et al. Human Mol. Genet. 2001; 10:721–733.