Genotype-phenotype Correlations In Familial Adenomatous Polyposis

Mutations in the adenomatous polyposis coli (APC) gene cause familial adenomatous polyposis (FAP). Disease severity and the presence of extracolonic manifestations seem to be correlated with the location of the mutation on the APC gene. In this review, large studies describing genotype-phenotype correlations in FAP during the past20years were evaluated and categorized. Attenuated FAP (AFAP,<100colorectal adenomas) is correlated with mutations at the3’end, the5’end and within the alternatively spliced region of exon9. Profuse polyposis (>1000adenomas) is found in patients with mutations within or near the mutation cluster region (MCR). Mutations in the remainder of the APC gene cause an intermediate phenotype (100-1000adenomas). Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and desmoid tumors are associated with mutations between codons311and1445and after codon1260, respectively. No consistent correlations were found for upper gastrointestinal polyps. Papillary thyroid carcinoma, osteoma and CNS tumors have shown the correlations. Genotype-phenotype correlations in FAP have important implications for genetic counseling, family surveillance and treatment decisions of FAP.