Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature.

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 were evaluated and categorized. Attenuated FAP (AFAP, <100 colorectal adenomas) is correlated with mutations before codon 157, after codon 1595 and in the alternatively spliced region of exon 9. Severe polyposis (>1000 adenomas) is found in patients with mutations between codons 1250 and 1464. Mutations in the remainder of the APC gene cause an intermediate phenotype (hundred to thousands of adenomas). Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and desmoid tumours are associated with mutations between codons 311 and 1444 and after codon 1444, respectively. No consistent correlations were found for upper gastrointestinal tumours. Genotype-phenotype correlations in FAP will be useful in decisions concerning screening and surgical management of FAP.