An unusually severe phenotype for familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a dominantly inheritedpredisposition to the development of many hundreds to thousands ofadenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age forthe development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such anextent that late sequelae such as upper gastrointestinal tumours havebecome the main cause of mortality in appropriately managedpatients. The age at which colonic surveillance begins reflects thenatural history of the disease. Onset of polyp formation and cancer inchildhood is very unusual, but has recently been associated with aspecific mutation at codon 1309 in exon 15 where a more severephenotype is sometimes observed. The case histories of two familiesare reported in which there is childhood onset of polyps in theyoungest generation and in one case a carcinoma, in whom mutations havebeen identified in exon 11 of the APC gene. Several other affectedrelatives were diagnosed at ages ranging from 5-48 years, some alreadywith a cancer at the time of first screening. Since the aim ofscreening for colonic polyps is prevention of colonic cancer, familymembers at risk should be offered genetic assessment and directmutation testing where this is possible, usually in the early teens. Inthe absence of a genetic test (the situation in about one third offamilies) or in a known gene carrier, annual colonoscopyexamination is advised from the same age. Clinicians should take noteof the family history and be prepared to consider much earlierintervention if symptoms occur in a child with a family history of FAP.Where childhood onset of polyps has occurred, other children at risk inthe family must be offered earlier genetic testing and endoscopic surveillance.