AN UNUSUALLY SEVERE PHENOTYPE FOR FAMILIAL ADENOMATOUS POLYPOSIS

Familial adenomatous polyposis (FAP) is a dominantly inherited predisp osition to the development of many hundreds to thousands of adenomatou s polyps of the colon. The mean age of onset is around 15 years, sympt oms may arise in the third decade, and the median age for the developm ent of colonic cancer is 35-40 years. Prophylactic colectomy reduces t he risk of death from colorectal cancer to such an extent that late se quelae such as upper gastrointestinal tumours have become the main cau se of mortality in appropriately managed patients. The age at which co lonic surveillance begins reflects the natural history of the disease. Onset of polyp formation cancer in childhood is very unusual, but has recently been associated with a specific mutation at codon 1309 in ex on 15 where a more severe phenotype is sometimes observed. The case hi stories of two families are reported in which there is childhood onset of polyps in the youngest generation and in one case a carcinoma, in whom mutations have been identified in exon 11 of the APC gene. Severa l other affected relatives were diagnosed at ages ranging from 5-48 ye ars, some already with a cancer at the time of first screening. Since the aim of screening for colonic polyps is prevention of colonic cance r, family members at risk should be offered genetic assessment and dir ect mutation testing where this is possible, usually in the early teen s. In the absence of a genetic test (the situation in about one third of families) or in a known gene carrier, annual colonoscopy examinatio n is advised from the same age. Clinicians should take note of the fam ily history and be prepared to consider much earlier intervention if s ymptoms occur in a child with a family history of FAP. Where childhood onset of polyps has occurred, other children at risk in the family mu st be offered earlier genetic testing and endoscopic surveillance.