epithelium, and DNA markers in risk calculations

A polyposis register has been established in the Northern Region of England. A total of 48 families with 71 living affected subjects has been identified during the first three years ofoperation, a prevalence of 2*29x 1i. Indirect ophthalmoscopy identifies the majority of gene carriers by showing multiple areas of congenital hypertrophy of the retinal pigment epithelium (CHRPE). The absence of this sign in families limits its value where a relative with CHRPE has not been identified. Combining eye examination with data on age of onset and linked DNA markers is highly effective in carrier exclusion; 38% of 528 first, second, and third degree relatives had their carrier risk reduced to less than 1 in 1000. Even with such assurance many subjects will request continued bowel screening at a reduced Regional Genetics Service/Division of Human Genetics, University of Newcastle upon Tyne. J Burn, P Chapman, F Lailoo The Galton Laboratory, University College London. J Delhanty, M B Cachon-Gonzalez, K Tsioupra The Eye Infirmary, Sunderland. C Wood Division of Ophthalmology, University of Newcastle upon Tyne. W Church* Department of Surgery, Ashington Hospital, Northumberland. M Rhodest, A Gunn Correspondence to Dr Burn, Regional Genetics Advisory Service, 19 Claremont Place, Newcastle upon Tyne NE2 4AA. *Present address: Department ofOphthalmology, Aberdeen. tPresent address: Department of Surgery, University of Newcastle upon Tyne. frequency. Little interest has been shown in prenatal diagnosis. The principal value of a genetic register with domiciliary nurse visiting is the reduction in early mortality among unrecognised gene carriers. Familial adenomatous polyposis coli (FAPC) is a common autosomal dominant disorder characterised by multiple adenomatous polyps which develop, in particular, in the large bowel and show a marked propensity to malignant transformation. Following the recognition of its hereditary nature and the value of elective resection of the colon, diagnostic surgical registers began to develop. The first among these was the register at St Mark's Hospital, London where for over 50 years relatives at risk have been screened for the development of polyps by annual sigmoidoscopy. ' The potential for manifestation of the disorder up to middle age has led to the adoption of a policy of bowel examination up to the age of 50 years. When polyps develop, elective resection of the colon with ileorectal anastomosis and surveillance of the rectum2 is preferred generally to panproctocolectomy, which has the disadvantage of sphincter loss, and the ileal pouch,3 which is associated with a greater degree of surgical morbidity. Adenomata in the upper gastrointestinal tract may undergo malignant change, particularly at the ampulla of Vater.4 Desmoid tumours of the abdomen constitute a rare but major complication,5 as do the occasional development of malignancies at other sites, including thyroid papillary adenocarcinomata, central nervous system tumours, and hepatoblastomata. 8 Benign osteomata together with sebaceous cysts and intestinal polyps form the triad known as Gardner's syndrome.9 Recent molecular genetic evidence offers support to the clinical belief that Gardner's syndrome and FAPC are phenotypic variants of the same genetic Received for publication 27 July 1990. Revised version accepted for publication 19 December 1990. 289 group.bmj.com on January 6, 2018 Published by http://jmg.bmj.com/ Downloaded from