Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent

Abstract

Background - Genetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn's disease in affected parents and offspring. Aims - To compare affected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect. Methods - 137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records. Results - Of the 137 affected parent-child pairs, 50 had Crohn's disease only, 51 had ulcerative colitis only, and in 36, one had Crohn's disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn's disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age differences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an effect of parental sex on age at diagnosis or disease extent in offspring. Conclusions - There was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.