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 diVerences at diagnosis of Crohn's disease in aVected parents and oVspring. Aims-To compare aVected 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 eVect. Methods-137 aVected 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 aVected 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 diVerences 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 eVect of parental sex on age at diagnosis or disease extent in oVspring. 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 diVerences at diagnosis between aVected parents and children. (Gut 1999;44:808-811)

Clinical presentation of Crohn's disease: association between familial disease, smoking, disease phenotype, extraintestinal manifestations and need for surgery

“…However, in concordance with more recent studies (45,46), our results suggested that anticipation does not occur in IBD. In this study, we could not prove an earlier age at onset, or a difference in disease location, behavior or increased need for aggressive immunosuppressive therapy and surgery in patients with familial disease compared to sporadic patients with identical disease duration and similar smoking habits.…”

“…In our study ileal disease and most markedly The coefficient is equivalent to the natural log of the odds ratio (OR). non-inflammatory behavior were associated with increased risk for surgery and, in concordance with data in patients from Israel (45,46), no differences were found in the need for operation or for immunosuppressants between smokers and non-smokers. Of note, in the study of Cosnes et al immunosuppressive therapy was suggested to neutralize the effect of smoking on the need for surgery (43).…”

Crohn's Disease: current state of biological therapy

“…Genetic aspects involving CD have been known since the past century, usually due to epidemiological studies addressed to etiological and pathogenetic factors [36][37][38][39][40] . However, the genetic perspective was only established after the first gene related to CD was described 41 , and successfully confirmed [42][43][44] .…”

Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

“…Although no sex difference exists in sporadic or familial IBD [35,36], linkage to the X chromosome was found twice [37,38]. Moreover, an increase in maternal transmission was shown in non-Jewish parent-child pairs [39], which was also described in mixed UC/CD families [40]. Whether this sex bias is caused by true genetic association or by imprinting of the X chromosome is not clear.…”