Familial Crohn's disease in single or multiple first-degree relatives

The strongest currently recognized risk factor for Crohn's disease (CD) development is having a relative with the disease. In this study, 1,000 patients with CD, seen directly by the investigator during a period of more than 20 years, were consecutively evaluated for a family history of CD. There were 140 patients who reported a relative with CD. Of these, all 87 first-degree relatives were confirmed to have CD (36 men and 51 women). Siblings, particularly women, were most commonly affected in comparison with parents or children. There were 65 with a single affected first-degree relative and 22 with multiple affected first-degree relatives. In this series, the tendency to have a female sibling with CD was further increased in those with multiple affected first-degree relatives. Although the age of diagnosis of children was less than the age of diagnosis in the respective parents, there were almost identical numbers of mother-child and father-child pairs. These findings in a population with prolonged follow-up by the same physician may reflect a bias toward case ascertainment rather than the previously reported phenomena in recruited populations of genetic anticipation and genomic imprinting. Patients with multiple first-degree relatives were older with more extensive disease in both ileal and colonic sites compared with those with only a single first-degree relative and more frequent colonic disease. Future studies are needed to further explore the role of both genetic and environmental factors in the pathogenesis and phenotypic expression of familial CD.