The Importance of Familial Clusterings in Crohn’s Disease

Dr. H. J. Van Kruiningen’s present address is Department of Pathobiology, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089, U.S.A. E-mail: [email protected] Disease clustering is prevalent today. Patients and the public are concerned when multiple cases of a disease occur in close proximity to one another, and the scientific community usually takes notice. Clusterings of the past have sometimes been shown to have a genetic basis (1) and at others to have been of environmental or infectious etiology (2,–4). Diseases of unknown etiology—including Crohn’s disease (CD)—hold our greatest interest. Any discussion of familial clusterings of CD includes two levels of consideration: Are there instances of multiple cases of Crohn’s disease within families and, if so, what do we make of that? And, if such families exist, is there a geographic distribution for them that perhaps can contribute to our understanding of the disease? Multiple cases of CD within families have certainly been documented (5,–11). Why do multiple cases in families occur? Statisticians point out that a few clusterings within families must occur by chance alone. However in the case of CD and in instances of CD and ulcerative colitis (UC) in the same family, the numbers make it clear that this is more than a coincidence. There are too many families, large and small, affected with multiple cases. A second explanation sometimes offered is that there is “maternal anticipation” for that second or third case in a family, coupled with a zealousness on the part of research clinicians in particular referral centers. Even the most objective of clinicians cannot assure parents that there is no need to anticipate disease in another family member. Having a family member with CD is, after all, the strongest risk factor (12). The number of affected relatives within a family may vary according to diagnostic criteria. Not all the diagnoses have been confirmed by examination of resected specimens. Although there may be an element of subjectivity in defining multiple-case families, there are many familial aggregations that have been recognized by sound clinical, imaging, and endoscopic features, with or without surgery, that warrant study (9,–12).