A disorder for which identical twins are not completely concordant must be caused, at least in part, by environmental factors. Acute childhood leukemia is such a disorder, with concordance ratios as follows: approximately 1:5 for monozygotic twins, approximately 1:80 for dizygotic twins, and more than 1:500 for ordinary siblings.
Of all malignancies, only acute childhood leukemia carries such an extraordinary risk of twin concordance. It is the only childhood malignancy in which a large number of circulating malignant cells are found. In most instances, twins with concordant leukemia have their onset of illness within weeks or months of each other, suggesting a similar inciting event. Since placental cross-circulation is found commonly in monozygotic twins and occasionally in dizygotic twins, cross-infusion of malignant cells has been postulated to account for the high twin concordance ratios. Leukemia in most twins might then represent only one occurrence of leukemia and not two.
This hypothesis, while consistent with most observations, does not explain the pattern of disease in the twins described in this paper. Our proband became ill at nearly 6 years of age, and her twin's illness occurred more than 6 years later. These twins probably remained at risk of concordant disease because of postnatal factors affecting predisposed siblings. Whether the predisposition was due to genetic or to prenatal environmental factors remains unknown.
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