Parental age and birth order in the aetiology of some sex chromosome aneuploidies.

SUMMARY The roles of maternal age, paternal age and birth order in the aetiology of the 47, XXY, 47, XXX and 47, XYY aneuploidies were examined using the liveborn full sibs of propositi as controls. As in previous studies, the incidence of XXY's and XXX's was found to be increased at high parental ages. A small but significant inverse relationship between parental age and the incidence of XYY's was also found. The results were consistent between different methods of ascertainment, different sibship sizes and different years of birth of propositi. The XXY results could not be explained without a maternal age effect and could be explained with a maternal age effect alone. The XXX and XYY results could not be explained without either a maternal or a paternal age effect, but could be explained without a birth order effect. Estimates of the relative risk at different parental ages are derived and shown to apply to the general population, provided the distribution of parental ages at birth is the same for those parents who are at risk (and who may or may not comprise the entire population) as for those who are not. The validity of the method of analysis was confirmed by applying it to a group of familial chromosome rearrangements which, as expected, revealed no dependence on parental age or birth order.