Klinefelter's syndrome in Sardinia and Scotland. Comparative studies of parental age and other aetiological factors in 47,XXY.

Data on 151 non-mosaic 47,XXY males from Sardinia, previously reported by Filippi (1986), were analysed for associations with parental ages at birth, sib order and sex ratio among siblings. The results confirm those of the earlier Scottish-based studies in that: (1) there was a significant increase in risk of 47,XXY livebirths at advanced parental ages; (2) maternal age, and maternal age alone, was sufficient to explain the effect; (3) there were no independent effects of paternal age or sib order once maternal age had been taken into account; (4) there was no evidence of any distortion of the sex ratio among siblings. Estimates of relative risk at different maternal ages were compatible with those from the Scottish studies, and pooled estimates are therefore derived. They suggest, for example, that the risk at maternal age 40 years is 2-3 times that at age 30 years. In 33 cases, the parental origin of the supernumerary X chromosome was determined by analysing the segregation of genetic markers. The mean parental ages of 19 'maternal' cases were significantly raised above those of controls, whereas those of 14 'paternal' cases were slightly, and marginally significantly, reduced. The conclusions were essentially unaffected by whether the Sardinian population, the siblings of cases or a group of 94 unrelated Sardinian males were used as controls.