A collaborative study of the aetiology of Turner syndrome

Data on Turner Syndrome from four sources were analysed for possible associations with several aetiological factors. Two classes of liveborn propositae were included, those with a non-mosaic 45, X karyotype (XO) and those with an isochromosome of the long arm of the X (iso-X). The numbers were 288 and 84 respectively and constitute the largest series of such cases to be analysed to date. For the XO's, an analysis using the liveborn full sibs of propositae as controls (method of Carothers et al. 1978) confirmed earlier studies in finding no positive association with parental age or birth order, and even suggested a small negative association. There were no significant differences between the mean parental ages of those cases shown by Xg grouping to have received a maternal X chromosome and those of the remainder. Among the iso-X's there was an exceptionally high proportion (17.5%) of parents with an age difference (paternal-maternal) of 10 or more years, raising the possibility of a paternal age effect. This agrees with earlier studies but conflicts with the finding of a negligible tendency for affected individuals to be born later within their sibships. The apparent discrepancy may be due to the relative insensitivity of the latter method to small parental age effects in samples of this size. For the XO's there were no detectable seasonal variations in the month of birth, but for the iso-X's there was a significant excess of births in the first 6 months of the year. Reviewing the conflicting evidence from the literature on seasonal variations in chromosomal aberrations, we urge caution in interpreting these results. In agreement with earlier studies, the incidence of twins among both XO's and iso-X's was higher than the population average, but the numbers were too small for statistical significance. There was no evidence for any alteration in the sex ratio among the liveborn sibs of either class.