Sex Ratio in Down Syndrome

Data from 55 publications providing the sex ratio (SR), i.e. ratio between male and female cases of Down syndrome (DS), are presented. In general, SR was skewed toward an excess of males in the majority of studied populations, either in populations with a high level of cases ascertainment (epidemiological studies) or in selected groups. No significant correlation involving the age of either patients or mothers was found. Some other factors which might influence the sex ratio in DS at birth are mentioned. Meta-analysis of data from epidemiological studies suggests the phenomenon is not restricted to free trisomy 21alone but appears in translocation cases, both in mutant and inherited translocation carriers (SR=1.31 and 1.36, respectively). In contrast to nonmosaic 47+21 cases, where SR is close to 1.3, an excess of females was observed in mosaics 46/47+21(SR=0.83). No male predominance was found among patients with DS not tested cytogenetically (SR=0.98), which may be explained by female predominance in false-positive cases. In populations with a fraction of clinically diagnosed cases of 30% and over, SR has intermediate value of 1.1. The ratio showed a tendency to increase with time since 1940's, reaching a mean value of 1.35 in 1980's (1.3–1.62 in different populations), which might be a consequence of the growing use of karyotyping to confirm diagnosis and by an increase in proportion of males in confirmed cases. In the 1990's the ratio fell to 1.22 (1.03–1.27). As SR is assumed to reflect a proportion of paternal contribution, the discrepancy between the proportions of paternal errors in cytogenetic and molecular studies discussed in the literature might be explained by temporal changes. Genetic mechanisms of male predominance in trisomy 21 are reviewed, among them models for joint segregation of chromosome 21 and Y chromosome in spermatogenesis, and the chromosome 21 nondisjunction during 2nd meiotic division of oogenesis caused by Y chromosome-bearing spermatozoa.

Keywords: