We were very interested to read the recent article published by Morris et al1 suggesting that the prevalence of Klinefelter syndrome (KS), XXY, may be increasing. We are currently carrying out analyses using routinely collected data in Victoria to ascertain an estimate of XXY prevalence in Australia. Studies like these highlight the value in systematic collection of various types of information for public health purposes. Certainly, preliminary analysis of our more recent data (unpublished) suggests a higher prenatal prevalence than has been previously indicated in prenatal studies extending back to 1970.2

By separating the earlier and later newborn chromosome surveys, Morris et al showed a difference in prevalence of XXY between the two time periods. However, although all three sex trisomies were seen at similar frequencies in the earlier surveys, neither the prevalence of XYY nor XXX changed in the later surveys. The observed increase in the frequency of XXY was supported by data series of prenatal diagnoses, spontaneous abortions and perinatal deaths.

On the basis of this finding, the authors hypothesise that the increase in frequency of XXY is due to an increase in non-disjunction at paternal meiosis I, and that this may be caused by the same factors that have been attributed to the falling sperm counts in men. Such factors may include prenatal exposure to environmental chemicals or perinatal exposure to known environmental xeno-oestrogens.3

The effect of maternal age on KS is well established but would cause a similar increase in the frequency of XXX, which was not seen by Morris et al. However, the authors do not mention paternal age effect as a possible explanation, or at least contributing factor, for the increase in the frequency of XXY conceptions. Increasing paternal age trends in Australia are similar to those seen in the United Kingdom, with the average age of fathers of live births reaching an all time high of 33.1 years in 2006 years, and the number of men in their 50s having children up by around 20% in the last decade.4

The effect of paternal age on recombination frequency (reduced in XY disomic sperm) and non-disjunction is a controversial area, with not all study findings supporting a relationship, yet there remains a substantial body of evidence that indicates an association between paternal age and the birth of a child with KS.5 If the increased frequency of XXY that has been observed is due to a paternal age effect acting only at meiosis I, this would explain the lack of corresponding increases in frequencies of XYY and XXX.

Finally, we are curious about the lack of reference to the comprehensive study of Bojesen et al2 in 2003 that utilised the extensive prenatal and postnatal diagnoses Danish databases, and covers a considerable time period. We presume that this was excluded because it only considered karyotypes associated with KS and not the other two sex chromosome trisomies. However, in our organisation, we use this publication as our benchmark for KS prevalence, and would be interested to hear the perspective of Morris et al on how this study compares to theirs in regards to the prevalence of KS.

Above all else, the possible increasing frequency of XXY only further highlights the need for increased awareness and detection of males with the condition at an age and stage of development most appropriate for treatment and intervention. The best time to be diagnosed has yet to be determined and there remains a lack of research on the psychosocial impacts of having KS, and how quality of life and life outcomes might be affected by age of diagnosis. If this condition is truly becoming even more common, it is vital that we identify the needs of this group of males.