OK, people with Klinefelter's Syndrome typically have most of their karyotype being 47,XXY and about 20% have higher order mosaicism such as 48,XXXY or 49, XXXXY. Typically, the higher order the mosaicism, the more the brain (e.g. speech) is affected. The key point to this post is the people with "most" of the karyotype being 47,XXY.
My favorite article on this, what I'm about to describe, was published in the Journal "Lancet", (p 494, 1965, Letters to the Editor, Lonsdale). While that article focused on a hermaphrodite I don't want to address that focus. I want to focus on the genetics explained in that article because that concept could have broad applicability to those identified with Klinefelter's and perhaps even some who have not been diagnosed with Klinefelter's.
In the article, the patient had the following karyotype: of 64 cells analyzed, 49 were 46,XX, 8 were 46,XY and 7 were 47,XXY. It was hypothesized that "this mosaicism could perhaps result from an initial XXY zygote with posteriorly a double mitotic loss of an X and a Y chromosome." This double mitotic loss would occur during embryogenesis. I have also seen this same explanation for other distributions in other journal articles and in one genetic textbook and I have seen several other papers on people with a similar profile in their karyotype (e.g. and more : Exp Mol Pathol. 1999 Sep;67(1):50-, although they did not include an explanation). I also noted more than one article that talked about the fact that the karyotype of different tissues could be different.
On the basis of my rather limited knowledge of genetics, I hypothesize that individuals identified as having Klinefelter's could in fact have organs that are predominantly 46,XX or 46,XY or 47,XXY and be a more or less typical female or male. However, they could something like 46,XY in the body and 46,XX in the brain (or 46,XX in the body aand 46,XY in the brain). I would liked to have talked more with a geneticist before putting this in a post but all of them that I have talked to either get rather upset at me or don't believe it would make a difference (1960 era thinking – raise someone as male and they are male). I also do not understand how a person with a 46,XX brain would develop a female brain without the requisite estrogen at the right time. On the other hand, they may actually get it by a mechanism I do not understand. That is more related to my area of research and I could look if interested. The estrogen (or testosterone) thing is a major time commitment and I got my answer to my problem so I'm no longer looking.
