46,XX Karyotype: Disorders

00:01 Now, let’s consider disorders associated with an XX karyotype. Chromosomally, the individual is XX but it may not come out there phenotypically. Most of all, as you would expect, we will see that there is a translocation of the SRY gene from the Y chromosome and onto the X chromosome.

00:27 If the X chromosome has an SRY gene just as we would expect from normal sexual development, the primordial gonad will become a testis because there’s the SRY gene being expressed as testis determining factor. We will see development of testis and ideally testosterone and then production of male external genitalia. In the cases where we have an SRY gene, generally everything proceeds as normal male sexual development. However, we call them XX testicular DSD's because we see that there are testes developing. Now, there are some cases where we don’t see an SRY gene present at all. So, it wasn’t translocated from the Y chromosome to the X chromosome. We essentially have two normal X chromosomes. Some of these patients have ambiguous genitalia that suggest evidence of male sexual development. But how is that even possible when there’s no SRY gene? That’s a really great question, a pretty active field of research presently.

01:46 But the evidence that we see is that even though the genitalia may be ambiguous, they have cryptorchidism. So, there are definitely testes but they’re undescended or hypospadias in which the urethra hasn’t made its way all the way through the penis. So, it’s located just below the penis and it’s just not normal. Male development looks ambiguous. One of those who knows what. Another condition we see, even smaller percentage, will have both testicular and ovarian tissues. So, this is where we might answer the question about true hermaphroditism because surely if you have one ovary and one testis, it sort of looks hermaphroditic.

02:34 But the problem there is that we actually as humans, as you know cannot reproduce with our self in order to have one offspring where you self-fertilize. Leave that for other organisms.

02:51 But it’s completely possible that we have the gonad, the one and the other on the other side or you could have an ovotestis which the testis is made up of both ovarian and testicular tissue.

03:09 Another means that could help this happen. So, there are a couple of different things that could be going on. As I said, there’s a lot of research going on to how does this not SRY gene XX karyotype have male characteristics. It could be a result of too much product from other genes. You don’t need to know those genes. At this point in time, we’re getting kind of a lot of detail but those other genes that can actually override the SRY. Clearly, as we learn more, we know more things are involved in sex determination, SRY is a major one. But if there’s too much of these other genes then perhaps we can accidentally stimulate male development.

03:56 One area that we do have a little more understanding about is CAH or congenital adrenal hyperplasia in which we have a disruption in the production of sex hormones that results in a disruption in the production of sex hormone such that we may get more androgen production.

04:19 If that happens during critical periods in development, it’s completely possible to have an XX individual display, at least partially as a male because of overproduction of particular hormones at certain points during development.