A technical question about Swyer Syndrome and CAIS

[QuimReaper]

I have become interested in these syndromes as a result of their getting a lot of discussion on these boards, and although this question has nothing do with FWR, posters here seem exceptionally well-versed in DSDs, so I hope nobody minds me popping a couple of incidental questions here.

First: my understanding is that without hormone treatment, children with Swyer Syndrome never experience puberty due to lack of gonads. I'm just wondering, what actually happens in cases where Swyer Syndrome goes untreated (as must have happened historically and globally)? Or in general when someone doesn't experience puberty for some other medical reason? Do they stay in a pre-pubertal state for their whole lives, and is their life expectancy normal?

Secondly: my understanding is that people with CAIS produce testosterone, but do not at all respond to it; but that all bodies (XX or XY) produce some amount of oestrogen (I think in the pituitary gland?) and it is this that CAIS cases respond to, resulting in an apparently female appearance.

If I'm right about that, why is it that the same isn't true of Swyer Syndrome? And if I'm wrong about that, how is it that people with CAIS do experience female-typical puberty (breast growth etc., although obviously not menarche) and those with Swyer don't?

Thanks in advance to any clever MNers who can answer these!

I'm sorry, but I think it's fantastic that a feminist forum of mostly women want to further their knowledge on a subject that is core to their movement, what it is to be a woman.

I also think that increasing knowledge in this area leads to society having more understanding and compassion to those with DSD's.

I think it's more dehumanising to repeat Y=male than it is to do some learning and find out that women with a Y chromosome exist.

I realise this.

My point is that SRY alone seems a very odd way to determine maleness. Particularly when it’s attached to a female karyotype.

Why does it seem odd to you?

Because if it isn’t considered to be ‘unusually present’ for a female, then it must be ‘in the right place’ for a male.

In which case the XX-SRY person has just about everything else wrong with their XX-SRY make up, other than the SRY gene itself, which seems to be ok no matter where it ends up!

There are posters here who are very knowledgeable and who probably work in the field.

A forum for genetics specialists would not be the place to ask a lay person question.

I can’t think of a better place to ask, than here.

When we talk of male and female we generally mean what someone appears to be.

I disagree with this. Male and female relate to the sex of something, not what it appears to be.

So those with Swyer’s are considered female because they have all the appearance of being female.

No, they are considered female because they don't have male determining genes.

So female cannot be about appearance or looks.

True, it's about genes.

Usually I’d go with which gametes are produced, but in infertile individuals this is problematic and unhelpful.

Gametes determine the number of sexes something can be, not the sex of individuals.

So next I’d consider chromosomes - XX is normal female, XY is normal male. Occasionally someone may have a variation of either of these.

I would say main rather than normal, but yes.

Wrt the SRY gene - from what others have said about how this determines sex, it appears that this overrides everything else, and there is no right or wrong place for it, just a usually expected place and a more unusual one.

SRY is the main determination sex gene. It is the switch that turns on main development. It is usually found on the Y chromosome. When things don't turn out as expected and the SRY has transposed or not developed this results in a DSD.

*If that really is the case then surely it cannot form part of the symptoms of a DSD at all?

That is, no matter whether it is absent or present it is the right state for that individual. The fact that someone may have XX with SRY isn’t a problem with the SRY, but a problem with the XX instead. Or a problem with the Y part of XY when the SRY is absent.

This makes no sense to me. I’m trying to understand, but if the normal state for XY is +SRY, I cannot see how XY-SRY is not considered an abnormal state for XY individuals, rather than an abnormal state for XX individuals.*

I don't think you can understand because you are still holding on to the belief that male = XY when male = SRY. Having a Y chromosome is not a determining factor in what sex you are.

Obviously XY-SRY- is a disordered state for XY individuals. Nevertheless those individuals are female.

@GCITC

”It is a DSD where the SRY is absent, and therefore those with that DSD have to be female, because there is no SRY.”

This is where I’m really struggling.

The SRY gene can only be absent from males, given that ‘female’ is the state of not having it.

In which case, if the DSD is the absence of the SRY, surely it can only be absent from males?

This is very educating - can I ask then what the cheek swap test determines? If it the XX vs XY? Does that mean further tests might be needed?

Yes, its absence can’t be a disorder.

Yes, for a female competition, they first test for the presence or absence of a Y chromosome. If a Y chromosome is picked up then further testing goes on to determine if there is any DSD involved.

There is no absence of the SRY gene from a male. For this to be true, someone first has to be classed as male and then be told the SRY is absent.

The SRY is what determines a person as male. The gene comes before the person's sex is classified.

(I really am trying hard to explain it so it's easy to understand. My own brain is getting a bit scrambled!)

Its absence from where it is ordinarily found is the disorder.

@UnderratedGenius - you seem to be thinking that someone might have typically male genetics but then the SRY gene is somehow removed which disrupts development. That's not what happens.

Instead think of the SRY gene as what (almost always) determines sex. If an individuals genotype includes SRY, they will be male. Most likely they have XY chromosomes. If they don't, there is a DSD. Vice-versa for female and XX.

@GCITC Thank you for your responses, you’re enormously helpful!

So…
Male and female relate to the sex of something, not what it appears to be.
Indeed. Perhaps my statement was unclear - by appearing I mean ‘meets all the metrics as far as we know.’

Gametes determine the number of sexes something can be, not the sex of individuals.

But each sex produces distinct and different gametes, yes? Which ones are produced by each sex are not interchangeable. Any reason this can’t be used as a shorthand?

I don't think you can understand because you are still holding on to the belief that male = XY when male = SRY. Having a Y chromosome is not a determining factor in what sex you are.

Obviously XY-SRY- is a disordered state for XY individuals. Nevertheless those individuals are female.

Why should XY-SRY be considered a disordered state for XY individuals? I can see this if we say they are male missing SRY, but as you say a sex cannot be missing SRY because SRY is the sex for males, then surely it is at cross purposes to also say that the SRY in an unexpected place or missing from the expected place is a DSD.

Usually XY would have SRY, but if not having it isn’t the disorder of XY males, then surely XY-SRY just becomes a rare presentation for females?

And yet that doesn’t sit well either!

???

In which case XY minus SRY is not a disorder of XY*, but a disorder of XX who have an incomplete Y instead of the second X.

Yes???

*Because the disorder can’t be the missing SRY gene as the concept of ‘missing’ is incorrect because an individual ‘missing’ the SRY is female and females do not have an SRY to ‘miss’. Yes?

😵‍💫

Sure, you can say XY minus SRY is a disorder of XY if you like, but that's not a very meaningful category in this context.

It's equally, and more usefully, a disorder of SRY-negative, i.e. females.

But if they didn’t have the disorder (of the missing SRY) they’d be XY males instead???

Yet it’s not a disorder of males???

Yes, if they had different genetics they'd be a different sex. So would you!

But they have the genetics that they do, and that makes them female.

When we say they are females with a DSD, we are making two separate statements - (1) they are female (SRY-negative) and (2) they have some disorder of sexual development.

Swyer syndrome is a female DSD because only females can have it.

"Female" here describes the actual sex of the affected individuals, not some hypothetical counterfactual individual with different / more typical genetics.

@simmertime

Thanks.

When we say they are females with a DSD, we are making two separate statements - (1) they are female (SRY-negative) and (2) they have some disorder of sexual development.

So what is the disorder bit in this scenario? Females don’t have SRY, so despite the fact these females have XY there is no expectation for them to have SRY.

Is the disorder that they have a Y instead of an X?

I know there will be other things going on too, but do those other issues become the determiner of the disorder bit, making the presence of the Y chromosome incidental and effectively ignored? Or is the Y central because that isn’t a usual presentation in females?

The disorder of sexual development is the lack of ovaries and the consequent effects of that. It's female-specific because only females would be expected to have ovaries.

Is there a condition where XY could have ovaries??

Doesn't seem likely, but …?

Adding:

Because if an XY individual cannot have ovaries under any circumstances, then surely an XY-SRY female cannot have a disorder whereby the ovaries are missing if their body is such that it’s make up doesn’t allow for the possibility in the first place.

This then means we have XX females who are expected to have ovaries and XY-SRY females who are never expected to have ovaries.

In which case, how can the absence of ovaries be considered the disorder in those who have never had the capacity for them?

We effectively end up with two types of female - ones for whom missing ovaries is outside the normal for their body type (XX) and ones for whom missing ovaries is the default (XY-SRY).

Do they have wider hips?
One of the things that makes men faster and stronger is the angle of the thigh bones being straight down to the knees rather than wider at the hips and angled in.

If that makes sense.