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!

Can turner syndrome cause a piece missing on one x, so it resembles y? Or is it clear that it's a broken x?

But a female can’t be missing the SRY gene because they’re not meant to have one in the first place!

The only sex that can be missing it is… male…

????

If SRY is the main determiner of sex then why is XY-missing SRY considered a DSD? Surely that would just be (and I’m sure this plays into TRAs) a different way of being female?

If so, it can’t be a DSD, can it? In that it’s just an unusual variation, assuming that sex is determined by the presence or absence of the SRY gene??

???

Exactly. They are female because there is no SRY gene.

The disorder relates to the 'missing' gene, insofar as its not where you normally would find it.

The gene being present, or not, is what defines a male or female, regardless of its position.

Do you mean can they have an X chromosome with the SRY attached?

My understanding is that it’s the SRY gene that differentiates between males and females. Usually the SRY gene is found on the Y chromosome.

If it’s missing from the Y chromosome the person is female - Swyer’s.

If there’s a SRY gene on one X chromosome of an XX person they are male - Testicular disorder of sexual development.

Other DSDs have the SRY gene in the right place (on the Y in XY, or not present on either X in XX), but other issues. I think.

That takes us back to ‘women are men without an SRY’.

And- Some men look enough like women to count as women.

Turner is X0, isn’t it?

Yes, I think so. Trying to be hypothetical, but getting myself confused…

Instead of XO, X and broken unclear chromosome.

Don’t know either I’m making any sense at all now.

Or 'men are women with an SRY'.

It's not about looks. it's about having the required genes.

What do you mean? Women clearly need two XX to be fully functional females. XY can never be XX. But in the realms of DSDs, it is really a bit more complicated than that?

Trying to make thoughts more coherent…

Both Swyer’s and De La Chappelle are considered DSDs.
Both are related to the SRY gene - absent in one, present in another.

However…

If the SRY gene is the sole determiner of being male or female - present is male, absent is female, irrespective of chromosomes etc…

OK, no SRY on XY is unusual, but why is it considered a DSD?? If we assume XY should have SRY then I can see why it’s a DSD, but if SRY cannot be considered ‘missing’ (so not a DSD of males), why is it considered a DSD of females? Surely the DSD would be ‘random incomplete Y chromosome in place of expected X’?

Yet it is referred to as a DSD where the SRY gene is absent - but females shouldn’t have the SRY gene at all, so it can’t be absent from them, can it??

I understand.

I think the chromosome can either be completely missing or partially missing.

I wasn't sure whether Turners with an SRY (so 45X-SRY+) had been seen before but I did come across a paper of a rare case of a boy with 1 decended testicle and hypospadias.

You then get into the realms of mosaicism, which is beyond my understanding.

This sort of discussion feels dehumanising.

VSDs are not logic puzzles or thought experiments.

They may vary substantially in their severity and impact but for some people they are a traumatic, medical history.

The question is whether the second X for a female is necessary in making a woman a female. The second X is inactivated by the cells in the body apart from the egg cells.

If a woman is defined by whether she can produce eggs then the second X is important. However, many women can't produce eggs and are still classified as women. So, perhaps a single X with no SRY suffices.

We aren’t talking about individuals. We are trying to understand a technical area of science which happens to be relevant at the moment.

It's all very complicated but as another poster has mentioned, it must be a very traumatic experience for those experiencing a DSD. There may be mumsnetters on here with one who feel awful having their whole identity taken away from them by strangers on the internet.

Is trying to understand the technical aspects of any other genetic disorder or illness equally taboo?
I’ve been on threads trying to understand diagnoses like fibromyalgia. It’s not an attack on me or my experiences when people discuss different presentations or even whether their relative ‘really’ has it.

And in this specific instance, not challenging anyone’s identity but trying to understand the language used around DSDs.

That really does matter.

But mere presence of SRY on XX does not fully equal male - at least not a fertile-and-as-expected male.

The XX part means that the requisite bits to be a fertile male will never be present.

And XX should not have the SRY gene normally, so this has to be a DSD of females, not males?

If we assume that SRY anywhere is male and SRY nowhere is female, then DSDs with missing/misplaced SRY genes can’t be considered anything other than a variation of the normal, surely?

Because if the SRY gene can’t be ‘missing’ and it can’t be ‘misplaced’ …????

Firstly it's not the sole determinator, probably best to go with main determinator (but I don't want to muddy the waters even further!).

Missing refers to where a gene should be. If a gene is not where we would normally expect it, there has been some disorder to the way sex normally develops.

Missing does not refer to a person not having a gene they 'should' have because they are male, because what makes someone male is the gene.

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

Those with Swyers, have a uterus, fallopian tubes and vagina and could possibly get pregnant with medical assistance. Those with Swyers have no male attributes. They don't have a penis, they don't have testes, they don't produce testosterone, they don't have the SRY gene. So why would we say they are male?

A discussion that might be understandable on a genetics, embryology or similar specialist area or forum. It's probably fascinating if this leads you and others to study this in some way.

Here? It's dehumanising and feels similar to participating in what Mary Harrington described as the meat lego matrix at a different scale.

I’m sorry I don’t understand this reference-
Mary Harrington described as the meat lego matrix at a different scale.

Topics that have been discussed on FWR at previous times and may explain how comparatively insouciant you are about discussing this despite the number of times when VSD organisations and representatives have asked not to be used as a wedge issue or dehumanised.

Where’s the dignity for people with DSDs in all of this, as our complex and often emotionally difficult medical conditions are trotted out and prodded by the ignorant, discussed with morbid fascination by people who have no idea about the reality of them? Who gives a shit about what is being done to us?

https://mrkhvoice.com/index.php/2019/12/18/what-is-dignity/

Mary Harrington Meat Lego

in your preferred search engine will return some useful references.

But mere presence of SRY on XX does not fully equal male - at least not a fertile-and-as-expected male.

These are DSDs, they aren't going to produce a 'fertile-and-as-expected male'.

Fertility has nothing to do with what sex you are, your genes do. There are many reasons a male may be infertile, being 46XX-SRY+ is just one of them.

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

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

However, appearing female isn’t the definition of female. It can’t be. Fatima Whitbread had her sex questioned because she didn’t look convincingly female. In some lights, and with good make up, Dylan Mulvaney can appear typically female, although he obviously isn’t.

So female cannot be about appearance or looks.

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

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

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.

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.