Global burden and between-country inequalities in Turner syndrome from 1990 to 2021

Turner syndrome poses a rising global health burden, largely driven by population growth, with marked disparities between high- and low-SDI regions, underscoring the urgent need for equitable prevention, diagnosis, and care strategies worldwide.

Xicui Long, Yong Hu, Mingjie Wu, Lijuan Yang, Wenjiao Jin, Xuesong Han

First published: 07 November 2025

 https://doi.org/10.1111/aogs.70082

https://obgyn.onlinelibrary.wiley.com/toc/16000412/0/0

Transcript

SPEAKER_00 0:00

Imagine a lottery. But um not the kind where you win a giant check. I'm talking about a genetic lottery, a roll of the biological dice that happens right at the moment of conception.

SPEAKER_01 0:10

Completely random.

SPEAKER_00 0:11

Completely random, totally invisible, and for one in every few thousand women across the globe, that role comes up. Missing a piece.

SPEAKER_01 0:19

Specifically a missing piece of an X chromosome. It's a tiny, tiny change in the code, but it just changes the entire trajectory of a life.

SPEAKER_00 0:26

Exactly. And you know, usually when we talk about genetic conditions, you expect a conversation about, well, biology, cells, DNA, that kind of thing.

SPEAKER_01 0:34

Which we will get to. But today is a little different because the research we're looking at, this massive 2025 study from Acta Obstetricia at Gynacologica Scandinavica, it paints a much bigger picture. It suggests that while the genetics might be random, the experience of living with this condition is almost entirely dictated by where you are on the map.

SPEAKER_00 0:54

That is the part that hooked me. We're looking at the geography of genetics. The study is called Global Burden and between country inequalities and Turner syndrome from 1990 to 2021.

SPEAKER_01 1:04

Right. It's by Long and Who and their team.

SPEAKER_00 1:07

And they just crunched 30 years of data to figure out not just how many people have this, but who gets found, who gets treated, and uh who stays invisible.

SPEAKER_01 1:16

And this is the first comprehensive analysis using the global burden of disease database for Turner syndrome. Their goal was really ambitious. Move beyond the clinical definition and actually understand its global footprint.

SPEAKER_00 1:29

So before we start sticking pins in the map, we should probably understand the territory. For anyone who might have just heard of Turner syndrome in passing, maybe in a high school bioclass, let's do a quick refresher. What's actually happening?

SPEAKER_01 1:41

Okay, so let's go back to biology for a second. Typically, females have two X chromosomes. You can think of them as backup systems for each other. They carry all these crucial instructions.

SPEAKER_00 1:52

Right. So you have two copies of the manual. If a page is ripped in one, you can just read it from the other.

SPEAKER_01 1:57

That is a perfect analogy. In Turner syndrome, or TS, one of those copies is either completely gone or it's partially deleted. The backup is gone. And because the X chromosome has instructions for so many different things, not just reproductive stuff, the impact is systemic. It's all over the body.

SPEAKER_00 2:15

The source material lists a whole laundry list of impacts. Short stature seems to be the one everyone knows.

SPEAKER_01 2:20

That's the hallmark, yeah. Almost universally, untreated women with TS will be significantly shorter than their genetic potential would suggest. But that's just what you see on the surface. Right. Underneath, you have things like ovarian dysgenesis, which usually means infertility, no spontaneous puberty, you have congenital heart defects, and those are the most dangerous part, potential kidney issues.

SPEAKER_00 2:43

So it's not just being short, it's a whole multisystem medical challenge.

SPEAKER_01 2:47

Aaron Powell Exactly. And it affects roughly, say, 25 to 50 out of every 100,000 females. It's not incredibly common, but it's not super rare either. It's right in that zone where it needs a lot of medical attention.

SPEAKER_00 2:58

Aaron Powell Okay, so that's the biology. Now let's get into the global snapshot from this study. They looked at data from 1990 all the way to 2021. When they zoomed out, what are the headline numbers? How many people are we talking about?

SPEAKER_01 3:09

As of 2021, the estimated global prevalent cases, so the number of people living with the condition, was just over half a million. About 531,784.

SPEAKER_00 3:21

Wow. Over half a million women and girls.

SPEAKER_01 3:24

Correct. And in that same year, 2021, there are about 24,000 new cases diagnosed, the incidence. But here's the trend that really jumps out from the data.

SPEAKER_00 3:33

Okay.

SPEAKER_01 3:34

Between 1990 and 2021, the total number of people living with TS went up by 27.7%.

SPEAKER_00 3:40

That sounds like a big spike, almost a 30% jump. Is the condition is it becoming more common? Is something causing more chromosomal errors?

SPEAKER_01 3:47

Aaron Powell That's the first question everyone asks. But the study did something called a decomposition analysis to figure out the why. They wanted to see what the driver was.

SPEAKER_00 3:54

And it wasn't genetics.

SPEAKER_01 3:54

It wasn't genetics. The mutation isn't happening more often. Trevor Burrus, Jr.

SPEAKER_00 3:57

So the dice aren't rolling differently.

SPEAKER_01 3:58

No. The age standardized rates, so the rate per person stayed almost completely flat. The huge increase is driven by one thing: pure population growth.

SPEAKER_00 4:07

Ah, okay. Simple math. More people on the planet just means more rolls of the dice.

SPEAKER_01 4:11

Exactly. The escalator of humanity is just going up. In fact, the analysis showed that population growth alone added over 116,000 cases. If the population had stayed the same, we wouldn't see this jump.

SPEAKER_00 4:23

Aaron Powell That makes sense. But was anything pushing the numbers down at all?

SPEAKER_01 4:26

Aaron Powell Yeah, there were some counterforces. Population aging and uh what they call epidemiological changes.

SPEAKER_00 4:33

Yeah.

SPEAKER_01 4:33

You know, basically better health care. They actually did work to reduce the prevalence a little bit.

SPEAKER_00 4:38

But not enough.

SPEAKER_01 4:39

Not enough. The sheer force of population growth just overpowered everything else. It's like trying to swim against a really strong current.

SPEAKER_00 4:45

Aaron Powell So the wave of humanity gets bigger and it drags the case numbers up with it. Okay. Now here is where it gets really interesting for me. The study broke it down by country. This is the whole geography of diagnosis. If I asked you where most of these women live, what does the data say?

SPEAKER_01 5:01

Aaron Powell Well, if we're talking absolute numbers, just the raw count of patients, it pretty much mirrors the world's population centers. The highest numbers are in India with about 92,600 cases, then China with roughly 57,000. And the United States is third with around 42,000.

SPEAKER_00 5:16

So big countries, big numbers, that tracks. If you have a billion people, you're gonna have more of everything.

SPEAKER_01 5:21

Precisely.

SPEAKER_00 5:22

Yeah.

SPEAKER_01 5:22

But here is the twist. If you look at the prevalence rate, the number of cases per 100,000 people, the map changes completely.

SPEAKER_00 5:31

Who comes out on top then?

SPEAKER_01 5:33

New Zealand, the USA, and Belgium. New Zealand is at the top of the list with about 32 cases per 100,000.

SPEAKER_00 5:39

Wait, hold on. Why? Is there some genetic reason for that in New Zealand? Why would their rate be so much higher than India's?

SPEAKER_01 5:46

It's highly, highly unlikely to be genetic. This is almost certainly a reflection of the healthcare system.

SPEAKER_00 5:51

Oh.

SPEAKER_01 5:51

High prevalence rates in wealthy countries like New Zealand or the U.S., they reflect two things. Better survival rates, and this is the key, better diagnostic capacity.

SPEAKER_00 6:02

I see. So the women in New Zealand are being counted because they're being found.

SPEAKER_01 6:05

Exactly. To be prevalent in a database, two things have to happen. One, you have to be identified by the medical system, and two, you have to survive. And in a a lot of the developing world, baby born with a severe heart defects, common in TS, might just pass away in infancy.

SPEAKER_00 6:20

And without a genetic test, the cause of death is recorded as, I don't know, heart failure.

SPEAKER_01 6:24

Exactly. Or a girl might grow up just thinking she's naturally short and infertile, and she never gets the test to confirm why, so she never enters the data.

SPEAKER_00 6:32

Aaron Powell So, in a way, the map of high prevalence isn't a map of where the disease is, it's a map of where the doctors are.

SPEAKER_01 6:39

Aaron Powell That's a profound way to look at it. And I think it's right. And we see the inverse too. The lowest numbers were in places like Noah and Tokelau. Now part of that is just tiny populations, but it also reflects limited diagnostics.

SPEAKER_00 6:51

Aaron Powell The study also mentions some big regional shifts. It said Western sub-Saharan Africa saw a huge jump.

SPEAKER_01 6:57

Aaron Powell A massive jump. 142% increase in prevalence. Again, that's driven mostly by the population boom in that region. But you contrast that with Eastern Europe, which actually saw a decrease of about 21%. Trevor Burrus, Jr.

SPEAKER_00 7:09

A decrease. Is that just because the population is shrinking there?

SPEAKER_01 7:12

Aaron Powell Partly a population decline, yeah. But it also hints at something else we need to talk about, which is prenatal screening. And that brings us to the inequality gap.

SPEAKER_00 7:21

Aaron Powell Right. This is the part of the study I really had to read a couple of times. They use this term SDI sociodemographic index. Basically a way of ranking how developed a country is. And I'm seeing something that looks like a contradiction.

SPEAKER_01 7:35

You've spotted the paradox.

SPEAKER_00 7:36

It feels backwards. The data says that wealthy regions, places like Western Europe, North America, they have the highest prevalence, the most women living with Turner syndrome. Correct. But then it says the incidence, the number of new babies being born with it, is actually higher in low-income developing regions. How can you have more babies born with it but fewer people living with it? Trevor Burrus, Jr.

SPEAKER_01 7:58

It's a heavy realization when you put it together, isn't it? It points to two completely different realities. And let's start with the wealthy world. Why is incidence dropping there?

SPEAKER_00 8:06

I'm guessing. Medical intervention.

SPEAKER_01 8:08

Prenatal screening. In high SDI countries, non-invasive prenatal testing is becoming standard. A simple blood test from the mother. If a fetus is flagged for Turner syndrome, families have a choice. And many opt for elective termination. So the birth rate of the condition drops.

SPEAKER_00 8:24

Okay, that explains lower incidence in, say, the UK or US, but they still have high prevalence.

SPEAKER_01 8:30

Because if you are born with TS in a wealthy country, the healthcare system catches you. You get the heart surgery, you get growth hormones, estrogen therapy, you survive, and you live a long life. So the pool of people with it stays large.

SPEAKER_00 8:45

And in the low SDI regions, the data says incidence is rising.

SPEAKER_01 8:49

Rising because the population is booming. More people, more genetic dice rolls, but there's very little prenatal screening. So the babies are born.

SPEAKER_00 8:57

But they aren't showing up in the living with it numbers.

SPEAKER_01 9:00

Which brings us to this concept. Sociologists call it missing women.

SPEAKER_00 9:03

They aren't in the data because they aren't surviving.

SPEAKER_01 9:06

Or they're just never identified. If a baby is born in rural Niger with a common heart defect from TS and there's no pediatric cardiac surgeon for 500 miles, that child likely dies in infancy. The diagnosis dies with them.

SPEAKER_00 9:19

Wow. That really it just highlights that biology is only half the story. The other half is about resources.

SPEAKER_01 9:25

It connects right to this efficiency gap analysis they did. They used a method called frontier analysis.

SPEAKER_00 9:30

Now, this part I loved. It sounds like something out of science fiction, but it's really just a way of grading countries on their homework.

SPEAKER_01 9:37

That's a good way to think about it. It's an efficiency score. They asked, given how much money and resources a country has, how well are they managing the burden of this disease?

SPEAKER_00 9:46

And I assume the wealthy countries got an A plus N. I mean, if you have the budget, you have the efficiency.

SPEAKER_01 9:51

You would think so. But the data says no. And this was a real shocker in the paper. Countries like New Zealand, Belgium, and the USA showed large efficiency gaps.

SPEAKER_00 10:02

Aaron Powell Wait, how we just said they're great at diagnostics at keeping people alive. How can they be inefficient?

SPEAKER_01 10:08

Aaron Powell Because burden in this study isn't just about death. It includes years lived with disability or YLDs. Okay. In wealthy countries, women are surviving, which is great.

SPEAKER_00 10:18

Uh-huh.

SPEAKER_01 10:19

But they are living with significant health challenges that aren't being managed well.

SPEAKER_00 10:23

Aaron Powell So survival isn't the only metric for success.

SPEAKER_01 10:26

Aaron Powell Exactly. Women are surviving into their 40s, 50s, 60s, but they're dealing with untreated infertility, autoimmune issues, hearing loss, psychosocial struggles. The efficiency gap means that even though the system saved their lives, it's failing to manage their quality of life.

SPEAKER_00 10:42

Aaron Powell It's like buying a Ferrari and then never changing the oil. You've got the high-performance machine, but you aren't maintaining it.

SPEAKER_01 10:49

Aaron Powell That's a perfect analogy. The study is just these wealthy systems are good at acute care, fix the heart, fix the height, but terrible at the long game.

SPEAKER_00 10:58

Aaron Powell And what about the low SDI countries? What about their efficiency gaps?

SPEAKER_01 11:02

Aaron Powell The study showed countries like Niger and Somalia had very small gaps. They looked efficient.

SPEAKER_00 11:07

Aaron Powell But that can't be right. We just said they have almost no healthcare access for this.

SPEAKER_01 11:11

Aaron Powell It's a data illusion. And uh the researchers are very clear about this. When you have massive under-reporting, massive underdiagnosis, the burden in the data looks artificially low. Trevor Burrus, Jr.

SPEAKER_00 11:22

Right. You can't have a disability burden on paper if the patients aren't even in the system.

SPEAKER_01 11:26

Aaron Powell Exactly. So they look efficient simply because all the suffering is invisible to the database.

SPEAKER_00 11:31

Aaron Powell That is a stark reminder that data always needs context. You can't just look at a chart and say Somalia is handling this better than Belgium.

SPEAKER_01 11:39

No, absolutely not. It tells us that what we define as success has to be different depending on where you are.

SPEAKER_00 11:46

Let's pivot to the timeline of a patient's life, because the when of diagnosis seems just as important as the where. The study mentions the median age of diagnosis is 15. 15?

SPEAKER_01 11:58

Think about that. That means half of all girls with TS aren't finding out until they're teenagers.

SPEAKER_00 12:03

That feels incredibly late. I mean, surely you'd notice the growth issues before then.

SPEAKER_01 12:07

You'd think so. But often if a girl is just short, it gets dismissed. Oh, she's a late bloomer, or her parents are short. The diagnosis often only happens when puberty just doesn't start.

SPEAKER_00 12:19

And why is age 15 a problem? What's the difference between catching it then versus at age five?

SPEAKER_01 12:24

Well, by 15, the growth plates in the bones are already fusing. It's often too late for growth hormone therapy to make a big difference for final height. And more importantly, you've missed 15 years of screening for heart defects or kidney issues.

SPEAKER_00 12:37

Aaron Powell So the later the diagnosis, the worse the outcome.

SPEAKER_01 12:40

Statistically, yes. Diagnosis after age twelve is linked to poorer long-term outcomes.

SPEAKER_00 12:45

Aaron Powell The study mentioned three peaks of diagnosis. When are we finding these cases?

SPEAKER_01 12:50

Aaron Powell So the first peak is prenatal or at birth. Those are usually the more severe cases with visible signs like a web neck. The second peak is that five to twenty age range, triggered by height or puberty issues. And the third peak is surprisingly late. Usually in fertility. A woman tries to conceive, can't, goes to a specialist, and only then discovers she has Turner syndrome. Imagine going three decades without knowing this fundamental fact about your own genetics.

SPEAKER_00 13:20

That must be a massive psychological shift. Here is the reason for everything.

SPEAKER_01 13:24

It is, and it speaks to the changing nature of the burden. The study found that globally the burden of the disease peaks in kids under five. That's mostly in the developing world, where those early years are a fight for survival. But in the wealthy world In high SDI regions, the burden peaks in young adulthood, ages 20 to 34. Survival is high, so the challenge shifts. It becomes about managing the long-term stuff. Fertility, cardiovascular monitoring, the higher risk of diabetes.

SPEAKER_00 13:51

This connects directly to that loss to follow-up issue the authors bring up. This part really frustrated me. We spent all this effort diagnosing them as kids, and then what? We just say, good luck.

SPEAKER_01 14:01

Essentially, yes. Picture a girl with TS. She's 16. She sees a pediatric endocrinologist every six months. She's measured, she's monitored, she's in the safety net.

SPEAKER_00 14:10

Okay.

SPEAKER_01 14:10

Then she turns 18. She graduates high school, she graduates from her pediatrician. Now she has to find an adult specialist. But maybe she feels fine. She's done with growth hormone shots. She just wants to be a normal young woman.

SPEAKER_00 14:22

So she stops going to the doctor.

SPEAKER_01 14:24

She falls right off the cliff. And the problem is the silent killers, the high blood pressure, the aortic dilation, they don't stop because she turned 18. The study highlights this transition from pediatric to adult care as the single biggest point of failure in high-income countries.

SPEAKER_00 14:39

That just seems like such a fixable problem.

SPEAKER_01 14:42

It is. The authors explicitly call for transition clinics, you know, bridges between the two worlds. Because right now, we are saving these girls as children, only to lose them to preventable issues as adults.

SPEAKER_00 14:56

It really hammers home that healthcare means something totally different depending on the context. In one place, it's just getting a basic genetic test, and in another, it's a transition clinic for young adults.

SPEAKER_01 15:06

And in both places, it's about seeing the patient as a whole person, not just a list of symptoms.

SPEAKER_00 15:12

So let's look forward. The study projects out to 2050. What does the future look like?

SPEAKER_01 15:16

Well, the numbers are going to keep climbing. They used a forecasting model, and they predict absolute prevalence will reach about 541,000 cases by 2050.

SPEAKER_00 15:26

But incidence new cases, that's expected to drop a little bit.

SPEAKER_01 15:29

A modest decline, yeah. From about 24,000 down to maybe 14,600. And that's assuming the current trends in prenatal screening and family planning continue.

SPEAKER_00 15:39

So we'll have fewer babies born with it, but a larger population of adults living with it.

SPEAKER_01 15:43

Exactly. The population of people with TS will get older, the age standardized rates will decline a bit, but the absolute burden on healthcare systems is not going away.

SPEAKER_00 15:52

So what's the takeaway for policymakers? If you were sitting across from the World Health Organization with this study, what are you telling them?

SPEAKER_01 15:59

I'm telling them that a one-size-fits-all strategy is useless. For the low SDI countries, especially in Sub-Saharan Africa and South Asia, the priority has to be basic diagnostic infrastructure. You can't treat what you don't find.

SPEAKER_00 16:13

And for the high SDI countries.

SPEAKER_01 16:15

The focus has to shift to quality of life. We need to close that efficiency gap. It's not enough to have the fancy technology. We need organized lifelong care strategies. We have to stop losing women in that transition to adulthood.

SPEAKER_00 16:29

It's a call for a much more nuanced approach. You know, what sticks with me most from this whole thing is that invisibility aspect. We have data for the 531,000 women we know about, but that efficiency gap, the low prevalence in developing nations, it's a bit haunting.

SPEAKER_01 16:42

It creates a ghost population in the data.

SPEAKER_00 16:45

Exactly. And that's the thought I want to leave our listener with. We know incidence is higher in low-income countries, but prevalence is reported as lower. That gap represents real human lives. How many thousands of women are out there right now in rural India or Nigeria struggling with infertility, struggling with fatigue, living with Turner syndrome, without ever knowing the name for the thing that defines so much of their reality?

SPEAKER_01 17:11

It's a profound question. And until we close that diagnostic gap, their stories just remain untold.

SPEAKER_00 17:17

A huge thank you to the researchers Long and Hugh for this incredible work, and thanks to you for walking us through it.

SPEAKER_01 17:22

My pleasure.

SPEAKER_00 17:23

And to our listener, thanks for taking the deep dive with us. We'll see you on the next one. Stay curious.