Ep. 83 | The Disappearing Girl

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In 2011, Emma was a vibrant 13-year-old with Down syndrome, water skiing with her sisters on sunny afternoons, laughing with her friends, and excited to start middle school.

But just months later, something changed.

Emma became withdrawn, unresponsive.

Her bright smile faded, replaced with a vacant stare.

She stopped talking, stopped engaging.

She wasn't the girl she used to be.

The world that once felt full of possibilities now seemed impossibly distant.

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From Balin Studios and Wondery, I'm Mr.

Balin, and this is Mr.

Ballin's Medical Mysteries, where every week we will explore a new, baffling mystery originating from the one place we all can't escape, our own bodies.

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This episode is called The Disappearing Girl.

On a hot day in July of 2011, Dr.

Barbara Elliott stood on a lakeside dock in Minnesota behind three of her four teenage daughters.

The girls were all looking out over the water where their fourth sister, 13-year-old Emma, was learning how to water ski.

Their father William was driving the motorboat, and behind it was Emma getting pulled right along.

At some point, Emma stood up on her skis, but only long enough to hit a big wave and go tumbling down beneath the surface again.

But all the sisters cheered when their dad circled back around and Emma motioned from the water that she wanted to try again.

And this time, once the boat started going, Emma was able to stay upright a lot longer and her older sisters went crazy, jumping and clapping as Emma sailed across the water.

Emma's mother, Barbara, beamed with pride.

And not just because Emma had learned to water ski in just a single afternoon, but because she was just very proud of Emma's determination.

Emma had Down syndrome, which meant that she was born with an extra copy of chromosome 21.

The extra chromosome affected the way her brain developed, so she was growing up with some mental and physical challenges.

And so Barbara, who was a developmental pediatrician, knew full well how much harder learning how to water ski would be for Emma than it would be for her sisters.

But Barbara realized very early on that she should never doubt Emma.

Emma had always been outgoing and athletic.

She loved soccer and swim practice.

She took ice skating lessons and karate classes.

She was also a social butterfly and was looking forward to starting middle school in the fall.

Basically, whenever Emma set her mind to something, she always thrived.

Emma skied for a few more seconds before losing her grip on the tow rope and splashing back into the water.

But a second later, Emma came back up for air and gave her family a big thumbs up.

Barbara could see Emma's big smile all the way from the dock.

Five months later, in December, Barbara meandered her way through a Christmas tree farm, enjoying the smell of freshly cut pine trees.

Her daughters were up ahead, choosing which Christmas tree they should strap to the roof of the car and bring home.

William was next to them, setting up his camera on a tripod.

This had become a sort of annual tradition in their family.

They would come to this farm to pick out their tree and take a family Christmas photo.

In the past, the way this typically went is Emma would run all around the farm until she found the perfect tree, at which point she would loudly announce it to the rest of her family, and then that would be the tree they would choose.

But this year, Emma seemed checked out from the whole process.

She kept staring off into space while her sisters tried to get her attention.

Her oldest sister, Mallory, kept asking her questions, but Emma just ignored her.

And then when she finally answered, her words were slow and labored, like she was talking with peanut butter in her mouth.

Barbara wondered if this was just typical teenager stuff.

Emma was 13 after all.

Her personality was bound to change a little bit.

But Barbara still couldn't help but feel worried about her youngest daughter.

She wondered if maybe something was going on at school that had her mind occupied.

William finally got the camera all set up and then told the girls to smile for a photo.

But Emma just stared at the ground.

Barbara called Emma and told her to look up, and she did, but by the time the camera flashed, Emma was staring back at the ground again, lost in her own world.

William had to take the picture three more times just to get a shot with Emma looking at the camera.

And even then, she wasn't smiling.

One morning, a few weeks later, Barbara was in the kitchen pouring herself a bowl of cereal.

The rest of her family was already eating around the table.

Well, all of them were eating, except for Emma, who was just slumped over in her chair, picking at her food and staring staring at the half-melted Christmas candles in the center of the table.

She'd been quiet all morning, even though Mallory had been asking her questions, like whether she was excited to return to school and see her friends again.

And so eventually, Mallory just began asking Emma really basic questions that, frankly, she didn't care about the answers at all, like what day of the week is it and what time is it?

But Emma didn't even look up.

At this point, Barbara exchanged a worried glance with her husband William and also her other daughters.

Emma had been withdrawn like this for all all of winter break.

She avoided eye contact and barely spoke to any of them.

She hadn't helped them decorate the Christmas tree, and she got moody whenever anybody asked her questions.

And even stranger, Emma hadn't wanted to see any of her friends over break.

But as Barbara thought back even farther, like over the whole last few months, she realized Emma had been through a very difficult time.

Emma had just started middle school.

and she was immediately taken out of general education and put in special education classes for the first time in her life, which could have felt like a demoralizing setback.

Maybe she was so upset about what was going on at school that that was having a profound impact on her life.

You know, she wasn't sleeping very well, perhaps because she was thinking about this stuff, and perhaps the lack of sleep was making her irritable and not really interested in talking to anyone.

But trouble at school didn't really explain why Emma now was just completely ignoring her sister.

Barbara knew Emma would never give Mallory the cold shoulder for no reason.

This behavior behavior was radically out of character.

Emma adored her big sister.

Barbara had worked in pediatric medicine long enough to know that whatever was going on with Emma was not normal.

And so she would have to see her doctor.

When Barbara and Emma went in to see her pediatrician, he immediately ordered a full medical workup for Emma.

He ran all sorts of tests like an EEG, which measures electrical activity in the brain, also a sleep study, a vision and hearing screen, and full blood work.

But none of these tests showed anything wrong with Emma.

But just to make sure they covered all their bases, the pediatrician also ordered an MRI of Emma's brain, which creates a detailed scan of the body using magnetic waves.

And the MRI did show a few small abnormalities in her brain, but nothing that would explain the apathy, lack of focus, and intellectual decline Emma seemed to be experiencing.

And so after that, the pediatrician said he had no further tests to recommend.

Whatever was going on with Emma, it didn't seem like a problem he could fix.

Several weeks later, after the winter break was over, Barbara was upstairs helping clean Emma's room.

Emma used to clean it herself, but she wasn't doing her chores anymore.

On top of Emma's increasing social isolation, she'd also begun having these frequent crying episodes.

But just as the tears would dry up, she'd burst into fits of laughter.

And also, Emma had become hypersensitive to noise and touch.

She wouldn't even let her mom brush her hair.

She barely slept at all, which Barbara knew was taking a further toll on her mood and energy levels.

Her daughter seemed like a shell of her former self.

It was emotionally very painful for Barbara to clean Emma's room these days, dusting the trophies and mementos that lined her shelves.

They were all reminders of who Emma used to be, a girl who was thriving.

Once Barbara was finished dusting, She picked up Emma's backpack, which was overturned on the floor.

And as she lifted it up, a small bundle of papers fell out.

She was about to set the papers on Emma's desk when she realized the papers were actually letters written by Emma to her favorite teachers.

Now, Barbara would never invade her children's privacy if she could help it, but given everything going on with Emma, she gave herself permission to dive into these notes.

They were all about Emma's struggles in school.

Some of the students in her new special education classes were too aggressive, she wrote.

They would throw fits and shout, and this really upset her.

But the teachers yelled at her too, which upset her even more.

She didn't like school anymore, and she just wanted to go back to fifth grade.

Barbara noticed that all these letters were written back in September and October, about six months ago, right around the time that Emma first became lethargic and reclusive.

Barbara realized that Emma had known all those months ago that something was wrong.

She'd written these letters basically asking her teachers for help, but for whatever reason, it appeared like she was either too shy or too overwhelmed to actually deliver them.

Reading her daughter's notes was heartbreaking for Barbara, but it was also fairly informative.

She began to wonder if maybe she was wrong to think that her daughter's struggles were a medical issue.

If Emma was having this much trouble adjusting to her new school, maybe her condition was actually psychological.

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Several months later, in the summer of 2012, Barbara sat at the dinner table watching Emma eat.

Emma was bent over her plate, shoveling food into her mouth and swallowing it so quickly she barely had time to chew.

Emma had been an eating machine over the past few months, but tonight she was really gorging herself.

Even though Barbara was a pediatrician herself, she could not explain why her daughter's behavior had changed this much.

After Barbara had found Emma's letters, she and her husband had taken Emma to every therapist and psychiatrist they could find.

And one psychiatrist, who specialized in children with disabilities, diagnosed Emma with post-traumatic stress disorder, or PTSD, due to the difficult transition from elementary school to middle school.

She'd prescribed Emma antidepressants, and at first they appeared to work.

But then she complained that the medication made her feel dizzy, and so they stopped it.

And unfortunately, the next medication they tried made her insomnia worse, and the next one after that gave her stomach pain.

The only drug that Emma could tolerate was memantine, a medication used to treat memory loss in dementia patients.

And in reality, it only helped a little bit.

Nothing was able to bring Emma back to her old self.

Barbara was frustrated that after consulting with so many doctors and therapists, no one could find a treatment that worked for Emma, or could even diagnose exactly what was wrong.

She was beginning to realize that if she and her family were going to get Emma back, she was going to have to find answers herself.

Almost a year later, in 2013, Barbara stood in front of a big lecture hall clicking through slides on a projector.

She was a speaker at a conference of Down syndrome researchers and she was presenting her daughter's case to the community.

She fought to keep a neutral face when she played videos of her daughter water skiing and enjoying time with her friends and family the way she'd been just a few years ago.

But as painful as that was, Barbara pressed on, explaining all the details of Emma's startling regression.

And as she presented her daughter's case, she couldn't help but notice a few audience members wiping tears from their eyes.

A couple days later, Barbara received an email from a woman who had seen her presentation.

The woman's name was Lucy Duncan, and like Barbara, Lucy was searching for answers.

When Lucy's daughter, Sierra, was 20 years old, she went through a very similar regression to Emma.

Lucy had tried many treatments for her daughter, but all of them were unsuccessful.

Lucy had found a medical researcher who'd taken some interest in Sierra's case, but so far nothing had come from that either.

Barbara thought Lucy sounded just like her.

They were both mothers desperate to bring their daughters back.

But also, as Barbara read this email, something else clicked.

There were other people out there with Down syndrome who were also suffering from this mysterious, steady decline.

And so Barbara wrote back to Lucy and promised they would stay in touch.

They'd compare notes in the coming months and hopefully figure out what was causing their daughters to regress.

Or, better yet, find a treatment plan that actually helped their kids.

More than a year later, Barbara was sitting inside of a doctor's office, watching as a nurse used what looked like two robot arms to touch Emma's head.

These arms were giant magnets that stimulate nerve cells in the brain to try to relieve symptoms of major depression.

Recently, Barbara had taken Emma to a new psychiatrist who diagnosed her with catatonia, a disorder that interrupts normal brain function.

People with catatonia struggle to communicate and lose their motor skills.

This psychiatrist had recommended a four-week course of this cranial nerve stimulation in hopes it would improve Emma's mood and help her engage with her friends and family again.

Thankfully, this sort of bizarre treatment did not seem to bother Emma.

who was now 16 years old.

She was watching Taylor Swift videos on her phone, seemingly unaware that the nurse was pulling a strap across her head and getting ready to turn on these robot arms.

The nurse flipped on the machine, and a metallic clicking sound filled the room.

Barbara winced, but Emma seemed absolutely fine.

So Barbara stopped worrying and leaned back in her chair.

On the way home, Barbara didn't notice much of a change in Emma.

But one night, after a few weeks of treatment, Barbara went upstairs to get ready for bed.

She passed Emma's room, expecting to see the desk lamp on and Emma sitting at her desk watching YouTube, but instead, the room was dark.

Curious, Barbara poked her head in, and to her shock, Emma was in bed, sound asleep, not staring at the ceiling racked with insomnia, not pacing or zoning out or acting moody,

just peacefully sleeping.

Barbara felt an overwhelming sense of joy.

Now, Emma might not be able to communicate with the outside world just yet, But Barbara hoped this was a sign that maybe she was feeling more peaceful inside.

It was a small glimpse of who Emma used to be, and Barbara hoped that it meant the nerve stimulation treatments were working and that the old Emma was on her way back.

Two years later, in 2016, Barbara sat down in the living room and opened up her laptop.

Emma was 18 years old now, and they were still searching for a comprehensive treatment plan.

Nerve stimulation had helped Emma, but she was by no means back to her normal self.

She was still very withdrawn anytime they were out in public, and she suffered from severe obsessive-compulsive disorder.

Obsessive-compulsive disorder, or OCD, is a condition where people have unwanted thoughts and feel the need to do certain actions to ease their anxiety about them.

They can interfere with their daily life.

But, as always, her mom, Barbara, had a plan.

A few days earlier, Barbara had spoken with Lucy, the woman who contacted her after her presentation at the Down syndrome conference.

Lucy's Lucy's daughter, Sierra, was also still struggling, and so they wanted to see if there were any other parents of Down syndrome children out there who had watched their kids regress and their personalities disappear.

So they had started a Facebook support group.

And now, Barbara clicked on that group's page, and she was immediately overwhelmed.

It had been up for only a few days, but already dozens of parents had joined.

posting stories of their once thriving children.

And each post had a similar ending.

Their kids suddenly regressed and became a shell of who they used to be without any explanation.

Barbara couldn't believe how many stories like hers were pouring in.

She called Lucy and the two of them stayed on the phone scrolling through the messages together.

Parents asking for help, swapping tips and treatments, and sharing information about physicians who managed to help their kids in some way.

Barbara loved the feeling of not being alone as she read through these posts.

But she also realized something.

Everyone seemed to have tips for mild improvement,

but nobody had met any physician who had actually cracked the code and figured out what actually caused this regression in the first place.

And so, all these Facebook posts forced Barbara to confront a potentially heartbreaking reality.

None of these kids and young adults were getting any better.

It seemed like Emma's future was going to be about just adjusting to this new normal, not about regaining what she had lost.

But Barbara could not accept accept that...

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Several years later, in April of 2020, a pediatrician named Dr.

Christopher DeSantis sat in his Los Angeles office.

Dr.

DeSantis was the director of neuroimmunology at one of the largest pediatric medical centers in the country.

And on this day, he was looking over the results of a spinal tap, a test he had run on one of his patients, a teenager with Down syndrome named Jackson.

One year earlier, Jackson had become quiet and insular and basically stopped interacting with the world around him.

And so Dr.

DeSantis was trying his best to figure out what was wrong with Jackson.

But this was proving to be very difficult to do because it was the COVID pandemic and basically the whole world was shut down.

The hospital required so much protective equipment and social distancing measures that it was very hard to schedule in-person appointments at all, let alone order lab work or other procedures to figure out what was going on.

At least here, alone in his office, Dr.

DeSantis could just focus on his patients and retain some feeling of normalcy.

As he looked over the spinal tap test results, he realized there could be hope that he was close to figuring out the cause behind Jackson's change in behavior.

The results suggested that there was inflammation in Jackson's brain, which is usually caused by some type of infection.

But it can also happen when the patient's own immune system mistakenly attacks healthy tissue that it thinks is an infection.

which is known as an autoimmune disorder.

And people with Down syndrome have a much higher rate of common autoimmune disorders, such as thyroid disorders, celiac disease, and skin conditions.

So to Dr.

DeSantis, it actually made perfect sense that maybe Jackson's regression could be caused by an autoimmune disorder.

The doctor wondered if there was a way to reset Jackson's immune system so that the inflammation in his brain might decrease.

And so he decided to try a standard treatment for immune disorders called intravenous immune globulin, which gradually purifies the immune system.

If it worked, Jackson just might be able to reconnect with the world around him, instead of living inside of this isolating fog.

Two weeks later, Dr.

DeSantis was back in his office catching up on work when he heard a commotion in the hallway, a mix of cheering and applause and stamping feet.

Confused, he opened his door to see what was going on.

and immediately felt a pair of arms wrap around his waist.

He looked down to see his patient, Jackson, locking him in a bear hug.

Then Jackson pulled back, smiling and laughing and telling him he felt better.

Dr.

DeSantis couldn't believe it.

This was a completely different kid from the near-catatonic teenager that checked into the hospital a month ago.

The immune globulin treatment, in combination with a few other treatments, had brought Jackson back to life, so to speak.

In fact, it was so successful that right away, Dr.

DeSantis wondered if maybe other patients with Down syndrome could benefit from this treatment.

And sure enough, a few months later, when Dr.

DeSantis was surfing Facebook, he stumbled upon a support group for families with Down syndrome children who had regressed.

Dr.

DeSantis immediately reached out to the group and asked if he could post about his own research.

Lucy Duncan was excited and told Dr.

DeSantis to please post it.

By this point, the Facebook group that she had set up with Barbara had hundreds of members who were eager for more and new information.

And so the moment Dr.

DeSantis began posting about his experimental treatment that had presumably cured his patient Jackson, responses on this page poured in.

Not long after that, Lucy flew with her daughter Sierra out to Los Angeles to meet with Dr.

DeSantis.

He administered the same course of treatment for Sierra as he had for Jackson, and right away, Sierra did show signs of improvement.

But then her progress just stopped.

She didn't have the same dramatic turnaround that Jackson experienced.

Dr.

DeSantis suggested that maybe because Sierra had been in regression much longer than Jackson, that that was why the treatment was not as effective.

Lucy was bitterly disappointed, but then she remembered another researcher who had once taken an interest in Sierra's case.

His name was Dr.

Antonio Rivera.

Now, he didn't have any answers at the time for what was going on with her daughter, but he had told her that he was going to continue his research.

Lucy thought that maybe Dr.

Rivera should know about Dr.

DeSantis' research.

So she pulled out her phone and sent an email to both doctors introducing them.

She hoped that just maybe they might find a way to help patients like her daughter and the hundreds of other people on their Facebook group whose children had been in regression for five or even ten years.

Following Lucy's introduction, Dr.

DeSantis reached out to Dr.

Rivera, and he was delighted to learn that Dr.

Rivera had continued his Down syndrome research.

Dr.

Rivera suspected that this regression was caused by the extra chromosome 21 that people with Down syndrome are born with.

He believed the extra chromosome caused them to generate an overly powerful immune system that can sometimes turn on the body itself, making people sick instead of protecting them from disease.

This would explain the inflammation Dr.

DeSantis had discovered in the brain of his other patient, Jackson.

Dr.

Rivera suspected that medical researchers had not noticed this autoimmune disorder until now, at least in part because of the history of bias in the medical field about people with Down syndrome.

And Dr.

DeSantis agreed.

If a typical teenager suddenly became a lethargic and moody loner, their doctors would treat it like a major issue.

But Drs.

DeSantis and Rivera both suspected that doctors generally paid less attention to antisocial behavior in people with Down syndrome because they already had an intellectual disability.

Dr.

DeSantis was thrilled to meet a doctor whose research aligned so closely with his own.

The two of them decided to work together to bring attention and resources to this autoimmune disease.

In 2022, Dr.

DeSantis took the lead on a paper that named the condition Down syndrome regression disorder.

In the paper, he explained that it affects between 1 and 5% of those with Down syndrome.

In June of 2023, Emma finally received an official diagnosis after 12 years of progressing.

In October of that year, she began immune globulin treatment.

At that point, Emma was 25 years old, and her recovery was not as dramatic as some of Dr.

DeSantis' younger patients.

But the treatment still did make a significant improvement in her quality of life.

She was now able to at least smile and joke around again.

Recently, Emma graduated from a local university transition program for people with disabilities.

She's making friends again, performing in community theater, and water skiing, something she hadn't been able to do for 10 years.

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From Ballin Studios and Wondry, this is Mr.

Ballin's Medical Mysteries, hosted by me, Mr.

Ballin.

A quick note about our stories.

They're all inspired by true events, but we sometimes use pseudonyms to protect the people involved.

And some details are fictionalized for dramatic purposes.

And a reminder, the content in this episode is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

This episode was written by Aaron Lamb.

Our editor is Heather Dundas.

Sound design is by Ryan Potesta.

Our senior managing producer is Callum Plus.

And our coordinating producer is Sarah Mathis.

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Our associate producers and researchers are Sarah Vitak and Teja Palaconda.

Fact-checking was done by Sheila Patterson.

For Bollin Studios, our head of production is Zach Levitt.

Script editing by Scott Allen and Evan Allen.

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Production support by Avery Siegel.

Executive producers are myself, Mr.

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