Bria’s story

Three years ago, when he was just seven years old, Braxton Dort started making voice recordings with the help of his mother Kara. He wanted to tell people about his little sister, Bria, who has a rare genetic disorder called TANGO2.

A year later, Braxton decided to turn his sister’s story into “A Book About Bria” to raise funds for research into TANGO2.

He took the book to craft fairs and local markets around New Glasgow, where the Dort family lives, and would sometimes sit at those for seven hours, selling and signing a few books, for which he charged $20 apiece.

So far, Braxton has raised about $2,000 for the TANGO2 Research Foundation.

But raising money for research into TANGO2 wasn’t the only reason Braxton wrote the book.

“Bria is special”

It’s a hot summer day when the Dort family invites me into their home to talk about the book, Bria, and how TANGO2 has changed their lives. We all gather in their living room while Bria comes and goes, offering me her toys to hold, and keeping her eye on us.

Braxton starts by telling me more about his little sister and why he wrote the book.

“I thought it would be a nice thing to do for my sister,” says Braxton. “I thought it would be really thoughtful for her, and for people to recognize that life isn’t easy for people like my sister.”

“Bria is special,” he says. “No matter what you do or what she does, she always loves you. Compared to other people who might get mad and might not talk to you, Bria always wants to be friendly and stay with you. And she always smiles, no matter what happens. She always tries her best, whatever she does. I find that really special.”

She doesn’t have a mean bone in her body, Braxton says.

That doesn’t mean that his younger sister doesn’t sometimes get on his nerves, just as any sibling might.

“You have to have a lot of patience when you deal with her,” Braxton says. “Because I have to listen to the same song ten thousand times a day, and I despise that song, ‘How Do You Solve a Problem Like Maria?’”[1]

“Bria got a doll for Valentine’s Day and my Nan [his maternal grandmother Donna Cameron] named it Maria,” Braxton explains. “And we found a song that goes with the name. So Bria likes the song, and I don’t. But I’m forced to listen to it 24/7.”

Sometimes he turns the volume down, Braxton says, but then Bria just turns it back up again.

He tries to help others understand his sister, telling them that even if her verbal skills are not the same as those of her peers, he is convinced her knowledge is. Braxton believes Bria has her own special ways of communicating.

 “She’ll say ‘aaaiii’ and stuff like that most people don’t understand. But she’ll do signs and actions that you can usually make out to determine what she’s saying, or trying to say.”

Braxton was three and Bria just four months old when she had her first health crisis, which involved a long list of symptoms and serious health problems — everything from low blood sugar to enlarged kidneys, uncontrolled seizures, and brain damage.

Braxton still recalls when Bria was on life support in the hospital.

“We thought she was dead, she wasn’t breathing,” he says. “So they went to take her off life support. She started breathing by herself. So it was a miracle.”

In the first four years of her life Bria suffered two comas, 15 total days on life support, consumed massive numbers of medications, and spent long periods in the IWK Hospital in Halifax.

The terrifying first episode

Bria’s father Matt Dort says when Bria was born in 2014, all seemed fine. But when she had her first “episode” at four months, he recalls the terror he felt holding her limp in his arms.

Bria’s mother Kara Dort says that looking back on her daughter’s first months now, she recalls that something did seem slightly amiss; Bria would “stare off,” almost as if she were having an absence seizure that can be common in small children. But that, she notes, is the wisdom of hindsight.

For the first four months of Bria’s life, Kara remembers only “a very happy, healthy baby.”

Then, she says, one night Braxton got sick with something that looked like the flu. She took him to the Aberdeen Hospital in New Glasgow, while Matt stayed home with Bria. When she returned with Braxton, Kara remembers trying to give Bria a bit of milk — she was breastfeeding at the time. Bria wouldn’t feed, and then she began to cry, very loudly.

Kara’s emotions are raw as she recalls the nightmare of Bria’s first episode:

I brought her out to the couch, thinking she might have what Braxton had and maybe we should take her to the hospital, too. Matthew said her breathing was becoming more rapid, and by that point, she was quite pale. So we just kind of wrapped her up. I don’t even know if we had shoes on. We grabbed Braxton and rushed to the Aberdeen Hospital. They weren’t sure what was going on, and they were on a shift change. But when our pediatrician came in, it kind of set off alarms, and he called the LifeFlight. We didn’t really know what was going on.

Kara flew with her baby daughter in the helicopter to Halifax, while Matt drove with Braxton. He says that to this day, he still can’t drive down Robie Street in Halifax because it summons unpleasant memories of that morning when he was stuck there in bumper-to-bumper traffic, watching the clock, and worrying what was happening to their baby girl.

What was happening was much more than just worrisome.

Kara says that when the LifeFlight arrived, Bria was taken straight to the intensive care unit and put on life support, where she remained for three days.

“And when she finally woke up, she never really came back to that four-month-old baby that we had,” says Kara. She recalls the next few months as a “constant kind of battle.”

There were no answers because no one knew what was happening, but Kara says:

There was lots and lots of testing, exhaustive testing with no results. And that’s why we were in and out of the hospital for close to a year. At seven months, she took her second what they call a “metabolic crisis.”

She was on life support for 11 days at that point in time. And on the first day they did say that she wasn’t going to make it … A lot of families have this story where they go through a metabolic crisis, and somehow recover. And there’s just really no explanation as to what puts them into the crisis, or brings them out of it. So obviously, we were just so incredibly grateful, but still had no answers.

After these episodes, Kara and Matt stayed weeks at a time in Halifax while Bria was hospitalized, sleeping in chairs beside her, while Kara’s mother, Donna Cameron, stayed with Braxton in New Glasgow.

“I was a Google machine”

Kara says that for a very long time she was “Captain Google:”

I think I Googled every disease from adrenal gland misfunction, to the hypothalamus to metabolic and mitochondrial diseases, anything I could get my hands on. I would go down a rabbit hole and I’d asked the doctors multiple times. Yeah, I was a Google machine.

However, Kara says that they had a great team of doctors at the IWK working on Bria’s case.

“We were really lucky to have a fantastic doctor, Dr. David Skidmore, who’s a geneticist at the IWK. And he was the lead on Bria’s file from a genetics point of view.”

Then, three years after Bria’s first episode, one day when she was on vacation and downstairs in her house, her phone rang. It was Skidmore. Kara remembers how the call went:

He said, “We’ve got a diagnosis for Bria. Bria has TANGO2.” Dr. Skidmore is very pragmatic, very matter of fact, there’s no sugar-coating anything. And he said, “I’m emailing you the one and only article that we have on it.” And I was like, “Well, what does this mean?” And he said, “Well, from what we know right now, it’s a life-limiting disease. There’s not, you know, a whole lot of research done.”

Kara says she was “devastated.” She called Matt, and then lay in bed for two hours crying.

“Rarest of rare”

Skidmore later told the Dort family that the TANGO2 genetic disorder was so rare, the odds of having it were the same as those of “winning the lotto five times in one year.”

He said that the chances of Matt and Kara meeting, and then of having a child with the variants of the TANGO2 gene that cause health problems were incredibly small, meaning the condition was “the rarest of rare.”

TANGO2, like other genetic disorders, is determined by the combination of genes a child receives from its parents. In this case, both parents need to have one good copy and one bad copy of the TANGO2 gene, and both carrier parents have to pass on the defective copy for a child to have TANGO2-related health problems.

According to the TANGO2 Research Foundation, TANGO2 itself is a “protein-coding gene” on chromosome 22, which belongs to the “transport and Golgi organization family, whose members are predicted to play roles in secretory protein loading in the endoplasmic reticulum.”

That is the kind of complex scientific vocabulary that riddles the literature on TANGO2. Many of the conditions it causes have names that most of us can barely pronounce, let alone understand, and there is also a lot of variation in how and how severe these occur in TANGO2 patients.

However, as the Foundation notes, in all cases “the potential for rhabdomyolysis and life-threatening cardiac arrhythmia brought on by metabolic crisis is always there.”

The American Family Physician Journal defines rhabdomyolysis as a “potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation.” Cardiac arrhythmia means heart rhythm problems. And a metabolic crisis is defined as a “serious health condition caused by low blood sugar and the build-up of toxic substances in the blood.”

Neurodegeneration, “developmental delay, regression, and/or seizures” are also effects of TANGO2.

Today, all these terms roll off Kara’s and Matt’s tongues as if they were as simple and mundane as the ABCs, but back when they learned Bria had TANGO2, they had no idea what it really meant.

Turns out, the medical community didn’t either.

A diagnosis, but no understanding

David Skidmore, the medical geneticist at the Department of Pediatrics at Dalhousie University and the IWK, who had been caring for Bria since her first episode, tells the Examiner he was in Ontario on vacation when he got the news from the Netherlands, where Bria’s genetic testing was being done, that there was a diagnosis. She had a newly discovered disorder known as TANGO2.

The news evoked mixed feelings for him. On one hand, he felt relief that they had a diagnosis, although it was, he notes, “just a label” and not all that helpful as there was no expertise on how to deal with it.

However, Skidmore says, “I also felt a bit of frustration at the amount of blood I had taken out of this poor patient, trying to get a diagnosis, which in retrospect was completely unnecessary. Hindsight is always 20/20. But at least a diagnosis lets you stop worrying about what you’re missing.”

Skidmore points out that “ultra-rare diagnoses” such as TANGO2 don’t help doctors with clinical management. He notes that when the disorder was discovered, there were only a handful of documented patients, and half of them had already passed on while having an acute crisis.

Even today, Skidmore points out that most doctors are not familiar with TANGO2. “It’s one of 10,000 rare genetic diagnoses that never get taught,” he says. “This is the first case I’ve ever seen and probably the last case I’ll ever see, too.”

Skidmore says that even now the medical community knows very little about TANGO2:

We still have almost no understanding of the pathophysiology of TANGO2. We know what the gene vaguely does, but actually how it causes disease, we really don’t know. And we really still have no idea why it causes those occasional sudden deteriorations that seem to be mainly younger kids. There is all sorts of talk about how to manage it. But I don’t think anyone’s ever shown that the high glucose infusions that we suggest … is any true help; it’s just sort of a generic thing that we do, like many of our treatments.

Such poorly understood disorders are very hard on families and on patients, says Skidmore:

For many years, she was a child bouncing in out of hospital. I can’t remember if she got her last rights read to her, but she certainly merited it. Then all of a sudden she just got better by herself. So we don’t even know what made her better. How do we stop it from happening again? To this day, for TANGO2 that’s still the unanswered question. These [TANGO2] kids have usually only one or two of these strange episodes when their whole body basically shuts down … and they either get better or they don’t. We support them and cross our fingers and hope for the best. It’s terrifying for all.

Skidmore has enormous compassion and respect for the Dort family, how they have not only learned about the disorder, but also kept abreast of any new information available:

You have the poor family dealing with an ultra-rare diagnosis, which is brand new. After five or six hours of reading, you can almost become the world expert on it, because there are really probably less than 100 pages written about it. And again, every time I see the young patient, I do a quick literature search and see if there’s anything new. And every once in a while I find that something new is in the footnotes about TANGO2, and quite proudly say, “There was this poster at a conference in Europe that said this.” And the mom [Kara Dort] always goes, “Oh yeah, I got that six months ago.” She’s very much on top of things.”

Searching for a cure

The Dorts have not just been keeping abreast of TANGO2 research, they have also been active in the TANGO2 online community, sharing Bria’s story with other families around the world that are affected by TANGO2, and also raising funds for research.

Matt Dort says that they worked as a family to share the responsibilities. “We agreed that Kara would look after things like TANGO2 boards and committees while I would parent our children during those times when she was devoting time for those commitments,” he says.

“Kara is very intelligent and thrives in those areas, while I thrive at and prefer being a stay-at-home parent, making memories, and keeping our kids looked after,” adds Matt, whose love of the outdoors and fly-fishing — and generosity — made the news earlier this year when he quietly gifted a stranger he met on the Stewiacke River with a fishing rod.

Matt says that Bria’s illness has given him a new perspective on life and the world:

I realized that the true wealth, or a true miracle, is to have good health. And I understood and felt the pain that our family has faced from Braxton’s point of view, from Bria’s point of view, from Kara’s, mine, and our extended family’s of how difficult it was to be in such a medical crisis to a point where we almost lost Bria. And I felt that nothing matters anymore other than being healthy.

This was the impetus behind Matt’s involvement in the efforts to stop the Northern Pulp mill in Pictou County from pumping its effluent into the Northumberland Strait, when Pictou Landing First Nation and fishermen’s groups spearheaded the “No Pipe” movement in 2018 and 2019:

As I became more aware of what was unfolding with the pulp mill and the proposal, I realized it threatened the activities of my children’s well-being. I wanted to take them to the beach or go swimming or go fishing and all those things coming from the pulp mill, the pollution stuff, literally threatened that opportunity through air or water pollution. So I became passionate about that. And I wanted to try to make a difference and make people aware.

Matt, a registered sport-fishing guide, has raffled off several guided fly-fishing trips and related products to raise funds for TANGO2 research, and has raised more than $10,000 for the cause.

Early on, Kara Dort joined a small Facebook group of parents of children with TANGO2, which numbered about a half dozen when the disorder was first recognized, and eventually doubled in size.

Some of those parents founded the TANGO2 Research Foundation, which aims “to improve the lives of those children and young adults affected by TANGO2 related disease by helping to fund, coordinate and guide scientific research that leads to a better understanding of how TANGO2 mutations affect them.”

Kara, who is treasurer of the Foundation, says its members got to work immediately.

“We started committees and we started raising funds and applying for grants and really working hard towards a conference,” Kara says. “And then we held our very first TANGO2 conference in Houston, Texas. And that brought researchers from around the world and parents and patients from around the world. And we have this little family that grew from there, including Seema Lalani out of the Baylor Institute in Houston. She was the one who found TANGO2 because she had a patient, Sammy Lopez, who is since deceased. His photo is on our fridge.”

Kara didn’t stop there. She is now also on the IWK Foundation Board, and in the process of setting up a Canadian TANGO2 Foundation.

Kara says Bria’s condition has transformed her life, and her life’s mission is to help get a cure for TANGO2.

Discovering TANGO2

Seema Lalani, a professor of molecular and human genetics at the Baylor College of Medicine in Houston, is the lead author on the very first paper published about TANGO2, the only source of information on the disorder when Kara and Matt received Bria’s diagnosis five years ago.

In an email to the Halifax Examiner, Lalani says that two independent research groups discovered TANGO2 in 2016, one the Baylor College of Medicine in Texas, and the other in Germany.

“I was part of the Baylor study that reported 12 patients for the first time, who presented with multiple problems associated with TANGO2 deficiency including susceptibility to life-threatening cardiac arrhythmias,” says Lalani. “The discovery was made after carefully studying genetic variants in these patients who had exome sequencing completed.”

The exome is the total of all the genome’s exons, which are the coding portions of our genes. An organism’s genome is its complete set of genetic information.

Lalani says there have been several new studies since that initial discovery and paper about TANGO2, and it of utmost importance to understand how TANGO2 protein works before doctors can learn how to treat the disorder better.

At this point, Lalani says researchers are still trying to estimate the prevalence of TANGO2:

Recently, through the support of Chan Zuckerberg Initiative (CZI), the researchers involved with Rare Genomes Project at the Broad Institute were able to assess the prevalence of TANGO2 disorder. They estimated that the disorder is seen in approximately one in a million people, if we take all the world populations. However, in some populations such as non-Finnish Europeans, the prevalence can be as high as about one in 400,000.

And while TANGO2 is rare, with only Bria’s case so far diagnosed east of Montreal in Canada, Lalani says the disorder is found in many countries:

Through the TANGO2 Research Foundation, we are aware of at least 100 families who have been diagnosed. We have families from all over the world including Canada, USA, Netherlands, Germany, Italy, France, Australia, Saudi Arabia, and Mexico.

The diagnosis can be as simple as a single gene testing of TANGO2, or as comprehensive as whole exome sequencing where all 20,000 genes are queried. The testing is done by several commercial labs that specialize in genetic testing. They are located worldwide.

It is possible for people to learn their inherent genetic risks before they decide to get pregnant, says Lalani:

If both partners are found to be carriers, then there is a one in four chance for them to have an affected child. If both partners are carriers, prenatal testing can be offered to them.

However, for Lalani, right now the priority is to save the lives of children who have TANGO2:

Unfortunately, several of our families have lost children affected with TANGO2 deficiency due to life-threatening cardiac arrhythmias. We need to find better ways to treat and prevent cardiac arrhythmias and cardiac dysfunction in children. Once children have a metabolic/cardiac crisis, there is a higher chance of them having developmental regression. We need to find ways to prevent crises in children.

Living with the unknown

Bria is now seven years old, with the developmental level of a three-year-old.

Matt Dort says that the prospects for TANGO2 patients are unknown.

Bria’s story on the TANGO2 Research Foundation website sums up her health and life situation this way:

Bria has overcome so much. She still takes thyroid medication, a Mito Cocktail [a prescribed list] of supplements, and patches one eye every day for strengthening. Bria has cognitive delays. She babbles and has some words but has significant speech delays. Bria walks, but struggles with balance issues and gait abnormalities. Those are the medical pieces of Bria, which seem hard to believe when you meet her.

But, it says:

Bria as an individual is much more. She is funny and makes herself and others laugh frequently. She is full of life and has a beautiful way about her, both inside and out. She loves her pets (cat Singe and dogs Koda and Charlie) and her family, especially her brother Braxton and is extremely engaged when meeting new people. She studies those around her and works very hard to overcome her challenges daily. Bria takes therapeutic horse riding lessons and it has helped her to walk and build her confidence.

COVID-19 has been particularly difficult for the family. Kara explains that Bria can’t keep the mask on, as she has sensory issues with anything on her head and face.

“We didn’t enter a store for an entire year,” says Kara. Groceries had to be delivered to the house, and no one was allowed to enter to protect Bria, who still needs to be watched very closely all the time.

“If she vomits, she has to go directly on a special IV,” says Kara.

“Not easy” for anyone

These days, Kara’s mother, Donna Cameron, looks after Bria and Braxton while their parents are at work.

Donna, who lives about 15 minutes from the Dort home, says she is also the caregiver for her 97-year-old mother who lives with her.

She says that with COVID restrictions easing, Bria can go to school for two hours a day three days a week, depending on her energy levels. Still, they keep her in a play area on her own, to be cautious. Donna has only praise for the early intervention program in Pictou County,[2] and the case worker who looks after Bria, whom Donna describes as “above and beyond” wonderful.

When she’s not at school, Donna says Bria’s days centre around music.

“If anything happens, you can calm her down with songs, make her happy with music,” says Donna. Even when occupational therapists are working with Bria, without music she gets bored and doesn’t respond.

Donna says Bria is “very, very good at expressing her needs and wants.” She will stand in front of the speaker and say “on” until someone gets Alexa [the voice command on their device] to play what she wants:

She sings along, she has her playlist. Alexa has been wonderful. It’s on all day. Poor Braxton. It’s the bane of his existence, because he has to hear the same songs all the time.

Although her vocabulary is still quite limited, Donna says it is expanding, and Bria does have friends from school.

Donna keeps a close eye on Bria’s gait and posture, as one sign of a pending health crisis is when she tilts her head. They also keep Bria on a strict diet to keep her bowels happy, as any intestinal issues are an indicator of bad things to come.

As much as the family appears to be managing the stress that TANGO2 has put on their lives, Donna says Kara and Matt may have been “sugar-coating” the story a little for the Examiner, and that it’s not been at all easy for anyone, especially not at the beginning.

“I saw two wonderful people, who never had a night’s sleep. My daughter might have weighed 90 pounds soaking wet, lost all her hair, had black circles down to here,” she says, pointing to her neck and tearing up as she speaks. “She was very downtrodden, very withdrawn, and she looked like, oh, the walking dead.”*

Donna continues:

The most sleep I think either of them had even for their first year back to work might have been two hours. Bria has not slept one night without one or the other in her bed with her. Whatever you know about relationships, [you know] how difficult [this is]. There was no going out with their friends. When they were together with friends, they … can’t be in the conversation or doing anything because they have a special needs child that they can’t take their eyes off. Ever.

Donna says there were also financial pressures back then, and, of course, Kara and Matt had another child — Braxton — who before Bria had her first episode, had never spent a day away from his mother or father.

“And all of a sudden mommy and daddy were gone,” says Donna. She didn’t like to take him too often to the hospital, where she would have to explain to him that his parents couldn’t come home that night. She says Kara and Matt did their best to take turns at the hospital so they could each spend time with Braxton.

But, she adds, “It was a challenge. He was excellent. I think he was a little tired of having his Nanny.”

“Braxton and Matthew and Kara as a family were very strong, and I’m very, very proud of them,” says Donna.

Another book for Bria?

Braxton says that he intends to keep selling his book about Bria to continue raising money for research into TANGO2, and he might even write a sequel to it.

He says he would like to write another book about her life, maybe a funnier one that is also “heartfelt and sad.”

Braxton says there is much he would like the world to know about his sister:

I know that most kids might just think, “Oh, she’s weird, she’s silly, she’s stupid.” … She tries her best and she can’t do everything she tries to do. So I think she deserves a lot more respect, because if I were to be Bria, I would be a lot more frustrated at myself and I would take things a lot harder, like when she falls and she can’t talk, and she’s really upset because she can’t do things like that. Sometimes it’s just putting your own self in her shoes, see what she really feels.

Asked if Bria’s TANGO2 made him look at life differently, Braxton says:

I always believe that you should always try to make friends with, say, people that don’t have as easy a life as you do … I believe you should make friends with people who need friends, not people that have a lot of friends. Like somebody else in her class might say, “Oh, Bria, why can’t you do this or why can’t you do that?” Well, she’s trying to do “this” and “that.”

Braxton says he doesn’t yet know what he would like to do when he grows up, but one thing he doesn’t intend to be is a TANGO2 researcher.

Asked why not, Braxton replies, “When I’m that age, I hope they’ll already have a cure.”

* This quote has been slightly modified at the request of the family.

Endnotes

[1] “How do you solve a problem like Maria?” is a show tune from the 1959 Rodgers and Hammerstein musical, The Sound of Music,” later turned into a popular film.

[2] The full name of the provincial program is Nova Scotia Early Childhood Development Intervention Services (NSECDIS).

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