SINGAPORE: Meet Cooper Jarrott. He’s 19, genial, a Lego whizz, a video games master, and a young man with an infectious streak of enthusiasm. “I’m smart, I’m intelligent and creative,” he says with a proud grin when asked to describe himself. He’s also a keen, if belated, food lover; butter chicken, pizza and pasta topping his favourites list.

But Cooper can also be awkwardly spoken. He’s only just tackling the challenges of independence, learning to take the train from his home in outer Melbourne to the suburban TAFE course where he’s adding to his list of life skills. He has a tendency towards anxiety. And he’s closer than most to the definition of unique.

For almost every day of his two decades he has stood out. His ears low-set and pointy, he was late to talk, to walk and to interact. Although he has eventually met many milestones, he’s seemingly chased them forever, the rhythm of his personal development unlike anyone his family has encountered.

“It’s just Cooper being Cooper,” has become the mantra of his loving parents, Leanne and Ken, and sister Kayley. Still, through long years of tests and therapies, and even as his differences grew, no one could solve one lingering and supposedly simple question: What exactly was up with Cooper?

And even when an answer finally, and miraculously, arrived, it did not wrap up his rollercoaster story with its equal parts of love and mystery. Because, as his family has also discovered, an answer is not always a solution.

“He was a really happy baby. Very happy.” Leanne Jarrott speaks with adoration and warmth about the late days of 2006 when her second-born came into the world. She’s a vivacious woman, highly organised; a neat, packed file documenting her son’s medical journey sitting on the dining table of her outer Melbourne home. Cooper, mostly quiet except for an occasional chuckle, is beside her.

Three years before his birth, his sister Kayley had breezed through the earliest months of her life, setting the benchmark by which many parents assess the progress of future offspring. So when, at six months, Leanne noticed that Cooper, otherwise giggling and smiling, would stiffen, clenching his fists, his feet straight, she was disconcerted.

“He wasn’t moving like a baby should,” she says now, recalling how her son made no effort to reach for his toes, to grab a toy or try to roll over as he grew. “Because he was my second child you knew what milestones he was going to be (hitting). And he wasn’t.”

A child health nurse wasn’t worried initially. “He’s just a bit young,” she advised, “and maybe a bit slower than normal.” But by the next visit, when Cooper was also rejecting all food bar breast milk, she recommended specialist help.

In the second half of his first year, Cooper began occupational and speech therapy – the first of interminable treatments that would outlast his childhood – and he was assessed by physiotherapists and psychologists.

But even with all those interventions, and being referred to a genetics expert, the absence of explanations persisted. Why was he not eating? Why did he often dribble and flinch involuntarily? Not speak for years? Observe more than interact? Why was his body floppy?

Everyone is unique but Cooper’s differences, when combined, seemed inexplicable.

“It was always in the back of your mind,” says Leanne. “Why can’t we find out what’s wrong? But his pediatricians over the years said ‘He’s just him. And at this stage we don’t have the answers’.”

The cause, experts advised, was likely to be genetic. But even in the first decade of the 21st century technology could only provide so many answers as Cooper underwent tests for Down syndrome and cerebral palsy, for autism and Asperger’s. He had scoliosis X-rays and, aged one, underwent his first genetic test. But the results were invariably negative – while he ticked some boxes on some tests, “he wasn’t ticking all the boxes for anything” – setting the frustrating, irreconcilable tone his parents would encounter for years.

“It was so intense,” says Leanne, who abandoned plans to return to her former position in administration sales. “With all the appointments we had for him with therapies, I couldn’t work, and then we were given all these exercises to do on a daily basis: to teach him how to crawl, to try and get him to eat, little things like pushing his knees under his tummy.”

The therapies helped. Cooper started to babble, said his first word (“Mum”) at three and was talking by five. He was encouraged to suck on a piece of rubber to become accustomed to the sensation of chewing, and eventually he began to eat.

As he approached school age, there was still a gap between Cooper and most of his contemporaries, but father Ken, for one, was hanging on to the belief that he would catch up eventually and attend a mainstream school.

Yet other issues kept arising. Cooper became anxious often, and his frustration would manifest as aggression. “His anxiety would build up and when he let it out just all hell broke loose. His thing was to be aggressive, so he would pinch and kick,” says Leanne, who eventually installed a gate in the family kitchen. “My daughter and I used to stand in there, while he had a reset, to protect ourselves.”

Cooper would go almost nowhere without his mother, who, in between near constant care, therapies and exercises, was also batting away regularly questions about her son’s condition.

“I said he had a broad diagnosis of intellectual disability. And then they’d go, ‘So what’s wrong with him?’.” It happened regularly: among friends and family, at the potential kindergarten where she revealed Cooper’s broad but unspecified diagnosis that at the age of two meant he was the intellectual equivalent of a nine-month-old. “And they said ‘What does that mean? What exactly is it?’. That ended in tears,” she says. “People just don’t get it if you don’t have an answer. They just couldn’t let Cooper be Cooper.”

Mainstream education did not happen. He attended a special primary school and another for high school until he was 17, learning drama, music and maths, but also life skills such as cleaning and washing and cooking. Still his undiagnosed intellectual condition led to other obstacles.

“He didn’t get invited to birthday parties. You couldn’t just drop him at a friend’s place and leave. One grandparent said ‘I can’t take them both; I’ll look after Kayley and not the other’.” So many times he was excluded or, on the verge of a meltdown, was whisked away. “It would often be me with him,” says Leanne, “and the rest of the world going on.”

Being Cooper’s mother was a point of pride, but also keenly challenging. “It’s like a grieving process. Because you’ve got your baby, your child, it’s exciting, then things start to change. And you realise what you thought was going to be your life is not your life.”

There was also the worry, and guilt, that whatever was happening to Cooper was hereditary. And there were the different facets of Cooper: explosive sometimes, he was also the boy who, when he learned to talk, would turn to his mother, just minutes after he’d unleashed another round of fury, and say simply, “Sorry”.

So, yes, Leanne was irked by the incessant snooping and probing. But she also had no answer.

The isolation experienced by Cooper’s family was intense. But, ironically, it was not unusual. “One of the biggest challenges that families face when they have a child who has a rare disease is not being able to get the initial answer of what’s going on,” says Professor John Christodoulou, chair in genomic medicine at Melbourne’s Murdoch Children’s Research Institute.

He understands well the years-long diagnostic odysseys, punctured by silences and solitude, that families such as Cooper’s experience. Trained as a pediatrician, Christodoulou for decades has worked with those confronting rare diseases. Thirty years ago he turned to genetics, a move that would have unimaginable consequences for Cooper’s family.

They were deep in tests and therapies, and seemingly moving nowhere closer to an answer when, in 2012, Christodoulou was approached by a young student from the Netherlands. In her mid-20s, Lot Snijders Blok was keen to expand her understanding of the burgeoning world of genetics.

That year she spent six months interning with Christodoulou at The Children’s Hospital at Westmead, Sydney, using laser-based technology to analyse cells in metabolic diseases caused by genetic variants.

“I definitely enjoyed my internship in Australia,” says Snijders Blok, now a renowned clinical geneticist. “I learned a lot about genetics in the laboratory there. I came as a medical student and left as someone who wanted to do research instead of patient care.”

She returned to Sydney to work with Christodoulou again for three months, before heading home. In early 2016, she began her PhD studies in the Netherlands.

By then, technology had improved further. Even compared to her recent time in Australia, it was sharper and more focused, providing researchers with even closer views of genetic coding. For her doctoral thesis, Snijders Blok harnessed this ever-refining technology and used it to examine children with unsolved development disorders, many with speech difficulties.

During the two years of research that followed, she came across a variant in a seemingly important gene. POU3F3, also called Brain-1, was known to be involved in the development of the central nervous system. “Its purpose seems to be to control other genes to turn on or off,” Snijders Blok says from her home in the Netherlands. But until 2019, it had not been associated with a neurodevelopmental disorder.

What Snijders Blok saw suggested it now might be. “If you have a problem with this gene, then the switching on or off of other genes does not go well,” says Snijders Blok, who later accessed GeneMatcher, a Tinder-like database of case information obtained by other researchers, and was able to detect more cases.

The variant, she concluded, appeared to occur spontaneously and was not likely to be hereditary. Its appearance, it seemed, was down to bad luck.

By the time her co-authored work was published in the American Journal of Human Genetics in 2019 – outlining a range of common factors including speech delays, intellectual disability, low muscle tone and low-set, sometimes cupped ears – she had details of just 19 cases around the world of a new and rare neurodevelopmental disorder.

It would soon be co-named in her honour: Snijders Blok-Fisher syndrome.

That same year, Leanne Jarrott was nearing despair. Cooper had been attending appointments at the Murdoch Children’s Research Institute since 2007. He had undergone exhaustive genetic tests. But still an answer was elusive, and for a time it seemed no further tests were even available.

Then in July 2019, at the suggestion of Cooper’s pediatrician, Leanne and Ken penned a letter to the Victorian Clinical Genetics Services pleading for Cooper’s inclusion in a whole exome chromosome test, using the latest technology to read his genetic code.

“It has been a source of great frustration for a family like ours to not have answers to the many questions pertaining to their child’s difficulties. These frustrations are not getting any easier now that our son is getting older,” the couple wrote. “In the absence of this understanding, we worry incessantly about his future.”

Cooper’s diagnosis of intellectual disability, they said, “has always proven to be inadequate in explaining many aspects to how he presents and the difficulties he experiences. We (and other professionals) have long felt there is a missing genetic piece to the picture and this missing piece means that Cooper is often not understood or given the support he requires. As a result of this lack of understanding our family is significantly challenged and we cannot communicate more profusely how desperate we are for answers.”

When the letter arrived at the VCGS office on the other side of Melbourne, Dr Natasha Brown was deeply moved. “That just touched my heart,” says Brown, a clinical geneticist who, over many years working with families facing enormous medical challenges, had never received a note from imploring parents. “We took the case to our meeting and said ‘Obviously he meets the funding criteria for our tests’.”

Using blood samples, Cooper had his first genomic test in 2019. With the best sequencing technology available, the results still took more than half a year to be produced – and again came back negative. “We couldn’t identify a plausible genetic change in any of the known genes at that time,” says Brown, as the endless lull continued.

Over the following years researchers reviewed Cooper’s data periodically, combing through it for genetic variants. When still nothing was found, in late 2021 his case was referred to the newly established Rare Disease Now, a Melbourne-based organisation that searches for answers when children remain undiagnosed even after substantial clinical investigations.

“We’ve done a whole range of different techniques,” says Dr Michelle de Silva, RDNow’s program manager. “We relooked at his clinical information. We did some whole genome sequencing. And when nothing was found we went to a long read. And that was the one that made all the difference.”

By then, the pace of technological advances seemed to be surpassing itself every year. “We’re discovering more genes faster and faster,” says de Silva, who, when completing her PhD in the late 1990s, spent three years trying to identify one gene variant. “We could do that now in a day.”

In late 2023, using technology that had not been available when Cooper was first referred to RDNow just a year or so earlier, samples of DNA extracted from his blood were tested with DNA samples from his parents, first by machine and then by teams of highly skilled genetics experts. They were searching for tiny spots where Cooper’s DNA was unlike his parent’s.

“We all have changes in our code that’s different from our parents and that makes us unique. Most of them are innocent differences that don’t change the way we develop,” says de Silva. Now specialists were on the lookout for more suspicious changes – “something that’s sitting in a gene that could have an impact on the instructions of how that gene works”.

Leanne was expecting little as she headed to a meeting at the VCGS inner-city office in October last year. “Every 12 months or two years, they would say ‘We would like to have a chat’.” After so long, a pattern of kindness muddled with disappointment had formed, and this time she was so underwhelmed at what may ensue that she and Cooper, without Ken, headed to meet clinical geneticist Natasha Brown.

And then this happened. “I said, ‘We’ve got an answer’,” Brown recalls of that life-altering moment. After 18 years of uncertainty “all the pieces of the puzzle came together”, and researchers had a diagnosis for Cooper.

Leanne, shocked, burst into tears. “I was taken aback,” she says now. “I was worried about what they had found. I was emotional; I cried. Cooper said ‘What are you crying for, Mum?’. And they gave me the name of it, and they said ‘Don’t worry, it’s not going to mean anything to you’.”

Shortly before his 19th birthday, Cooper – the young man whose life had been punctured by missed markers – achieved two deeply significant milestones. He became the first person in Australia diagnosed with Snijders Blok-Fisher syndrome, and the first to be diagnosed with a rare genetic condition using long-read whole-genome sequencing.

His response? “It’s pretty cool.”

For Cooper’s mother, the news was mixed. “Relieved that it probably wasn’t going to be something that was going to take him, in a sense,” says Leanne. And having a name helped enormously. “You know what you’re dealing with.”

But it was also belated confirmation that this sort of life was indeed long-term.

“You live in hope that you’re just going to catch up somewhere. You know you’re not. But you’re just looking for that little miracle,” says Leanne of her family’s pre-diagnosis life.

Confirmation brought a double-edge certainty. “It’s not going to get any better. And if it is this rare, no one’s going to know about it. So we’re still back to square one in a sense; now you’ve got to go through and explain it to people again.”

While dozens more cases of Snijders Blok-Fisher syndrome have since been identified internationally, no one of a significant age has been diagnosed and so no one can describe the future to Cooper or his family.

The researcher who found the answer to Cooper’s long-unsolved question is far from morose. “There’s no reason to think that POU3F3 is progressive,” says Snijders Blok, who is just 38. “It’s a developmental disorder where you’re born with a brain that’s wired in a different way, but there’s room for development – and no reason to think that there is some kind of downhill (decline).”

For those who love Cooper, the future now has a name but not yet an outline. In the six months since Cooper’s diagnosis, his parents have become even more diligent about his physical activity and caring for his body, even though the path ahead remains unclear.

So they continue to focus on what – and who – they have: a Lego-loving son and brother who continues to hit markers. “He’s walking around. He goes out. He does things. Yes, he’s going to have his challenges as well,” says Leanne, who, in the months since the diagnosis, has clung to the small sheaf of papers she was handed back in October, among them Snijders Blok’s original journal article.

Cooper at 19 is a happy young man. “He can communicate. He has some sensory issues. He can be a little bit controlling,” says his mother. “He can’t get words out. Giving directions, you have to break it down so you can’t give him more than three directions at once to do something. He can dress himself but showering he still needs help.”

He still requires supervision and he can still become anxious if he’s unsure or in a new situation. But still those milestones keep arriving. And, even belatedly, he keeps tackling them.

“First time ever,” says Leanne, “a few weeks ago Cooper goes ‘Can you take me to Knox City (shopping centre) on Saturday?’.” For the first time, he was meeting friends for an outing on his own.

Of course she said yes. And for the briefest moment, she also allowed herself a little cry.

Happy tears.