Achieving a greater understanding of autism

Australian and Chilean scientists have made a breakthrough in their understanding of the genetics of a common form of autism, while others are calling for the term “high-functioning autism” to be consigned to history.

The Murdoch Children’s Research Institute (MCRI) led research focusing on genes linked to Fragile X syndrome (FXS), one of the most common genetic causes of intellectual disability and autism spectrum disorder (ASD), particularly in boys. Published in the journal Molecular Autism, their research could one day lead to the development of treatments for the condition.

The international study looked at 100 children, adolescents and adults — half in Australia and half in Chile — with Fragile X, caused by a disruption to a single gene known as FMR1. This disruption was previously thought to occur almost exclusively through presence of a repeated DNA sequence, called ‘full mutation’, that makes the gene inactive.

“Within our study group of people with FXS, the gene, FMR1, was completely turned off in some, while in the majority of participants it was partially turned on,” said Dr Emma Baker from the MCRI. “The gene, FMR1, is totally turned on in people without Fragile X syndrome, and so it would be fair to expect that people with the partially turned on gene would have less traits of autism, but we found the opposite.

“Unexpectedly, we showed for the first time that people with a partially turned on FMR1 had intellectual disability and more traits of autism spectrum disorder, whereas people with the gene completely turned off had intellectual disability and much less severe autism. This is possibly because the genetic code of the FMR1 gene in FXS is not the same as in unaffected people.

“In FXS the gene contains a large repetitive sequence called full mutation. When this full mutation is turned on, it may cause autism features worse in FXS. These findings are significant because they enhance our understanding of the biology of autism, and may explain why severity of Fragile X is not the same between affected individuals.”

MCRI’s Associate Professor David Godler, a senior researcher in the study, said global pharmaceutical companies have invested millions of dollars trying to develop medications to treat autism and often use Fragile X syndrome as their model.

“In mice these targeted drugs were very effective, but have failed in most human trials,” he said. “This may be due to the fact that in mice, the FMR1 gene is artificially completely switched off, which is not consistent with the biology of the majority of males with Fragile X as shown in this study.

“Our breakthrough may explain why trials for drugs treating autism have to date not worked and it may enable researchers in future trials to separate people into those with partially turned on FMR1 and those with FMR1 turned off.”

Dr Baker hopes the study will have an impact on the development of treatments and interventions aimed at improving behaviour in individuals with Fragile X. She said, “I want the ultimate result of this research to lead to a better quality of life for both the affected individual and the families who support them.”

The study comes as autism researchers from the Telethon Kids Institute have called for the term “high-functioning autism” to be abandoned, due to the misleading and potentially harmful expectations it creates around the abilities of children on the autism spectrum.

Writing in the journal Autism, a team led by Dr Gail Alvares noted that the term was first coined by researchers in the 1980s as a descriptor for people who had autism but did not have an intellectual disability. It is based purely on an IQ assessment, Dr Alvares said, rather than a functional assessment — “yet somehow has crept into everyday use and has come to imply that people can manage perfectly fine, and don’t experience any everyday challenges”.

Dr Alvares said that for many individuals with autism spectrum disorder, this couldn’t be further from the truth. “A lot of children and young people with autism may have an appropriate IQ for their age but still struggle with everyday skills like getting themselves to school, navigating public transport or communicating at the same level as their peers,” she said.

“How well you function is not about your IQ, but about how well you’re able to perform in your environmental context, for your age.”

The researchers reviewed data for 2225 children and young people (aged 1–18) diagnosed with autism, about half of whom had intellectual disability and half of whom did not. They found those with an intellectual disability had functional skills which closely matched their reported IQ; however, those typically deemed to be “high functioning” due to having an average or higher IQ had functional abilities well below what would be expected.

“We demonstrated that those who didn’t have intellectual disability — what people would have classically called ‘high-functioning autism’ — in fact have marked challenges with their everyday skills compared to what we would typically expect from their IQ,” Dr Alvares said.

Dr Alvares said deeming someone as high-functioning based on IQ alone not only creates false expectations about a person’s abilities, it also exposes them to disadvantage.

“It might be used, for example, to argue that a child should be able to go to a mainstream school without support when, in fact, while they may perform well on cognitive assessments, they still struggle with skills like understanding instructions, note-taking, self-care, changes to routine or interacting with their peers,” she said.

“By continuing to use this term, we may be inadvertently perpetuating a cycle that denies people access to services and support that they need based solely on their IQ.”

Dr Alvares said the study thus demonstrates why the phrase high-functioning autism should be dropped, as has been suggested by the growing global movement to change the language around autism. The results also highlight the need for comprehensive diagnostic evaluations that incorporate functional assessments, to guide service provision and funding allocation.

“If we’re not doing appropriate assessments at the time of diagnosis, to understand what a person’s strengths and challenges are so we can provide appropriate support, individuals are at risk of falling further and further behind their peers,” Dr Alvares said.

Image credit: ©stock.adobe.com/au/dobova

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