Autism is now widely understood to have a strong genetic basis, yet for decades, researchers struggled to pinpoint exactly how genes shape the condition. 

New findings are gradually shedding light on why autism develops in some people, revealing a complex interplay of rare mutations, common genetic variants and environmental influences.

This report is based on a recent in-depth article by the BBC, which examined how modern genetics is transforming scientific understanding of autism and reigniting debates within the autistic community about identity, disability and treatment.

Until the late 20th century, autism was often wrongly attributed to parenting. In the 1940s, Austrian psychiatrist Leo Kanner proposed the now-discredited “refrigerator mother” theory, suggesting autism resulted from emotional coldness in mothers. Daniel Geschwind, a professor of neuroscience and genetics at the University of California, Los Angeles (UCLA), says this idea was “deeply damaging and wrong”, yet it took decades to overturn.

A turning point came in 1977, when researchers showed that autism frequently occurs in identical twins. That study provided the first strong evidence of a genetic component. Subsequent research has shown that if one identical twin is autistic, the likelihood that the other twin is also autistic can exceed 90%. For fraternal twins of the same sex, the figure is about 34%, far higher than the general population rate of roughly 2.8%.

From single genes to thousands of variants

Scientists now agree that genetics plays a central role in autism, but the picture is far from simple. Between any two people, around 0.1% of DNA differs. “Sometimes these variations have no effect at all,” says Thomas Bourgeron, a neuroscience professor at the Institut Pasteur in Paris. “Sometimes they have a little effect, and sometimes they have a super strong effect.”

So-called “super strong” genetic changes have been identified in up to 20% of autism cases. These involve a single mutation in a single gene that can profoundly disrupt brain development, often leading to severe disability. “This is not like the autism you see in the movies,” Bourgeron says. “If you’re born with one of these major mutations, there’s a high likelihood you’ll end up with intellectual disability or motor delay [the ability to coordinate muscle groups] or epileptic encephalopathy.”

More than 100 genes have now been linked to such mutations. Bourgeron was among the first to identify autism-related gene changes in 2003, showing that they affected proteins involved in synaptogenesis – the formation of connections between neurons.

Some of these mutations arise spontaneously in embryos and are not inherited from either parent. Geschwind likens these so-called de novo variants to a “bolt of lightning”. In other cases, a parent may carry the same mutation without being autistic themselves. “What seems to happen is that in the parent, it’s not sufficient to be causal, but in the child, that major gene mutation combines additively with other, less individually impactful gene variants to drive neurodevelopment differences,” Geschwind explains.

Environment still matters

Genes do not tell the whole story. Even among identical twins, one may be autistic while the other is not. Researchers believe environmental factors also play a role, although past efforts to identify them have sometimes fuelled misinformation, including discredited claims linking autism to vaccines.

According to the US National Institutes of Health, potential non-genetic contributors include prenatal exposure to air pollution or pesticides, extreme prematurity, and complications at birth that reduce oxygen supply to the brain.

Early brain development

Many autism-linked genes become active during early foetal brain development, particularly in the formation of the cortex, which governs higher functions such as memory and reasoning. This critical period peaks between 12 and 24 weeks of pregnancy.

“You can think of these mutations as disrupting the normal patterns of development, knocking development off of its normal track so to speak and maybe onto another tributary, instead of the normal, neurotypical pattern of development,” says Geschwind.

For families affected by rare mutations, genetic insights can be invaluable. They can help parents understand future risks and connect with support networks such as the FamilieSCN2A Foundation. “We can also give the family a sense of the spectrum of how their child might develop over time,” Geschwind says.

Identity, ethics and concern

Not everyone views genetic research on autism positively. Autism spans a broad spectrum, from individuals with profound disabilities requiring lifelong care to those who see autism as a core part of their identity. Some fear that genetic research could lead to prenatal testing and selective termination.

“Autism isn’t a biological phenomenon that has to be tested for, and where you get a categorical outcome or prognosis,” says Sue Fletcher-Watson, professor of developmental psychology at the University of Edinburgh. “It isn’t something, like cancer, that is universally agreed to be bad and for which everyone wants a cure. In my opinion, it never will be.”

She warns that political contexts and historical examples of eugenics heighten fears about the misuse of genetic data.

A spectrum within the spectrum

Other researchers argue that genetic research is essential, particularly for those at the most severe end of the spectrum. Joseph Buxbaum, a psychiatry professor at the Icahn School of Medicine at Mount Sinai, points to autistic people with no language and significant intellectual disability. “When I think about interventions, I’m thinking about these people,” he says.

To better describe this group, the term “profound autism” was formally recognised in 2021. Since then, clinical trials have begun to target specific gene mutations. 

One approach focuses on boosting the unaffected copy of a gene when only one copy is damaged. “That means you have one unaffected copy, [the activity of which] which we showed could be turned up to compensate,” says Geschwind.

Trials are also exploring gene therapy. The US Food and Drug Administration has approved a study by Jaguar Gene Therapy involving children with mutations in the Shank3 gene. Such trials rely on years of genetic and developmental research. “This trial is only possible because all the children participating have genetic diagnoses,” Buxbaum says.

Where science and society meet

Critics caution against framing these advances as “cures” for autism. Fletcher-Watson argues that many single-gene cases represent intellectual disability rather than autism alone, and that research priorities can be skewed by funding and advocacy dynamics.

At the same time, researchers see promise in using genetics to treat conditions that often accompany autism, such as epilepsy, sleep disorders and gastrointestinal problems.

Bourgeron, who now works closely with autistic people and their families in European research projects, says the ultimate goal should be inclusion as well as science. “Overall, we need to do a better job of recognising neurodiversity, and doing everything we can to make sure that people who function differently from the majority can flourish in our societies.”