If you’ve met one person with autism, the saying goes, you’ve met one person with autism.

This popular quote attributed to autism expert Dr. Stephen Shore captures a truth that has long challenged researchers, clinicians, and families: autism spectrum disorder (ASD) is not one thing, but many. It’s even in the name — “spectrum”. Some children speak early and struggle with social nuance, while others don’t speak at all. Some excel in math but can’t handle loud noises. But the label “spectrum” often falls short, hinting at a neat continuum when the reality is far messier.

Now, a new study may provide some clarity. A team led by researchers at Princeton University and the Simons Foundation has identified four distinct subtypes of autism—each with its own behavioral fingerprint and underlying genetic profile.

“This helps explain why past genetic studies often fell short—it was like trying to solve a jigsaw puzzle without realizing we were actually looking at multiple different puzzles mixed together,” said Natalie Sauerwald, co-lead author and associate research scientist at the Flatiron Institute.

A Data-Driven Mosaic

Rather than searching for a single cause or gene, the team embraced the diversity of autism from the start. They analyzed behavioral and genetic data from 5,392 autistic children in the SPARK cohort, a nationwide study funded by the Simons Foundation. Using a statistical approach known as generative finite mixture modeling, they sifted through 239 traits—ranging from language milestones to anxiety symptoms—to group children by their overall patterns of development.

Four distinct clusters emerged.

Each group reflected a different trajectory through childhood. Some children showed few delays but high social anxiety. Others had profound developmental impairments from early on. What set this study apart was not just the nuance in behavioral patterns—but the discovery that each subtype came with a unique genetic signature.

The Four Faces of Autism

The largest group, called Social and Behavioral Challenges, included about 37% of the participants. These children generally hit developmental milestones on time but had pronounced difficulties with social interactions and repetitive behaviors. They also showed high rates of co-occurring conditions like ADHD, anxiety, and depression. Doctors often diagnosed children in this group later than others.

The second group, Mixed ASD with Developmental Delay, made up 19% of the cohort. These children experienced early delays in walking, speaking, or other milestones, but did not typically exhibit disruptive behavior or mood disorders. Interestingly, their genetic profile showed a mix of inherited rare variants and new (de novo) mutations—suggesting a subtler, perhaps more inherited pathway to autism.

A third group, Moderate Challenges, included 34% of the children. These individuals exhibited fewer core autism traits and had no major developmental delays. They also had the lowest rates of psychiatric comorbidities. Genetically, they had more rare mutations in genes that aren’t as crucial for basic development—mutations that may cause subtle effects rather than severe ones.

Finally, a small but striking group (about 10%) stood out as Broadly Affected. These children faced severe challenges across the board: early developmental delays, social and communication difficulties, repetitive behaviors, and co-occurring psychiatric diagnoses like depression and mood dysregulation. Genetically, this group carried the greatest burden of high-impact de novo mutations, especially in genes critical for brain development.

When Genes and Development Align

One of the most compelling findings in the study was how closely gene activity aligned with each subtype’s developmental trajectory.

In the Broadly Affected and Mixed ASD with Developmental Delay groups, the mutated genes tended to be expressed during prenatal development. This tracks with their early onset of symptoms and delays in basic milestones.

By contrast, in the Social and Behavioral Challenges group, the affected genes were mostly switched on after birth, especially during childhood and adolescence. These children reached milestones like walking and talking on time, but struggled as social demands grew more complex.

Even within the brain, the subtypes diverged. For example, children in the Social and Behavioral group had disruptions in genes tied to inhibitory neurons in a specific region of the developing brain, the medial ganglionic eminence. Meanwhile, those in the Mixed ASD with DD group showed changes across a broader set of brain cell types.

Rewriting the Diagnostic Playbook?

Autism research has long grappled with the “one size fits all” problem. For years, scientists tried to find single genes that could explain autism—or at least large portions of it. But the condition has stubbornly resisted such reduction.

“Despite autism being 60 to 80% heritable, it’s hard to pin down a specific genetic cause for any one individual,” co-lead author Aviya Litman, a graduate student at Princeton, explained to Scientific American. “[Until now] the cause is only clear for about 20% of autistic people tested.”

This study doesn’t solve that entirely but it pushes the field closer to precision. By focusing on phenotypic subtypes rather than isolated traits, the researchers were able to uncover distinct biological pathways. Each group had different types of mutations—some inherited, some de novo—and each group’s affected genes disrupted different cellular processes.

The findings also held up in a separate dataset (the Simons Simplex Collection), further bolstering their validity.

Catherine Lord, a psychologist at UCLA not involved in the study, said the groupings “make sense and follow lots of findings by other researchers.” What’s new, she added, is “the connection to genetics that makes these results most noteworthy,” as per Scientific American.

A Tool for the Future—With Caveats

For now, this research is not ready to be used in clinics. The study sample was mostly white, and some genetic results could only be calculated for children of European ancestry. Autism is highly diverse, and many traits—especially those in underrepresented populations—may not have been captured.

“This classification is not a definitive, comprehensive grouping,” said Olga Troyanskaya, senior author and professor of genomics at Princeton. “With additional data, more precise definitions of subtypes could emerge.”

For clinicians, subtyping could one day guide diagnosis and tailored therapies. For families, it could provide clarity—and perhaps relief—by explaining why their child’s path seems different from others with the same diagnosis.

And for researchers, it may finally offer a roadmap to untangle autism’s daunting complexity.

The findings appeared in the journal Nature Genetics.