Four Autism Subtypes Found in Study of 5,000 Children
These subtypes represent different clinical presentations and outcomes.
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New research from Princeton University and the Simons Foundation suggests that the neurodevelopmental condition autism spectrum disorder (ASD) has four distinct subtypes: social and behavioral challenges, mixed ASD with developmental delay, moderate challenges and broadly affected.
“These findings are powerful because the classes represent different clinical presentations and outcomes, and critically we were able to connect them to distinct underlying biology,” Aviya Litman, PhD student at Princeton and co-lead author, said.
The study is published in Nature Genetics.
Mapping autism phenotypes with genetic data
An estimated 1 in 100 children have ASD globally, according to the World Health Organization. While some characteristics of the neurodevelopmental condition might be detected in early childhood, ASD is typically not diagnosed until later in life.
Individuals with ASD have varying needs that often change over time, which can make it difficult to provide suitable and effective care. What’s more, the causes of the condition are complex – most scientific research points to a combination of genetic and environmental factors being at play, compounding these challenges further.
Clinicians and researchers have sought ways to define subtypes of ASD to help the process of diagnosis and treatment, if necessary. Despite progress in uncovering ASD-related genes, a unified map connecting genetic variation to clinical phenotypes is still lacking. The new study builds on over a decade of ASD genomics research by co-lead author Professor Olga G. Troyanskaya and colleagues, leveraging phenotypic data from over 5,000 children enrolled in SPARK – an ASD cohort study – to address this gap.
The research team used computational modeling to analyze the SPARK data, in combination with matched genetics, to identify clinically relevant classes of ASD and their patterns of both core, associated and co-occurring traits. They classed this as a “person-centered” approach as it considered over 230 traits in each person, rather than linking genetic associations with single traits.
“By integrating genetic and clinical data at scale, we can now begin to map the trajectory of autism from biological mechanisms to clinical presentation,” said Dr. Chandra Theesfeld, senior academic research manager at the Lewis-Sigler Institute and Princeton Precision Health, and study co-author.
Four subtypes of ASD have been identified
The four subtypes identified by the study include:
- Social and behavioral challenges: Individuals in this category present with core social challenges and repetitive behaviors – core autism traits – but reach developmental milestones at the same pace as children without autism. Approximately 37% of the study participants were assigned to this subtype.
- Mixed ASD with developmental delay: Individuals in this group will often reach developmental milestones later than children without ASD. They typically do not present with symptoms of conditions such as anxiety, depression or disruptive behaviors. Approximately 19% of the study participants were assigned to this subtype.
- Moderate challenges: Individuals may show core autism traits, but less than individuals in the other groups. They typically reach developmental milestones at a similar pace to people without ASD and do not experience other psychiatric conditions. Approximately 34% of the study participants were assigned to this subtype.
- Broadly affected: Individuals in this category experience a variety of challenges, including social and communication issues, developmental delays, repetitive behaviors and psychiatric conditions. Approximately 10% of the study participants were assigned to this subtype.
The data point to specific mechanisms underpinning similar clinical presentations of ASD. For instance, the highest number of de novo mutations was identified in the broadly affected group. The mixed ASD with developmental delay group was more likely to possess inherited genetic variants.
Children in the social and behavioral challenges subtype, where a later ASD diagnosis is common, possessed mutations in genes that are often activated later in life, possibly explaining why some children present with ASD symptoms as they get older.
De novo mutations vs inherited genetic variants
A de novo mutation is a genetic alteration that presents for the first time in one individual, rather than being inherited from their parents.
An inherited genetic variant, in contrast, is a genetic variant that is inherited from an individual’s parents.
“What we’re seeing is not just one biological story of autism, but multiple distinct narratives,” said Natalie Sauerwald, associate research scientist at the Flatiron Institute and co-lead author.
“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. We couldn’t see the full picture, the genetic patterns, until we first separated individuals into subtypes,” she continued.
What could these ASD subtypes mean for families?
Though this study presents four subtypes of ASD, the research group emphasizes that there could be more. “We now have a data-driven framework that shows there are at least four – and that they are meaningful in both the clinic and the genome,” said Littman.
Tailoring diagnosis to specific subtypes may significantly improve ASD detection and guide families in understanding future outcomes.
“It could tell families, when their children with autism are still young, something more about what symptoms they might – or might not – experience, what to look out for throughout a lifespan, which treatments to pursue, and how to plan for their future,” study co-author Jennifer Foss-Feig, a clinical psychologist at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai and vice president and senior scientific officer at the Simons Foundation Autism Research Initiative, concluded.
Reference: Litman A, Sauerwald N, Green Snyder L, et al. Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs. Nat Gen. 2025. doi: 10.1038/s41588-025-02224-z
