Four Hidden Types of Autism Revealed, Each Telling a Unique Genetic Story

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Revolutionary study from Princeton and the Simons Foundation uncovers distinct autism subtypes with different developmental paths, symptoms, and genetic mechanisms

By Staff Writer | Open Chronicle Science

July 24, 2025 — Princeton, NJ – A groundbreaking study from Princeton University and the Simons Foundation has revealed four distinct subtypes of autism, each characterized by unique traits, developmental timelines, and underlying genetic signatures. Drawing from the clinical and genetic data of over 5,000 children, this research provides a new framework that could transform autism diagnosis, treatment, and understanding.

Published in Nature Genetics, the study breaks away from traditional methods by taking a “person-centered” approach. Rather than linking individual genes to single symptoms, researchers analyzed over 230 clinical traits per participant, including social behaviors, repetitive actions, and developmental milestones. This method allowed them to uncover biologically and clinically meaningful autism subtypes, providing a clearer window into the genetic and neurodevelopmental complexity of autism spectrum disorder (ASD).

“We’re not just telling one story about autism anymore,” said lead researcher Dr. Olga Troyanskaya, director of Princeton Precision Health. “We’re uncovering multiple, distinct biological narratives, each with different timelines and genetic mechanisms.”

The Four Autism Subtypes

1. Social and Behavioral Challenges (37%)
   Children in this group display the core features of autism — difficulties in social interaction and repetitive behaviors, but typically achieve developmental milestones like walking and speaking at expected ages. They are more likely to have co-occurring conditions such as ADHD, anxiety, or depression.

2. Mixed ASD with Developmental Delay (19%)
   These children experience delays in motor and verbal development but are less likely to exhibit psychiatric symptoms. Their autism symptoms vary in severity, and their genetic patterns include more inherited mutations, suggesting a different biological origin from other subtypes.

3. Moderate Challenges (34%)
   This group shows milder symptoms overall and generally follows typical developmental timelines. They are less likely to be diagnosed with co-occurring psychiatric conditions, representing a relatively moderate presentation of autism.

4. Broadly Affected (10%)
   The smallest but most complex group, these children face wide-ranging challenges including severe developmental delays, communication issues, and psychiatric conditions. They also show the highest levels of damaging de novo (non-inherited) genetic mutations.

A Deeper Genetic Divide

Each subtype is underpinned by a distinct genetic architecture. Children in the Broadly Affected group, for example, showed a high incidence of spontaneous genetic mutations, while those in the Mixed ASD with Developmental Delay group more often carried rare, inherited variants. This discovery not only differentiates superficially similar clinical presentations but also identifies new targets for future research and therapy.

“These insights reveal that what might appear similar on the surface can be biologically very different underneath,” said Aviya Litman, a PhD student at Princeton and co-lead author. “This has enormous implications for how we screen, diagnose, and ultimately treat autism.”

Timing Is Everything

One of the study’s most intriguing findings is the timing of when autism-related genetic disruptions exert their effects. In the Social and Behavioral Challenges group, the relevant genes activate later in childhood, correlating with the group’s later diagnoses. This challenges the traditional view that autism is exclusively rooted in prenatal brain development.

Toward Precision Medicine for Autism

This study represents a shift toward personalized care for autism. By identifying subtypes based on both behavior and biology, clinicians could tailor interventions and monitor children more precisely, rather than applying a one-size-fits-all approach.

“This opens the path to true precision medicine in autism,” said Dr. Jennifer Foss-Feig of the Icahn School of Medicine and the Simons Foundation. “Families could one day receive much more specific information about their child’s likely developmental path, needed supports and effective treatments.”

Broader Implications

Beyond autism, this approach could serve as a blueprint for understanding other complex, heterogeneous conditions. By separating different clinical and genetic profiles within a broad diagnosis, scientists can more effectively uncover root causes and therapeutic opportunities.

“Trying to find a single explanation for autism was like solving multiple puzzles with pieces from different boxes,” said co-lead author Natalie Sauerwald. “This study finally sorts those pieces into the correct puzzles.”

As research progresses, more subtypes may be revealed. For now, this study provides a robust, data-driven foundation to understand the diversity of autism in a clearer, more actionable way.

Published in: Nature Genetics, July 9, 2025
Title of the paper: Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs

Institutions involved:

• Princeton University

• Simons Foundation

• Flatiron Institute

• Icahn School of Medicine at Mount Sinai

• Ben Gurion University of the Negev

Supported by:
U.S. National Institutes of Health, Simons Foundation