Autism

With several family members exhibiting some autistic traits, and with a history of teaching autists in my working life, I read numerous articles about autism. Here is one that I found interesting that I would like to share.

Researchers have discovered four autism subtypes that are both clinically and biologically distinct. This research offers a better understanding of the genetic foundations of autism and could support more personalized approaches to diagnosis and care.

Data from more than 5 000 children was applied a computational model to group individuals by shared patterns of traits. Researchers adopted a person-centered strategy that evaluated more than 230 traits per participant, including social behavior, repetitive actions, and developmental progress.

This method led to the identification of meaningful autism subtypes, each tied to unique genetic markers and developmental patterns.

Understanding the genetics of autism is essential for revealing the biological mechanisms that contribute to the condition, enabling earlier and more accurate diagnosis, and guiding personalized care. The study identifies four distinct autism subtypes: 1. Social and Behavioral Challenges, 2. Mixed ASD with Developmental Delay, 3. Moderate Challenges, and 4. Broadly Affected. Each group displays unique profiles in terms of development, medical conditions, behavioral traits, psychiatric symptoms, and genetic variation.

Subtype 1: The Social and Behavioral Challenges group is characterized by core autism features, such as difficulties with social interaction and repetitive behaviors, but these individuals typically meet developmental milestones at a similar rate as their neurotypical peers. However, they often experience additional conditions such as: a. ADHD, b. anxiety, c. depression, or obsessive-compulsive behaviour. This is one of the more common subtypes, representing about 37% of the study population.

Subtype 2: The Mixed Autism Spectrum Disorder (ASD) with Developmental Delay group is marked by delayed developmental milestones like walking and talking. Most individuals in this category do not exhibit anxiety, depression, or disruptive behavior. Mixed reflects the variation in social difficulties and repetitive behaviors within the group. Approximately 19% of participants belong to this category.

Subtype 3: The Moderate Challenges group display autism-related behaviors, but these traits tend to be less pronounced than in the other subtypes. Their developmental milestones generally align with typical patterns, and they rarely show psychiatric comorbidities = the simultaneous presence of two or more medical conditions in a patient. This group makes up roughly 34% of participants.

Subtype 4: The Broadly Affected group have the most severe and wide-ranging symptoms, including significant developmental delays, difficulties with social communication, repetitive behaviors, and coexisting psychiatric conditions, such as anxiety, depression, and mood instability. This is the smallest group, comprising about 10% of participants.

The findings are powerful because the classes represent different clinical outcomes, and connect to distinct underlying biology.

For decades, autism researchers and clinicians have been seeking robust definitions of autism subtypes to aid in diagnosis and care. Autism is known to be highly heritable, with many implicated genes.

Genetic testing is part of the standard of care for people diagnosed with autism, but this testing reveals variants that explain the autism of only about 20% of patients. In contrast, this study identifies autism subtypes that are linked to distinct types of genetic mutations and affected biological pathways.

People in the Broadly Affected group exhibit the highest rate of damaging de novo mutations = genetic changes that arise spontaneously and are not passed down from either parent. Those in the Mixed ASD with Developmental Delay group were more likely to possess rare inherited genetic variants. Although both subtypes share key features, these genetic distinctions point to separate biological mechanisms underlying what may appear to be similar clinical traits.

“These findings point to specific hypotheses linking various pathways to different presentations of autism,” said Litman, referring to differences in biology between children with different autism subtypes.

Researchers identified divergent biological processes affected in each subtype. Autism is not just one biological story, but multiple distinct narratives. Past genetic studies often fell short. It was like someone trying to solve a jigsaw puzzle without realizing that researchers were looking at multiple different puzzles mixed together. They couldn’t see the full picture, until individuals were separated into subtypes.

Autism subtypes differ in the timing of genetic disruptions’ effects on brain development. Genes switch on and off at specific times, guiding different stages of development. Previously much of the genetic impact of autism was thought to occur before birth. However, in the Social and Behavioral Challenges subtype, which typically has substantial social and psychiatric challenges, no developmental delays, and a later diagnosis, mutations were found in genes that become active later in childhood. This suggests that, for these children, the biological mechanisms of autism may emerge after birth, aligning with their later clinical presentation.

“It’s a whole new paradigm, to provide these groups as a starting point for investigating the genetics of autism,” said Theesfeld. Instead of searching for a biological explanation that encompasses all individuals with autism, researchers can now investigate the distinct genetic and biological processes driving each subtype.

This shift could reshape both autism research and clinical care — helping clinicians anticipate different trajectories in diagnosis, development, and treatment. “The ability to define biologically meaningful autism subtypes is foundational to realizing the vision of precision medicine for neurodevelopmental conditions,” said Sauerwald.

While the current work defines four subtypes, this doesn’t mean there are only four classes. It means 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.

For families navigating autism, knowing which subtype of autism their child has can offer new clarity, targeted care, support, and community. 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 over the course of a lifespan, which treatments to pursue, and how to plan for their future.

Reference: “Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs” by Aviya Litman, Natalie Sauerwald, LeeAnne Green Snyder, Jennifer Foss-Feig, Christopher Y. Park, Yun Hao, Ilan Dinstein, Chandra L. Theesfeld and Olga G. Troyanskaya, 9 July 2025, Nature Genetics. DOI: 10.1038/s41588-025-02224-z