By leveraging a person-centered computational approach too phenotypic data from more than 5000 children with autism spectrum disorder (ASD), researchers have identified four biologically and clinically distinct subtypes of autism and their underlying genetic signals.
These four subtypes are: Social and Behavioral Challenges, Mixed ASD with Developmental Delay, Moderate Challenges, and Broadly Affected.
“It’s vital for families to have groups where they can really understand how they belong and what kind of prognosis their child might have,” a study investigator said. “Ther’s very different clinical presentations depending on these subtypes and if you know which subtype a child belongs to – it’s not yet full precision medicine – but you’d be able to make nontrivial predictions about the prognosis for these children.”
the study was published on July 9 in Nature Genetics.
Unique Research approach
Patients with ASD exhibit overlapping social and neurocognitive impairment and considerable genetic and phenotypic heterogeneity. However, a coherent mapping of genetic variation to phenotypes is lacking, despite the rising number of ASD diagnoses and hundreds of ASD-associated genes identified in recent years.
Prior studies have either focused purely on clinical or genetic features in relatively small groups or tried to combine them in a trait-centered approach looking for genetic links to single traits.
What’s different here is the scale and use of a person-centered approach to identify 239 item-level and composite phenotype features in 5392 individuals. Each feature was then assigned to one of seven phenotype categories defined in the literature (limited social communication, restricted and/or repetitive behavior, attention deficit, disruptive behavior, anxiety and/or mood symptoms, developmental delay, and self-injury) and a general finite mixture model was used to identify and validate the four latent classes.”As far as we certainly know, this is the first work that was able to combine this person-centered phenotype-first approach with some really surprising genetic findings that align extremely well with these phenotypic results.”
Clear Clinical Potential
The four subtypes differ not only in severity of autism symptoms but also in the degree to which co-occurring cognitive, behavioral, and psychiatric concerns factor into their presentation, the researchers noted.
Individuals in the Social and Behavioral Challenges class had greater difficulties across core autism categories of social communication and restricted and/or repetitive behaviors than other autistic children. Developmental delays were not reported but scores were higher for disruptive behavior, attention deficit, and anxiety. This was the largest group with 1976 persons, accounting for 37% of study participants.
The Mixed ASD with Developmental Delays class was highly enriched in language delays, intellectual disability, and motor disorders compared with nonautistic siblings and children in other classes. The 1102 individuals in this group had some features enriched and some depleted with respect to repetitive behaviors and social challenges but had lower levels of attention-deficit/hyperactivity disorder (ADHD), anxiety, and depression. About 19% of participants fell into this class.Individuals in the Moderate Challenges class showed core autism-related behaviors but less strongly than those in other groups and usually reached developmental milestones at the same pace as nonautistic siblings. this group included 1860 persons or about 34% of participants.
The Broadly Affected class showed significant