Cohort study reveals distinct immune and synaptic genetic deletions in children with regressive autism spectrum disorder, indicating a distinct biological subtype.
Key Points
To identify the clinical predictors, phenotypic outcomes, and underlying genetic pathways associated with developmental regression in children with autism spectrum disorder.
Analyzed a cohort of 505 children diagnosed with autism spectrum disorder between 2017 and 2023 in Paris, France, using retrospective and prospective data.
Evaluated developmental trajectories and clinical features using standardized tools (ADI-R, ADOS-2, VABS) alongside classification tree models and principal component analysis.
Conducted chromosomal microarray analysis and gene ontology enrichment to identify distinct copy number variations and molecular pathways.
Developmental regression occurred in 74 children (15%), who initially exhibited more favorable early developmental profiles—such as earlier first words and higher birth parameters—than non-regressive peers.
Post-regression children showed significantly more severe impairments in cognitive, adaptive, and social domains compared to non-regressive peers (p < 0.001), while routine clinical variables failed to predict onset.
Chromosomal microarray analysis identified distinct genetic deletions enriched in immune response, type I interferon, oxidative stress, angiogenesis, and synaptic pathways.