Investigating Early Behavioral and Genetic Markers for Improved Diagnosis and Intervention Strategies in Children With Autism Spectrum Disorder

Abstract

Background: Autism Spectrum Disorder (ASD) is a prevalent neurodevelopmental condition, and early diagnosis is critical for accessing interventions during a period of high neuroplasticity. Current diagnosis relies on behavioral identification, often delayed until later childhood. While early behavioral signs and genetic factors are increasingly studied, a comprehensive synthesis of their interplay as dual markers for early risk stratification is needed. Objective: This systematic review aimed to identify and synthesize evidence on key early behavioral and genetic markers that can aid in the improved and earlier diagnosis of ASD, and to explore their potential integration for informing intervention strategies. Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed for studies published between 2019 and 2024. Inclusion criteria encompassed observational studies of children under six years investigating early behavioral and/or genetic markers related to ASD diagnosis. Study selection, data extraction, and risk-of-bias assessment using the Newcastle-Ottawa Scale were performed by two independent reviewers. A narrative synthesis was undertaken due to methodological heterogeneity. Results: Eight studies were included (n>15,000 participants). The evidence consistently identified diminished social attention (e.g., reduced eye contact), motor delays, and atypical patterns in nonverbal communication as robust early behavioral predictors. Genetically, a significant burden of rare protein-truncating variants and higher polygenic risk scores were associated with ASD. One pivotal study demonstrated that a high polygenic risk was correlated with altered visual processing in the infant brain, suggesting a direct gene-brain-behavior pathway. The predictive model integrating parent-reported social concerns showed high diagnostic accuracy (AUC=0.82). Conclusion: This review confirms that a constellation of behavioral and genetic markers is detectable in infancy and early childhood, preceding a formal ASD diagnosis. The convergence of these domains offers a powerful framework for developing multivariable, pre-symptomatic risk models. Future research should focus on validating integrated models that combine genetic liability with specific behavioral phenotypes to facilitate the earliest possible identification and personalized intervention