Autism Spectrum Disorder in the Genomic Era: A Comprehensive Review of Etiology, Precision Diagnostics, Clinical Outcomes, and Emerging Gene-Editing Therapies.

Authors

Nating Xiong, Zhikang Yu

Published in

Neuropsychiatric disease and treatment. Volume 22. Pages 585060. Epub Feb 07, 2026.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous, lifelong neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Over recent decades, diagnostic expansion and methodological advances have led to increased prevalence estimates and a deeper appreciation of phenotypic, etiological, and outcome heterogeneity. This review synthesizes evidence from 2015-2024 across epidemiology, clinical diagnosis, neurobiology, genetics, environmental risk factors, mortality, and treatment. We summarize robust genetic contributions, including polygenic risk from common variants and high-impact rare or de novo mutations converging on synaptic function, chromatin regulation, and neurodevelopmental pathways. Prenatal and perinatal environmental exposures such as maternal immune activation, air pollution, and selected teratogens interact with genetic susceptibility through inflammatory, oxidative, and epigenetic mechanisms to influence ASD risk. Neuroimaging and multimodal studies reveal altered cortical developmental trajectories and atypical large-scale network connectivity associated with core symptoms and common comorbidities. Mortality studies demonstrate increased all-cause and cause-specific mortality, particularly related to epilepsy, medical comorbidities, and injury, with highest risk observed in individuals with intellectual disability. Current treatments remain primarily symptomatic, with early, intensive, and individualized behavioral interventions providing the greatest functional benefit, while pharmacotherapy targets associated behavioral challenges. Emerging genomic technologies, including CRISPR-based approaches, offer powerful experimental models and potential precision therapies for selected monogenic or high-impact copy number variant-associated ASD, although substantial safety, delivery, and ethical challenges remain. We conclude by highlighting priorities for integrative longitudinal studies, mechanistic links between molecular and circuit-level dysfunction, and responsible translational pathways toward precision therapeutics.

PMID:
41908337
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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