Al-Beltagi M. Enigma of autism regression mechanistic pathways, clinical phenotypes, and early intervention implications. World J Clin Pediatr 2026; 15(2): 118495 [DOI: 10.5409/wjcp.v15.i2.118495]
Corresponding Author of This Article
Mohammed Al-Beltagi, MD, PhD, Professor, Department of Pediatrics, Faculty of Medicine, Tanta University, 1 Hassan Radwan Street, Tanta 31511, Algharbia, Egypt. mbelrem@hotmail.com
Research Domain of This Article
Pediatrics
Article-Type of This Article
Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jun 9, 2026 (publication date) through May 16, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Pediatrics
ISSN
2219-2808
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Al-Beltagi M. Enigma of autism regression mechanistic pathways, clinical phenotypes, and early intervention implications. World J Clin Pediatr 2026; 15(2): 118495 [DOI: 10.5409/wjcp.v15.i2.118495]
World J Clin Pediatr. Jun 9, 2026; 15(2): 118495 Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.118495
Enigma of autism regression mechanistic pathways, clinical phenotypes, and early intervention implications
Mohammed Al-Beltagi
Mohammed Al-Beltagi, Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
Mohammed Al-Beltagi, Department of Pediatric, University Hospital, Arabian Gulf University, Manama 26671, Manama, Bahrain
Author contributions: Al-Beltagi M was responsible for conceptualizing and designing the review, conducting the extensive literature search and data acquisition, analyzing and interpreting the integrated biological models, and drafting the manuscript; Al-Beltagi M critically revised the work for intellectual content, designed the clinical algorithms and tables, and provided final approval for the version to be published.
Conflict-of-interest statement: Professor Mohammed Al-Beltagi, declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. No external funding was received for the preparation of this review, and the author has no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.
Corresponding author: Mohammed Al-Beltagi, MD, PhD, Professor, Department of Pediatrics, Faculty of Medicine, Tanta University, 1 Hassan Radwan Street, Tanta 31511, Algharbia, Egypt. mbelrem@hotmail.com
Received: January 4, 2026 Revised: January 23, 2026 Accepted: February 26, 2026 Published online: June 9, 2026 Processing time: 129 Days and 23.6 Hours
Core Tip
Core Tip: Autism regression, affecting up to one-third of children with autism spectrum disorder, represents a sudden loss of previously acquired social, communicative, or language skills, typically between 12 months and 30 months. This review synthesizes recent evidence, framing regression as a biologically grounded neurodevelopmental event driven by dysregulation of synaptic pruning, excitatory-inhibitory imbalance, neuroinflammation, and disturbances of the mitochondrial or gut-brain axis. Early identification of subtle pre-regression signs, combined with a two-track clinical approach—rapid medical evaluation and immediate initiation of evidence-based therapies such as naturalistic developmental behavioral interventions and parent-mediated interventions—can harness neuroplasticity, promote functional skill recovery, and optimize long-term developmental outcomes.
