What is the most common cause (MCC) of Autism Spectrum Disorder (ASD)?

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From the Guidelines

The most common cause (MCC) of autism is genetic factors, with hundreds of genes identified that, when altered, can increase the risk of developing autism, as supported by the most recent and highest quality study 1. Autism spectrum disorder (ASD) is primarily caused by a combination of genetic mutations and variations that affect brain development. These genetic factors can be inherited from parents or occur as new mutations. Environmental factors may also play a role, particularly during pregnancy, but they typically interact with genetic predispositions rather than causing autism independently. Twin studies strongly support the genetic basis, showing that if one identical twin has autism, the other has a much higher chance of also having it compared to fraternal twins, as discussed in 1. While specific genes like SHANK3, CHD8, and those related to synaptic function have been implicated, autism is considered a complex polygenic disorder, meaning multiple genes contribute to its development rather than a single gene being responsible in most cases. Early diagnosis and intervention remain crucial for improving outcomes, regardless of the specific genetic causes, as emphasized in 1 and 1. Key points to consider include:

  • Genetic testing, including chromosomal microarray analysis, is warranted and clinically indicated for all suspected cases of ASD, as recommended in 1.
  • The yield of genetic testing in the presence of clinical suspicion is currently in the range of at least one third of cases, highlighting the importance of genetic evaluation in ASD diagnosis, as noted in 1.
  • Unusual features in the child, such as history of regression, dysmorphology, staring spells, or family history, should prompt additional evaluations, including genetic or neurologic consultation, neuroimaging, EEG, and additional laboratory tests, as suggested in 1. Overall, the current evidence suggests that genetic factors play a significant role in the development of autism, and further research is needed to fully understand the complex interplay between genetic and environmental factors, as discussed in 1 and 1.

From the Research

Molecular and Cellular Causes of Autism

  • The exact molecular and cellular causes of autism are not fully understood, but research suggests that genetic and environmental factors play a significant role in the development of autism spectrum disorder (ASD) 2.
  • Genetic processes, environmental events, gene × environment interactions, and developmental factors all contribute to the variability of the autism spectrum 3.
  • The development of neural atypicality reflects an interaction of genetic and environmental risk factors, and changes in neural atypicality, consequent variation in behavior, and environmental response to that behavior may become linked in a positive feedback loop that amplifies deviations from the typical developmental pattern 3.

Environmental Triggers of Autism

  • Environmental factors, such as exposure to certain toxins or infections during pregnancy, may also contribute to the development of autism 2.
  • However, research suggests that environmental factors are unlikely to explain the increase in the prevalence of ASD, and genetic factors play a consistently larger role than environmental factors 4.
  • The existence of an unknown factor that may be common in all autistic cases cannot be ruled out, and large-scale epidemiological research is essential to construct a new theory that can interpret the pathology of autism in a coherent manner 2.

Treatment and Intervention of Autism

  • Early intervention is recognized as key to improving long-term outcomes for individuals with autism, and treatment with risperidone or aripiprazole combined with standard supportive therapies may improve ASD core signs and symptoms in young children 5.
  • Applied behavior analysis (ABA) has strong evidence of effectiveness in helping people with autism achieve goals, and occupational therapists may benefit from incorporating ABA principles into their practice 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Triggers for autism: genetic and environmental factors.

Journal of central nervous system disease, 2012

Research

The development of autism spectrum disorders: variability and causal complexity.

Wiley interdisciplinary reviews. Cognitive science, 2017

Research

Applied Behavior Analysis, Autism, and Occupational Therapy: A Search for Understanding.

The American journal of occupational therapy : official publication of the American Occupational Therapy Association, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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