What are the causes of autism?

Causes of Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is predominantly caused by genetic factors, with heritability estimated at approximately 90%, as evidenced by twin studies showing 70% concordance in monozygotic twins versus only 3% in dizygotic twins. 1

Genetic Factors

• Multiple lines of epidemiologic evidence support genetics as the primary etiology of ASD:

  • Twin studies demonstrate the strong genetic component (70% concordance in identical twins vs. 3% in fraternal twins) 1
  • Sibling recurrence risk is 4-19%, significantly higher than general population prevalence 1
  • Specific recurrence risks vary: 7% if first affected child is female, 4% if male, and 25-35% if two or more children are already affected 1

• Genetic inheritance patterns are complex:

  • Multifactorial inheritance rather than simple Mendelian patterns 1
  • Marked genetic heterogeneity with linkages across multiple chromosomes 1
  • Most consistently reported linkages involve chromosomal locations 15q11-13, 7q22-31, 13q, 17q11, 2q, and 16p 1

Sex Differences

• Males are affected 3-4 times more frequently than females 1
• X chromosome genes account for only a small portion of the overall genetic contribution 1
• Male-to-male transmission in multiple families rules out X-linkage as the predominant inheritance mode 2

Environmental and Other Risk Factors

While genetics play the primary role, several environmental factors may contribute to ASD risk:

• Advanced maternal or paternal age 1
• Closer spacing of pregnancies 1
• Extremely premature birth (less than 26 weeks gestational age) 1
• Prenatal exposure to environmental chemicals, including:
  • Air pollutants
  • Pesticides
  • Various chemicals in household products 1

Neurobiological Findings

Several neurobiological abnormalities have been associated with ASD:

• Aberrations in white matter tract development 1
• Elevated peripheral serotonin levels 1
• Possible imbalance of excitation and inhibition in neural systems 1
• Abnormal brain growth patterns 1
• Differences in brain function during social and affective judgment tasks (shown by fMRI) 1
• Overall brain size increase (shown by structural MRI) 1

Common Comorbidities

Individuals with ASD frequently have comorbid conditions:

• ADHD, GI disorders, and disrupted sleep (affecting more than half of individuals with ASD) 1
• Epilepsy (occurs in 5-46% of children with ASD) 1
• Motor impairments (delayed milestones, apraxia, hypotonia, malcoordination) 1
• Sleep disturbances (prevalent in 53-78% of individuals) 1
• Anxiety disorders 1

Important Caveats and Considerations

• The rise in reported prevalence (currently approximately 1 in 36-59 children) is likely due to:

  • Better knowledge of the disorder
  • Broader diagnostic criteria
  • Improved awareness
  • Higher acceptance of the diagnosis 1

• Currently diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects (e.g., tuberous sclerosis complex, fragile X syndrome) account for less than 10% of ASD cases 2

• The wide phenotypic variability of ASD likely reflects:

  • Interaction of multiple genes within an individual's genome
  • Existence of distinct genes and gene combinations among affected individuals 2

• Genetic counseling is important for families regarding recurrence risk, which is significantly higher than general population prevalence 1