Factors Linked to Autism Spectrum Disorder in Children
Genetic and environmental factors interact in complex ways to contribute to autism spectrum disorder (ASD), with genetics playing the predominant role in most cases. 1
Genetic Factors
Heritability and Family Patterns
- Strong genetic basis with heritability estimated at approximately 90% 1
- Recurrence risk in siblings ranges from 4-19%, much higher than general population prevalence 1
- Specific sibling risks:
- 7% if first affected child is female
- 4% if first affected child is male
- 25-35% if two or more children are already affected 1
- Higher concordance in monozygotic twins (60-92%) compared to dizygotic twins (0-10%) 2
- Multiple genes involved rather than a single gene 1, 3
Genetic Variations
- Most consistently reported genetic linkages include chromosomes 15q11-13, 7q22-31, 13q, 17q11, 2q, and 16p 1
- Rare genetic mutations with large effects are the most robustly identified genetic risks 3
- Specific genetic syndromes associated with ASD:
- Tuberous sclerosis complex (TSC1 and TSC2)
- Fragile X syndrome
- Rett syndrome (MECP2)
- Phelan-McDermid syndrome (SHANK3)
- Angelman syndrome (UBE3A)
- 15q11-q13 duplications
- 16p11.2 deletions 3
Gender-Related Factors
- Male-to-female ratio of approximately 3:1 2
- Female protective effect (FPE) theory suggests females have higher threshold for clinical impairment 3
- Possible protective mechanisms:
- Second X chromosome may be protective
- Y chromosome may be a risk factor 3
- Testosterone levels in early brain development may play a role 3
Environmental Factors
Prenatal and Perinatal Factors
- Advanced maternal or paternal age 3, 1
- Closer spacing of pregnancies 3, 1
- Extremely premature birth (<26 weeks gestational age) 3, 1
- Prenatal exposure to environmental chemicals, including air pollutants and pesticides 1
- Prenatal infections such as rubella and cytomegalovirus (in rare cases) 2
- Exposure to certain medications during pregnancy:
- Valproic acid
- Thalidomide
- Misoprostol 4
Debunked Causes
- No evidence supporting link between vaccines (including MMR) and autism 1, 2
- No established causal relationship between mercury exposure (including thimerosal in vaccines) and ASD 1
Neurobiological Factors
Brain Structure and Function
- Abnormal brain growth patterns 1
- Overall brain size increase in autism 1
- Differences in functional MRI during tasks involving social and affective judgments 1
- Aberrations in white matter tract development 3
Neurochemical Factors
- Elevated peripheral levels of serotonin (one of the most replicated findings) 3
- Possible role of dopamine suggested by response to neuroleptic medications 3
- Possible imbalance of excitation and inhibition in neural systems 3
Common Comorbidities
Neurological Comorbidities
- Epilepsy (occurs in 5-46% of children with ASD) 3
- Motor impairments:
- Delayed motor milestones
- Apraxia
- Hypotonia
- Malcoordination 3
- Sleep disturbances (prevalence 53-78%) 3
Cognitive and Behavioral Comorbidities
- Intellectual disability (variable severity) 3
- Impairments in executive functioning 3
- Weak central coherence (difficulty integrating information) 3
- Deficits in theory-of-mind tasks 3
- Attention disorders 5
- Anxiety disorders 3
Clinical Implications
- Genetic testing, including chromosomal microarray analysis, is clinically indicated for all suspected ASD cases 3, 1
- Medical disorders may affect clinical presentation and response to interventions 3
- Early identification and intervention remain critical for improving outcomes 1
- Heterogeneity in ASD suggests specific subsets of individuals may respond to specific interventions more effectively than others 3
Pitfalls and Caveats
- ASD is heterogeneous in etiology, biology, and clinical presentation 3
- Diagnosis is based on behavioral criteria, not biological markers 5
- Female presentations of ASD may be less obvious and lead to underdiagnosis 3
- Presence of comorbidities may complicate diagnosis and treatment planning 3
- Environmental factors account for a relatively small percentage of cases compared to genetic factors 2