Description

• Group of neurodevelopmental disorders of early childhood characterized by (i) persistent deficits in social communication and interaction and (ii) restricted, repetitive patterns of behavior, interests, or activities
• Diagnostic and Statistical Manual of Mental Disorders, 5th edition, text revision: umbrella term autism spectrum disorder (ASD), which encompasses a group of pervasive developmental disorders with designations for varying severities and associated symptoms
• ASD combines former diagnoses, including autistic disorder, childhood disintegrative disorder, Asperger disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), early infantile autism, childhood autism, Kanner autism, high-functioning autism, and atypical autism, many of which are still used by ICD-10 coding.
• Although symptoms must be present in early development period, they may not be apparent until social demands exceed capacity.
• Symptoms must cause functional impairment. Severity levels:
  • Level 1: requiring support—noticeable impairment
  • Level 2: requiring substantial support—marked deficits
  • Level 3: requiring very substantial support—severe impairments interfering with functionality
• Specifiers for associated symptoms include with catatonia; intellectual impairment; language impairment; known medical or genetic condition; and neurodevelopmental, mental, or behavioral disorders.
• Important to distinguish ASD from symptoms that could be better explained by intellectual disability or global developmental delay

Epidemiology

Onset in early childhood; predominant sex: male > female (approximately 4:1 ratio)

Pediatric Considerations
Symptom onset can often be seen in children <3 years of age but may not become apparent until social demands exceed capacity.

Prevalence

• Centers for Disease Control and Prevention (CDC) in 2018: estimated prevalence of 1 in every 44 children between ages 3 and 17 years carried diagnosis of ASD
• Increase noted since 2000 when the CDC reported prevalence to be 1 in 150, likely due to changes in definition and awareness.
• In 2018, there was no difference in prevalence of non-Hispanic white children diagnosed with ASD compared to non-Hispanic black children. However, the number of Hispanics diagnosed with ASD is lower.

Etiology and Pathophysiology

• No single cause has been identified.
• Consensus: A genetic abnormality leads to altered neurologic development.
• Epidemiologic evidence does not support association between immunizations and ASD.

Genetics

• Genetic concordance: A 2009 Swedish population-based cohort study of 2 million subjects showed a cumulative risk of 59% for monozygotic twins.
• The American College of Medical Genetics and Genomics practice guidelines list the risk of siblings of children diagnosed with ASD without an identifiable cause to be 7% if the affected child is female, 4% if the affected child is male, and >30% if there are two or more affected children.

Risk Factors

• Male sex, advanced paternal age, family history, very low birth weight
• Perinatal insults including toxic exposures, teratogens, prenatal infections, use of selective serotonin reuptake inhibitors (SSRI) or valproate during pregnancy

General Prevention

• Screening for early intervention is associated with improved prognosis, yet median age of diagnosis in the United States is >4 years.
• Routine screening for ASD with a validated tool is recommended at 18- and 24-month well-child visits to assist with early detection.
• Screening is indicated after 24 months if parents or clinician have concerns about ASD as less severe presentations may pass earlier routine screening.
• Children with false positives for ASD frequently have some form of developmental disorder and benefit from early intervention.
• Screening difficult due to variability of signs and symptoms of ASD, and lack of unanimous consensus of social developmental milestones, thus leading to delayed diagnosis.

Commonly Associated Conditions

• Intellectual disability (seizure in severe cases)
• Attention deficit hyperactivity disorder (ADHD), anxiety, depression, or obsessive behavior
• Motor impairments including hypotonia, apraxia, toe walking, or gross motor delays
• Phenylketonuria (PKU), tuberous sclerosis, fragile X syndrome, Angelman syndrome, Rett syndrome, CHARGE syndrome, Joubert syndrome, Smith-Lemli-Opitz syndrome, Timothy syndrome, and fetal alcohol syndrome (rare)
• Sleep issues: insomnia, circadian rhythm sleep–wake disorder, sleep-related movement disorder
• Change in bowel habits, abdominal pain