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: 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
  • Level 2: requiring substantial support
  • Level 3: requiring very substantial support
• 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

Predominant age: onset in early childhood; predominant sex: male > female (4:1)

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

Incidence
Estimated 1 in every 110 children in the United States diagnosed per year

Prevalence

• According to the Centers for Disease Control and Prevention (CDC) in 2016, an estimated prevalence of 1 in every 54 children between the ages of 3 and 17 years carried a diagnosis of ASD.
• This has been a steady increase since 2000 when the CDC reported the prevalence to be 1 in 150, likely due to changes in definition and increased awareness.
• In 2016, 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.
• General 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
  • >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 the 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 which also benefits from early intervention.
• Screening can be difficult due to variability of signs and symptoms of ASD along with the 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