Autism Spectrum Disorder Diagnosis
Autism spectrum disorder should be diagnosed through a comprehensive multidisciplinary assessment using standardized tools like the Autism Diagnostic Observation Schedule (ADOS), with routine screening at 18 and 24 months using the Modified Checklist for Autism in Toddlers (M-CHAT), followed by a tiered genetic evaluation that identifies an underlying etiology in 30-40% of cases. 1, 2
Initial Screening and Diagnostic Confirmation
Screen all children at 18 and 24 months using validated tools like the M-CHAT during routine well-child visits, even without specific concerns. 1, 3 Earlier screening is warranted when developmental concerns exist, using tools such as the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP) or First Year Inventory (FYI). 1
Key early signs to identify between 12-24 months include:
- Reduced eye contact and social smiling 1
- No response to name when called 3
- Limited nonverbal behaviors to initiate shared experiences 1
- No or limited use of gestures in communication 3
- Lack of imaginative or pretend play 3, 1
- Atypical object use and repetitive behaviors 1
Diagnostic confirmation must be performed by trained professionals using objective criteria with standardized measures including the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2, sensitivity 91%, specificity 76%) and Autism Diagnostic Interview (sensitivity 80%, specificity 72%). 3, 1 The evaluation should include direct observation of the child's behavior, structured parent interviews, and cognitive/language assessment. 1
Essential Medical Workup
Every child with suspected ASD must have a formal audiogram to rule out hearing loss that could mimic ASD symptoms before proceeding with further evaluation. 2, 1
Establish a primary care medical home for every individual with ASD to coordinate diagnostic testing and ongoing care. 2
Tiered Genetic Evaluation
A genetic consultation should be offered to all persons/families with ASD, as a thorough clinical genetics evaluation identifies an underlying etiology in 30-40% of individuals. 2
First Tier (Highest Yield)
Evaluation by a clinical geneticist/dysmorphologist remains high-yield and low-cost for identifying syndromic versus isolated ASD through examination for dysmorphic features and family history analysis. 2
Order the following genetic tests with expected diagnostic yields:
- Chromosomal microarray (CMA): 10% yield 2
- Fragile X DNA testing: 1-5% yield overall, up to 5% in appropriate populations 2
- High-resolution karyotype: 3% yield 2
Second Tier (Targeted Testing)
MECP2 gene testing in females: 4% yield in females with ASD 2
PTEN gene testing: 5% yield in patients with head circumference >2.5 standard deviations above the mean 2
Additional identifiable causes including brain anomalies, metabolic disorders, and other genetic syndromes account for approximately 10% of cases. 2
Treatment Approach
Intensive behavioral interventions are first-line therapy, particularly for children 5 years or younger, focusing on improving language, play, and social communication skills with small to medium effect sizes. 1, 3 The Early Start Denver Model is specifically beneficial for this age group. 3
Pharmacotherapy is reserved for co-occurring conditions and specific symptoms, not core ASD features. 1, 3
For irritability and aggression: Risperidone (starting at 0.25-0.5 mg/day depending on weight, titrated to clinical response with mean doses of 1.4-1.9 mg/day) or aripiprazole demonstrate large effect sizes (standardized mean difference 1.1) compared to placebo. 4, 3 The FDA-approved dose range for risperidone in autistic disorder is 0.5-3.5 mg/day on a weight-adjusted basis. 4
For co-occurring ADHD: Psychostimulants show moderate effect sizes (standardized mean difference 0.6) compared to placebo. 3
Monitor for medication adverse effects including changes in appetite, weight, and sleep. 3
Genetic Counseling and Follow-up
Provide genetic counseling to all families regardless of whether an etiology is identified. 2, 1
For families without identified etiology, use empiric recurrence risk data:
- Full sibling recurrence risk: 3-10% (higher in recent studies) 2
- Modified by sex: 7% if affected child is female, 4% if affected child is male 2
- With two or more affected children: at least 30% recurrence risk 2
Schedule periodic reevaluations for patients without a definitive etiology, as diagnostic technology and understanding continue to evolve. 2
Critical Pitfalls to Avoid
Do not delay diagnosis due to misconceptions about presentation, particularly in adults or atypical cases. 5 Most children are not diagnosed until 4-5 years of age despite evidence that definitive diagnosis is possible by 2 years. 6
Do not focus solely on core ASD symptoms while missing co-occurring conditions. Individuals with ASD have significantly higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with intellectual disability vs 0.8%) compared to the general population. 3
Do not order extensive genetic testing without clinical geneticist evaluation first, as the stepwise approach with higher-tier tests having greater diagnostic yield is more cost-effective and better tolerated by families. 2
Do not fail to provide recurrence risk information to families, as this is essential for family planning and understanding. 2, 1