What diagnostic evaluation and assessments are necessary to determine the type of Autism Spectrum Disorder (ASD) someone has?

Determining Autism Spectrum Disorder Type and Etiology

Modern diagnostic frameworks no longer classify autism into distinct "types"—DSM-5 consolidated all previous subtypes (Asperger's, PDD-NOS, autistic disorder) into a single diagnosis of Autism Spectrum Disorder, so the focus is now on identifying the underlying etiology and characterizing severity across two core domains: social communication deficits and restricted/repetitive behaviors. 1, 2

Initial Diagnostic Confirmation

Before pursuing any etiologic workup, confirm the ASD diagnosis itself through:

• Evaluation by a trained professional using standardized diagnostic tools—specifically the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2, sensitivity 91%, specificity 76%) and Autism Diagnostic Interview-Revised (ADI-R, sensitivity 80%, specificity 72%) 3, 2
• Formal audiogram to rule out hearing loss that could mimic ASD symptoms—this is mandatory before proceeding, as hearing impairment can present with similar social-communication difficulties 1, 3, 2
• Cognitive and adaptive skills testing to establish baseline developmental level and frame social difficulties relative to overall functioning 1, 2

Identifying the Underlying Etiology: Tiered Genetic Evaluation

A clinical genetics evaluation identifies an underlying cause in 30-40% of individuals with ASD, which directly impacts medical management, family counseling, and recurrence risk estimation. 3, 2

Pre-Evaluation Requirements

• Verify newborn screening results 1
• Obtain EEG only if clinical suspicion of seizures exists 1
• Consider Landau-Kleffner syndrome evaluation (EEG) when marked aphasia develops 2

First-Tier Testing (Order Initially for All)

• Physical examination by clinical geneticist/dysmorphologist focusing on dysmorphic features—this remains high-yield and low-cost for distinguishing syndromic from isolated ASD 1, 2
• Woods lamp examination for tuberous sclerosis signs 1, 2
• Chromosomal microarray (CMA): 10% diagnostic yield—now standard of care as first-line genetic test 1, 3, 2
• Fragile X DNA testing: 1-5% yield 3, 2
• High-resolution karyotype: 3% yield (if not already performed) 1, 3

Metabolic Screening (Only If Clinical Indicators Present)

Order these only when specific clinical features warrant:

• Urine mucopolysaccharides and organic acids 1
• Serum lactate, amino acids, ammonia, and acyl-carnitine profile 1
• Rubella titers if clinical indicators present 1

Second-Tier Testing (Based on Specific Clinical Features)

• MECP2 gene testing in females only: 4% yield 1, 3, 2
• PTEN gene testing if head circumference >2.5 standard deviations above mean: 5% yield 1, 3, 2
• Fibroblast karyotype if leukocyte karyotype normal but clonal pigmentary abnormalities noted 1

Third-Tier Testing (For Specific Clinical Scenarios)

• Brain MRI (not routine—only when neurologic features warrant) 1, 2
• Serum and urine uric acid with follow-up enzyme testing if abnormal 1

Characterizing ASD Severity and Co-occurring Conditions

Beyond identifying etiology, characterize the individual's presentation across these dimensions:

Intellectual Disability Assessment

• 39.6% of children with ASD have co-occurring intellectual disability, with higher rates among Black (52.8%), AI/AN (50.0%), and A/PI (43.9%) children compared to White (32.7%) and multiracial (31.2%) children 4
• Cognitive testing reveals considerable scatter with possible splinter skills or savant abilities in specific domains 2

Psychiatric Comorbidity Screening

• Approximately 75% of children with ASD have comorbid psychiatric conditions including ADHD, anxiety disorders, mood disorders, and Tourette syndrome 3, 5
• Screen systematically for these conditions as they require separate management 1, 5

Critical Pitfalls to Avoid

• Do not order extensive genetic testing without clinical geneticist evaluation first—the stepwise approach is more cost-effective and better tolerated by families than shotgun testing 3, 2
• Do not delay diagnosis waiting for genetic results—the ASD diagnosis itself is clinical and should not be held up by etiologic workup 1
• Do not fail to provide recurrence risk counseling even when no etiology is identified: full sibling recurrence risk is 3-10% (7% if affected child is female, 4% if male), rising to at least 30% with two or more affected children 3, 2
• Do not assume lower IQ predicts positive genetic findings—recent data shows IQ is not a strong predictor of chromosomal abnormalities 1

Ongoing Management

• Schedule periodic reevaluations for patients without definitive etiology, as diagnostic technology continues to evolve 3, 2
• Establish a primary care medical home to coordinate ongoing care 1, 2
• Refer for intensive behavioral interventions (first-line therapy, particularly for children ≤5 years) focusing on language, play, and social communication 3, 2
• Reserve pharmacotherapy for co-occurring conditions and specific symptoms, not core ASD features 3, 2