What is the best course of action for a child with a complex medical history, who had a first assessment (ax) that did not result in an Autism Spectrum Disorder (ASD) diagnosis, but a second assessment was positive for ASD, and the family is requesting a third assessment?

Autism Reassessment After Discordant Evaluations

Accept the second positive ASD assessment as the definitive diagnosis and proceed with genetic evaluation and treatment planning rather than pursuing a third assessment. When diagnostic evaluations for ASD yield conflicting results, the positive assessment should take precedence because ASD is a clinical diagnosis that can be subtle and easily missed, particularly in younger children or those with milder presentations 1.

Why the Second Assessment Should Stand

The sensitivity of ASD diagnostic tools varies significantly, and false negatives are more common than false positives when evaluations are conducted by trained professionals. The Autism Diagnostic Observation Schedule (ADOS) has a sensitivity of 91% but specificity of only 76%, while the Autism Diagnostic Interview has 80% sensitivity and 72% specificity 1. This means that missing ASD (false negative) is more likely than incorrectly diagnosing it (false positive) when proper diagnostic criteria are used 2.

• Children with ASD often show variable presentation across different evaluations, particularly during the preschool years when symptoms may be emerging or when the child's developmental level affects how symptoms manifest 3, 4.
• The first assessment may have missed subtle signs, especially if the child was younger, had better compensatory skills that day, or if the evaluator had less autism-specific training 5.

Immediate Next Steps After Positive Diagnosis

Rather than seeking a third opinion, focus on confirming the diagnosis was made using standardized measures and then proceed with essential medical workup and genetic evaluation.

Verify Diagnostic Quality

• Confirm the second assessment used objective standardized measures such as ADOS-2, ADI-R, or CARS, not just clinical impression 1, 2.
• Ensure the evaluation was performed by professionals trained in autism assessment using DSM-5 criteria 2, 4.

Essential Medical Workup

• Order a formal audiogram immediately to rule out hearing loss that could mimic or contribute to ASD symptoms - this is mandatory before proceeding further 3, 1.
• Establish a primary care medical home to coordinate ongoing care and testing 3, 1.
• Perform a comprehensive physical examination with attention to dysmorphic features and a Wood's lamp examination for tuberous sclerosis 3, 1.

First-Tier Genetic Testing

Order chromosomal microarray (CMA) and Fragile X testing as first-line genetic evaluation for all children with ASD, as these have the highest diagnostic yields and can identify an underlying etiology in 11-15% of cases combined 3, 1.

• CMA has a 10% diagnostic yield 3.
• Fragile X testing has a 1-5% yield, and should be performed routinely for males 3.
• If the child is female, add MECP2 sequencing (4% yield in females with ASD) 3.
• If head circumference is >2.5 standard deviations above the mean, add PTEN testing (5% yield) 3.

Refer to Clinical Genetics

Arrange evaluation by a clinical geneticist/dysmorphologist, as this remains a high-yield, low-cost component that identifies syndromic versus isolated ASD through examination for dysmorphic features and three-generation family history analysis 3, 1. A thorough clinical genetics evaluation identifies an underlying etiology in 30-40% of individuals with ASD 3.

Addressing Family Concerns About Discordant Assessments

Explain to the family that diagnostic variability is expected in ASD assessment and does not invalidate the positive diagnosis.

• ASD symptoms can fluctuate based on the child's age, developmental stage, environmental context, and stress level during evaluation 3, 4.
• The principle in ASD diagnosis is that if trained evaluators using standardized tools identify ASD, the diagnosis should be accepted rather than seeking repeated evaluations hoping for a different result 1, 2.
• Pursuing additional assessments delays access to early intensive behavioral interventions, which are first-line therapy particularly for children 5 years or younger and have small to medium effect sizes on improving language, play, and social communication skills 1.

When a Third Assessment Might Be Justified

A third evaluation would only be appropriate if:

• The second assessment did not use standardized diagnostic measures (ADOS-2, ADI-R, CARS) 1, 2.
• The evaluator lacked specific training in autism assessment 5.
• There are specific concerns about co-occurring conditions (intellectual disability, language disorder, anxiety) that need clarification for treatment planning 1, 4.

Treatment Initiation Without Delay

Begin intensive behavioral interventions immediately based on the positive diagnosis rather than waiting for a third assessment, as early intervention is critical for optimal outcomes 1.

• Intensive behavioral interventions focusing on language, play, and social communication skills are first-line therapy 1.
• Pharmacotherapy is reserved for co-occurring conditions and specific symptoms, not core ASD features 1.
• Delay in treatment while seeking additional opinions can negatively impact long-term developmental outcomes 5.

Genetic Counseling and Recurrence Risk

Provide genetic counseling to the family regardless of whether genetic testing identifies an etiology, as this addresses family planning concerns and helps families understand ASD 3, 1.

• Full sibling recurrence risk is 3-10% overall 1.
• Risk is modified by sex: 7% if the affected child is female, 4% if male 1.
• With two or more affected children, recurrence risk is at least 30% 1.

Critical Pitfalls to Avoid

• Do not delay diagnosis or treatment seeking multiple opinions when a qualified evaluation using standardized measures has confirmed ASD 1, 5.
• Do not order extensive genetic testing without clinical geneticist evaluation first, as the stepwise approach is more cost-effective 3, 1.
• Do not fail to rule out hearing loss with formal audiogram before attributing all symptoms to ASD 3, 1.
• Do not assume that a negative first assessment invalidates a positive second assessment - false negatives are common in ASD evaluation, particularly in younger or higher-functioning children 2, 5.