Distinguishing Autism Spectrum Disorder from Down Syndrome

Diagnostic Evaluation

The American Academy of Pediatrics recommends a comprehensive diagnostic evaluation for Autism Spectrum Disorder (ASD) using standardized diagnostic tools, such as the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R), for individuals with suspected ASD, including those with Down syndrome 1, 2.
Down syndrome should be immediately apparent or ruled out through physical examination and genetic testing, as it is a chromosomal disorder with characteristic dysmorphic features that are typically identified at birth or early childhood, with a diagnosis confirmed through genetic testing (karyotype showing trisomy 21) 3, 4.
The diagnostic evaluation for ASD should include a multidisciplinary team assessment, comprising a psychologist, speech/language pathologist, and physician (developmental pediatrician, neurologist, or child psychiatrist), to conduct comprehensive evaluations using standardized diagnostic tools, such as ADOS-2 and ADI-R, with a sensitivity of 91% and specificity of 76% for ADOS-2, and a sensitivity of 80% and specificity of 72% for ADI-R 1, 2.

A formal audiogram should be conducted to rule out hearing loss that could mimic ASD symptoms, as children with significant hearing loss have difficulties with socialization and communication that may be misidentified as autism, with a recommendation for a comprehensive evaluation by a multidisciplinary team, including a psychologist, speech/language pathologist, and physician 3, 6, 7, 2.
Cognitive testing should be performed to establish a baseline developmental level, expecting considerable scatter in results with possible splinter skills, with a recommendation for a comprehensive evaluation by a multidisciplinary team, including a psychologist, speech/language pathologist, and physician 3, 4, 1.

A genetic consultation should be offered to all individuals with ASD, as thorough evaluation identifies an underlying etiology in 30-40% of individuals, with a recommendation for a stepwise approach to genetic testing, starting with first-tier tests, such as chromosomal microarray (CMA) and fragile X DNA testing, and proceeding to second-tier tests, such as MECP2 gene testing and PTEN gene testing, based on specific clinical features 7, 2.
First-tier genetic testing, including CMA and fragile X DNA testing, should be ordered initially, with a diagnostic yield of 10% for CMA and 1-5% for fragile X DNA testing, and a recommendation for a stepwise approach to genetic testing, with higher-tier tests having greater diagnostic yield, and a cost-effective and better-tolerated approach for families 2, 7.

Intensive behavioral interventions based on applied behavior analysis are recommended as first-line therapy for ASD, particularly for children 5 years or younger, focusing on improving language, play, and social communication skills, with small to medium effect sizes, and a recommendation for up to 40 hours per week of therapy 1, 2.
Pharmacotherapy should be reserved for co-occurring conditions and specific symptoms, not core ASD features, with a recommendation for screening for comorbid psychiatric conditions, including ADHD, anxiety disorders, and mood disorders, which occur in approximately 75% of children with ASD 2, 1.

Genetic counseling should be provided to all families, regardless of whether an etiology is identified, with a recommendation for empiric recurrence risk data, including a full sibling recurrence risk of 3-10%, and a modified risk based on sex, with a 7% risk if the affected child is female and a 4% risk if the affected child is male 2.
Periodic reevaluations should be scheduled for patients without a definitive etiology, as diagnostic technology and understanding continue to evolve, with a recommendation for a stepwise approach to genetic testing, and a cost-effective and better-tolerated approach for families 2.