Pathogenic Yield of Genetic Testing in Autism Spectrum Disorder

Pediatrics. 2020 Oct;146(4):e20193211. doi: 10.1542/peds.2019-3211. Epub 2020 Sep 16.


Background and objectives: Genetic testing is recommended for individuals with autism spectrum disorder (ASD). Pathogenic yield varies by clinician and/or patient characteristics. Our objectives were to determine the pathogenic yield of genetic testing, the variability in rate of pathogenic results based on subject characteristics, and the percentage of pathogenic findings resulting in further medical recommendations in toddlers with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASD.

Methods: We conducted a retrospective chart review of 500 toddlers, 18 to 36 months, diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (mean age: 25.8 months, 79% male). Subject demographics, medical and neuropsychological characteristics, and genetic test results were abstracted. Genetic results were divided into negative or normal, variants of unknown significance, and pathogenic. Subject characteristics were compared across results. Manual chart review determined if further recommendations were made after pathogenic results.

Results: Over half of subjects (59.8%, n = 299) completed genetic testing, and of those, 36 (12.0%) had pathogenic findings. There were no significant differences in Bayley Scales of Infant Development cognitive (P = .112), language (P = .898), or motor scores (P = .488) among children with negative or normal findings versus a variant of unknown significance versus pathogenic findings. Medical recommendations in response to the genetic finding were made for 72.2% of those with pathogenic results.

Conclusions: Our findings reinforce the importance of genetic testing for toddlers diagnosed with ASD given the 12% yield and lack of phenotypic differences between subjects with and without pathogenic findings. The majority of pathogenic results lead to further medical recommendations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / diagnosis
  • Autism Spectrum Disorder / genetics*
  • Body Dysmorphic Disorders / diagnosis
  • Body Dysmorphic Disorders / genetics
  • Child, Preschool
  • Chromosomes, Human, 13-15
  • Cognition
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Gene Deletion
  • Gene Duplication
  • Genetic Testing / methods
  • Genetic Testing / statistics & numerical data*
  • Humans
  • Infant
  • Language Development
  • Male
  • Microarray Analysis
  • Mosaicism
  • Motor Skills
  • Mutation
  • Phenotype
  • Referral and Consultation
  • Retrospective Studies


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein