Abstract Details

Title Evaluation of 18,911 Individuals with Autism Reveals that Exome Analysis Provides Higher Diagnostic Rates and Reduced Time to Diagnosis than Traditional Testing Strategies

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 136

Objective Evaluate the time to diagnosis and diagnostic outcome of exome analysis for individuals with autism, with and without comorbidities, and highlight genes not previously associated with autism spectrum disorders (ASD).

Background Roughly 1/59 children have been diagnosed with ASD; however very few large studies have evaluated the genetic basis of autism and current guidelines only recommend exome analysis after significant clinical review and focused genetic testing.

Design/Methods Review of exome analysis from 18,911 (2.4 Male:Female ratio) individuals with autism or autistic behavior, as designated by referring physician, from a commercial laboratory. Syndromic autism was defined as having two or more comorbidities (dysmorphic features, seizures, developmental delay, muscle or skeletal abnormality).

Results Many individuals (89%) had at least one prior genetic test consistent with guidelines: FMR1, arrayCGH, multi-gene panel. Individuals with syndromic ASD had a positive rate of 20.9%, whereas individuals with isolated ASD had a positive rate of 7.8%. Positive findings were identified in 698 genes, 417 of which were absent from the Simon Foundation Autism Research Initiative list. Findings were identified in 1337 emerging genes (did not have an established connection to autism when reported) and 113 of these genes were upgraded to disease-causing over the course of this study.

Conclusions Prior negative testing delayed a positive result for 89% of individuals. The high positive rate for syndromic autism suggests that FMR1 and arrayCGH should be performed after non-diagnostic exome analysis. Additionally, 60% of disease-causing genes in this study are not on the SFARI list and many more were considered emerging at the time of reporting, supporting the use of a broad testing approach, that is not limited to curated gene lists to increase diagnostic results for individuals with autism.

Authors/Disclosures
Amanda S. Lindy, PhD (GeneDx, Inc.) PRESENTER	Dr. Lindy has received personal compensation for serving as an employee of GeneDx.
	No disclosure on file
	No disclosure on file
Paul S. Kruszka, MD (GeneDx)	Dr. Kruszka has received personal compensation for serving as an employee of GeneDx. Dr. Kruszka has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Journal: Molecular Genetics and Genomic Medicine. Dr. Kruszka has received personal compensation in the range of $100,000-$499,999 for serving as a Intramural Investigator 2014-2021 with National Institutes of Health.

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