Science Overview

Autism Spectrum Disorder Background

Autism Spectrum Disorders (ASDs) are pervasive development disorders that are characterized by impairment in language and socialization as well as restricted and repetitive behaviors. According to the Centers for Disease Control, the prevalence among eight year olds is approximately 1%.   

The CDC notes that the average age of diagnosis is 4.5 years, yet age of first concern is 19 months. Early diagnosis leads to early treatment – and early treatment is believed to yield better outcomes. Today, ASDs are diagnosed using a variety of assessments that combine direct patient observation and medical history. ASD diagnosis is often made by developmental pediatricians and other specialists after careful assessment using criteria spelled out in DSM-5. In larger developmental medicine centers, children are often seen by a team of experts including developmental pediatricians, speech and hearing specialists, neurologists, psychologists, psychiatrists and occupational therapists.  

Gene Expression Approach

Altered RNA expression between ASD and normal individuals using RNA samples derived from peripheral blood was first proposed in 2006 by Valerie Hu. Using lymphoblastoid cell lines (LCLs) established from peripheral blood leukocytes available through the Autism Genetic Resource Exchange (AGRE), Hu and her colleagues identified gene expression signatures that differentiate between ASD and normal twins, between affected and unaffected sibling pairs, and among individuals with different idiopathic ASD diagnoses and unaffected relatives. Similarly, Geschwind and colleagues showed shared and altered expression signatures from different forms of autism involving known chromosomal copy number imbalances using LCL RNA from the AGRE collection.

In gene expression studies using RNA derived from whole blood and natural killer (NK) cells isolated from whole blood, researchers at the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at UC Davis have demonstrated gene expression changes between normal and autistic children. Most recently, Kohane, Kunkel and colleagues from Children's Hospital Boston have undertaken a large gene expression study comprising 400 ASD cases and controls and have identified a signature that has robust classification accuracy.

These data suggest that differential expression of certain genes in blood cells may form the basis for an ASD biomarker.  All studies conducted to date have been research studies to distinguish typical development from autism spectrum disorders.    

SynapDx is working to further investigate the ability of an RNA-based blood test to differentiate between patients referred for developmental concern to a specialty center.   The goal is to successfully distinguish between patients with ASDs versus those with other developmental disorders using gene expression in a prospective clinical study.  Additional research will be conducted before this test will become widely available. 

Please refer to Publications for citations.