Newer genetic testing methods may provide benefit for children with suspected autism

September 01, 2015

The use of two newer diagnostic testing technologies (chromosomal microarray analysis and whole-exome sequencing) among children with autism spectrum disorder are superior to current approaches of identifying genetic mutations linked to the disorder, according to a study funded in part by Autism Speaks.  The study also found that children with certain physical anomalies were more likely to have detectable genetic mutations, findings that may help identify children who could benefit most from genetic testing.

The study appears in the September 1 issue of JAMA.  It was led by Dr. Stephen Scherer, of the Hospital for Sick Children, Toronto, who is director of the Autism Speaks MSSNG program.

Scherer and colleagues performed chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a group of 258 unrelated children with ASD to determine the percentage of subjects with a genetic alteration [mutation] that may contribute to the features of autism spectrum disorder present in these individualsof these tests. All children underwent CMA; a random subset of 95 also underwent WES. All children underwent detailed clinical assessments for the presence of any major congenital abnormalities and minor physical anomalies and were stratified into 3 groups of increasing severity: essential, equivocal, and complex.

Of the 258 children, 24 (9.3 percent) received a molecular diagnosis from CMA and 8 of 95 (8.4 percent) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic cause was 15.8 percent. This included 2 children who received molecular diagnoses from both tests. The clinical yield for genetic testing was much higher (37.5 percent) in children with ASD who had more complex clinical presentations based on physical examination.

“The researchers demonstrate that modern diagnostic tools can greatly increase the ability to identify genetic causes for a subset of people with autism spectrum disorder.  The ability to get this information into the hands of families and clinicians is critical.   The results from the type of tests used in this study allow for a more informed and individualized treatment plan that can only be developed by knowing the specific genetic causes and associated risk factors,” said Dr. Mathew Pletcher, vice president and head of genomic discovery at Autism Speaks.