Pair of Genetic Tests Beneficial in Autism

Megan Brooks

September 02, 2015

Combining chromosome microarray analysis (CMA) and whole exome sequencing (WES) may benefit children suspected of having autism spectrum disorder (ASD) by revealing genetic mutations potentially linked to ASD, a new study suggests.

The study also suggests that children with certain minor physical anomalies are more apt to have ASD-related genetic mutations, which could help pinpoint which children would benefit most from these tests.

"DNA testing for ASD is starting to make a foothold, but our data show that it should probably become part of the routine clinical workup," Stephen W. Scherer, PhD, of the Hospital for Sick Children, Toronto, Ontario, Canada, told Medscape Medical News.

The study was published September 1 in JAMA.

Two Tests, Higher Diagnostic Yield

To determine the molecular diagnostic yield of CMA and WES, Dr Scherer and colleagues performed CMA in 258 unrelated children with an ASD diagnosis; 27 (10.5%) had Asperger syndrome, 143 (55.4%) had autistic disorder, and 88 (34.1%) had pervasive developmental delay.

CMA showed genetic mutations that might explain the ASD diagnosis in 24 children (9.3%). WES was performed in 95 of the children (and their parents), which revealed genetic mutations in 8.4%.

Among the children who underwent both CMA and WES, the diagnostic yield reached 15.8% (15 of 95 children, including two children who received molecular diagnoses from both tests), the researchers report.

All of the children were assessed for major congenital abnormalities and minor physical anomalies. On the basis of the results, they were placed in one of three groups of increasing morphologic severity: essential, equivocal, and complex, with scores of 0-3, 4-5, and 6 or higher, respectively. The combined yield of CMA and WES was much higher (37.5%) in children with ASD in the complex group than in the children in the essential group (P = .002).

"In many jurisdictions, CMA for genetic copy number variations is routine," Dr Scherer told Medscape Medical News. "For example, at the Hospital for Sick Children in Toronto, we are performing about 1000 such tests per year, and these are covered by our provincial health care/hospital system."

WES, which looks for different kinds of mutations, is now being introduced as well, he noted, but "good data on its effectiveness were not known." The study in JAMA shows that using WES in addition to CMA "doubles the clinical yield."

It is likely that genetic testing of children with ASD will continue to increase, the investigators note in their article. They point to a recent survey gauging interest in ASD genetic testing among parents, which found that 80% said they would want a sibling younger than 2 years to be tested to identify ASD-risk mutations even if the test could not confirm or rule out the diagnosis.

"For some children with positive genetic test results, treatment plans targeting ASD-associated medical conditions can be offered," the researchers say.

Clear Guidance

Dr Scherer told Medscape Medical News that in the current study and in others, "we have advocated that genetic testing become standard for autism because it gives more information to the doctors to fully categorize the disorder so that the best treatment options and programs can be delivered."

He acknowledged, "Like any new information, these data are complex, and we need to do a better job educating doctors and families how to use it, and when and when not to use it, and that is part of what this paper is about."

In an accompanying editorial, Judith H. Miles, MD, PhD, of University of Missouri Health Care, Columbia, says for ASD, as well as for other behaviorally defined disorders, these results "provide clear guidance."

"Foremost, the data indicate that physicians responsible for children with ASD should arrange access to a genetic evaluation using techniques that have the best chance of determining an etiologic diagnosis. It is incontrovertible that precise diagnoses pave the way to better medical care, improved surveillance, better functional outcomes, and informed genetic counseling, often with the possibility of prenatal or preimplantation diagnosis," Dr Miles writes.

The study was supported in part by Autism Speaks, Autism Speaks Canada, NeuroDevNet, and the Canadian Institute for Advanced Research. Dr Scherer holds the GlaxoSmithKline–Canadian Institutes of Health Research Chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children, receives support from serving on the scientific advisory boards of Population Diagnostics and Younique Genomics, receives royalty fees from Lineagen and Athena Diagnostics, and serves on the scientific advisory board of Autism Speaks.

JAMA. 2015;314:879-880, 895-903. Full text, Editorial


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.