Autism is a complex developmental disorder, and diagnosing it properly usually involves a combination of different tests. In the latest issue of JAMA, scientists provide the most up-to-date assessment yet of which tests work best for detecting genetic mutations associated with certain kinds of autism. Categorizing the various forms of autism will be important to guide parents to the proper care, the researchers say.

Traditionally, autism is diagnosed with behavioral tests that assess whether kids are meeting developmental milestones, such as talking, interacting with their parents and siblings, and learning to give and take in social situations. In recent years, researchers have been working on other ways to detect and potentially diagnose autism. Scientists have identified more than 100 genes connected with a higher risk of developing autism.

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Stephen Scherer, director of the center for applied genomics and a professor at the Hospital for Sick Children in Toronto, and his colleagues conducted a comparison test to see how the genetic tests matched up, both against each other and against the more conventional behavioral evaluations.

They studied 258 children who were diagnosed with autism spectrum disorder; all had a form of genetic testing done that looks specifically at abnormalities in the chromosomes; some had more extensive genetic testing, called whole-exome sequencing.

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The two genetic tests were roughly equally capable—around 8-9%—of detecting autism. Regardless of the fact they perform similarly, however, more labs and clinicians are favoring whole-exome sequencing, says Scherer. That’s concerning because the two genetic tests pick up markers for different kinds of autism, and excluding the other test in favor of the more high-tech whole-exome sequencing would miss about half of the possible genetic predictors of autism. Together the two gene-based tests can diagnose nearly 16% of cases.

“We need to use both technologies now,” he says. “If we only used one, we would miss some important information.”

The tests aren’t cheap. The chromosome-based test costs about $500, and exome sequencing slightly more. Ideally, this research suggests, both tests would be done for any child referred to a developmental pediatricians who suspects autism. But the reality is that for now, insurers may not cover both.

Scherer’s group looked at how non-genetic evaluations matched up with the genetic testing. Using factors such as brain scans to look for physical differences that might indicate autism, they divided the children into three groups based on whether they possessed physical anomalies or not. Among children with more physical abnormalities, the two types of genetic testing together diagnosed autism in 37.5% of cases.

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That suggests that the most accurate diagnosis of autism may come from combining all three types of tests. Not only that, says Scherer, but such testing can also categorize the type of autism that a child may have. “We need to start looking at each autism case individually, and come up with the best recommendations,” he says.

For now, based on the results of the study, he recommends that behavioral testing be the first step. Then, the chromosomal test should be done to see if it yields any additional information about a connection to autism. Even if it does not, that doesn’t mean that there aren’t genetic factors in play. If the chromosomal test is negative, Scherer argues that in some cases the whole exome sequencing might be useful.

Working with genetic counselors can help parents decide if and when this type of genetic testing is needed. “The message is that we need to use all technologies to get as much detailed information as we can to marry them all together,” he says.

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