Genetic Abnormalities Common in Autism-Spectrum Disorder

By Will Boggs MD

September 17, 2020

NEW YORK (Reuters Health) - About one in eight children diagnosed with autism-spectrum disorder (ASD) have pathogenic findings after genetic testing, according to a new study.

"We should continue to recommend genetic testing for all young children with ASD and we should continue to strongly advocate for insurance coverage for this medically necessary genetic testing," Dr. Elizabeth Harstad of Boston Children's Hospital and Harvard Medical School told Reuters Health by email.

Both the American Academy of Pediatrics and the American College of Medical Genetics recommend genetic testing for all patients with ASD. Variations in insurance coverage mean that many children go untested.

Dr. Harstad and colleagues undertook a retrospective chart review of 500 toddlers (aged 18-36 months) with an ASD diagnosis to determine the pathogenic yield of genetic testing and to determine the rate at which pathogenic findings result in subsequent medical recommendations.

Overall, 229 patients (59.8%) completed genetic testing. Those who completed testing were more likely to have dysmorphic features, to be nonverbal, and to have lower language scores and lower scores on parent report of overall adaptive functioning, communication, motor and socialization skills.

Genetic testing was negative or normal in 62.2% of those tested, 25.8% had variants of unknown significance, and 12% had a pathogenic finding, the researchers report in Pediatrics.

Chromosomal microarray (CMA) testing identified pathogenic variants in 27 children (9.0%), while nine children (3.0%) had pathogenic fragile X findings.

There were no significant differences in cognitive, language or motor standard scores or in patient age, insurance, or median household income between patients with pathogenic findings, variants of unknown significance, or normal results.

Among the 27 children with pathogenic CMA findings, 17 (63%) had a medical recommendation made on the basis of their findings, most commonly including education regarding risk and management of potential seizures and seizure monitoring and referrals to subspecialists.

All nine children with positive fragile X results received a further recommendation via referral to a fragile X clinic for genetic counseling and comprehensive care.

"These findings highlight the importance of clinicians recommending genetic testing for all young children with ASD, rather than recommending it only for those who may be most impacted developmentally," Dr. Harstad said.

"In my clinical practice, I have seen the challenges some families have with getting insurance coverage for genetic testing in young children with ASD," she said. "Thus, although we do not know exactly why about 40% of the sample in this study did not get genetic testing completed, I am concerned that insurance barriers may be associated with this. Our findings highlight the need for more consistent coverage of genetic testing for all young children with ASD."

SOURCE: Pediatrics, online September 16, 2020.