Researchers call for more extensive screening for genetic conditions related to autism, ID

Two new papers from U.S. researchers call for more extensive testing for genetic conditions related to autism and/or intellectual disability.

In the first paper, Tashalee Brown and colleagues note that while the guidelines of the American College of Medical Genetics call for genetic testing for children with autism spectrum disorders (ASD) or intellectual disabilities (ID), children enrolled in Medicaid or CHIP (a program that provides low-cost health coverage for children in families with incomes too high to qualify for Medicaid) rarely receive this testing.

The researchers analyzed claims for more than 241,000 children enrolled in Medicaid or CHIP between 2008 and 2016, when the children were between seven and 17 years of age. The researchers found that while 26% of children with both ASD and ID received genetic testing, only 17% of children with ASD alone and 13% of those with ID alone were tested. They also found that black children across all diagnostic groups were less likely to receive genetic testing than non-Hispanic white children.

The researchers note, “Genetic testing for children with ASD and ID can have substantial clinical utility and is an essential feature of precision medicine for neurodevelopmental disorders. Knowledge of a specific genetic etiology can provide important information about the risk for associated medical and psychiatric problems and may enable direct changes in medical management, including surveillance regimens, recurrence risk counseling, or syndrome-specific clinical care, research, and support. Furthermore, recent advancements in gene therapies and genetic testing can lead to downstream access to novel therapies.”

In the second paper, Randi and Paul Hagerman, who are experts on fragile X syndrome—the most common single-gene cause of intellectual disability and autism— express concern that too few children currently receive testing for the condition.

The researchers say that all individuals with a diagnosis of autism or intellectual disability should be screened for fragile X. “Unfortunately, this isn’t happening consistently, even though it’s recommended by the leading medical organizations,” Randi Hagerman says. “It’s a simple blood test, which is usually covered by insurance or Medicaid/Medi-Cal, and is absolutely necessary for these conditions.”

Fragile X syndrome is more common in males than in females. It causes symptoms that can include autistic-like speech and language problems, behavioral issues, social anxiety, sensory issues, poor sleep, large ears, a long face, flexible fingers, flat feet, and enlarged testicles in males. Females with fragile X syndrome have milder symptoms than males, due to the protection provided by an additional unaffected X chromosome.

Brown and colleagues say, “Genetic testing for children with ASD and ID can have substantial clinical utility and is an essential feature of precision medicine for neurodevelopmental disorders.”

Fragile X syndrome involves the FMR1 gene on the X chromosome, which produces a protein called FMRP that is essential for normal nervous system function. The syndrome stems from a genetic alteration involving a DNA segment within the gene called the “CGG triplet repeat.” Normally, this segment repeats a small number of times. If it repeats far more often, it can lead to a premutation or to a full mutation that stops the FMR1 gene from producing FMRP and causes fragile X syndrome. The number of repeats can increase over generations, increasing the likelihood of later generations having fragile X syndrome.

The researchers note that one in 150 to 200 women and 1 in 300 to 400 men in the general population carry premutations of the FMR1 gene. Females with the premutation have a 50% chance of passing a premutation or full mutation on to each of their children, while males with the premutation will pass it on to all of their daughters but none of their sons. The more CGG repeats a woman with a premutation has, the more likely it is that her child will inherit an FMR1 gene with a full mutation. (Males will not pass a full mutation on to any of their children.)

The Hagermans’s research has shown that individuals who carry the premutation may develop health conditions themselves, including ovarian insufficiency (which can lead to irregular periods, early menopause, and fertility problems) and fragile X-associated tremor/ataxia syndrome (which causes tremors, balance problems, memory problems, and sometimes symptoms resembling Parkinson’s disease). They also may be at higher risk for autoimmune issues and neuropsychiatric problems such as anxiety and depression.

As a result, the researchers say, a primary diagnosis of fragile X syndrome in an individual with autism or intellectual disability often leads to related diagnoses of other relatives. Thus, they recommend that when an individual receives a fragile X diagnosis, providers obtain a medical history of the full family tree.

Citations

“Medicaid claims from 2008 to 2016 indicate low rates of genetic testing among children with intellectual disability and autism spectrum disorder,” Tashalee R. Brown, Wei-Lin Lee, Jonas Ventimiglia, Audrey Thurm, Tess Levy, Victoria Yuan, Julian A. Martinez-Agosto, and Lindsay L. Shea, Genetics in Medicine, June 2025. Address: Tashalee R. Brown, 1100 Glendon Ave, Suite 900, Los Angeles, CA 90024, [email protected].

—and—

“Genetic testing for children with autism and intellectual disabilities remains rare in Medicaid, despite guidelines,” news release, University of California, Los Angeles, June 18, 2025.

—and—

“The spectrum of fragile X disorders,” Randi Jenssen Hagerman and Paul J. Hagerman, New England Journal of Medicine, July 16, 2025. Address: Randi Jenssen Hagerman, University of California, Davis, MIND Institute, 2825 50th St., Sacramento, CA 95817, [email protected].

—and—

“UC Davis experts call for greater physician awareness and screening of fragile X-related conditions,” news release, University of California, Davis, July 18, 2025.