Researching the genetics of an autism spectrum disorder (ASD) is a bit like detective work for Daniel Moreno De Luca, MD, MSc.
The fourth-year resident in the Yale Department of Psychiatry said tests can identify genetic abnormalities highly associated with ASD, and that can translate into better treatment plans for the patient, and a sense of resolution for parents.
However, genetic testing for people with ASD – despite being an accepted standard of care -- remains the exception rather than the norm.
At the Hospital for Special Care in New Britain, where Moreno De Luca helped develop an autism-genetics clinic, approximately 80 children have undergone genetic testing so clinicians can attempt to better understand the reason behind their ASD diagnosis. That number represents a mere fraction of the thousands of children in Connecticut who have been identified as exhibiting the disorder.
Moreno De Luca wants to change that. He is advocating for more children to undergo tests to identify genetic abnormalities that are highly associated with ASD.
“By knowing what the genetic cause is, we can have a better idea of the neurobehavioral profile of the kids,” Moreno De Luca said. “This will help people understand the cause behind the ASD diagnosis, and help to develop specific treatment recommendations.”
ASD is a developmental disorder, and its symptoms include difficulty with social interaction and communication, and repetitive behaviors and interests, starting early in childhood. There is no known single cause; instead, research points toward a strong genetic basis with multiple diverse genetic anomalies increasing risk for the condition.
Chromosomal microarray testing, considered medically necessary in the clinical workup of children with ASD, tests for an altered amount of genetic material, including deletions (where an area of the chromosome is missing) and duplications (where an area of the chromosome is present in extra amounts). “The genetic cause of autism may be different in every child,” Moreno De Luca said. “The results of the tests, if abnormal, explain the autism in that person. Although you cannot generalize for this to everyone, in those specific cases, we’re able to know.”
Genetic testing can explain an ASD diagnosis in up to 30 percent of cases, Moreno De Luca said. “The number is increasing more and more,” he said, crediting improvements in technology, including whole exome and whole genome sequencing.
The autism-genetics clinic, housed within the Autism Clinic in the Hospital for Special Care in New Britain, swiftly integrates with the new Autism Inpatient Unit, which opened late last year. The facility is the first of its kind in Connecticut; it provides care for children with an ASD diagnosis who need treatment for aggression, self-injury, or severely impaired functioning.
Patricia Aguayo, MD, MPH, the unit’s medical director, said genetic testing continues to be the exception, however more parents are opting to have their children screened.
“We’re so busy I can’t even tell you,” she said. “We need to group together these cases to determine what these children have in common.”
Some parents approach testing with trepidation, fearing that a genetic anomaly they passed to their child may have resulted in the ASD diagnosis, she said. Others feel a sense of relief in knowing their child’s diagnosis was genetically based, and not a result of something that may have occurred during pregnancy, Moreno De Luca said.
He said pinpointing a genetic abnormality also helps to connect parents on a social level with other families whose children have similar genetic findings.
Clinicians should be better able to manage a child’s treatment plan and medication if they know a child’s genetic profile, he said. “Besides allowing us to identify the children’s potential areas of impairment and medical comorbidities, it also helps to identify other potential strengths,” he said. “There are many hidden therapeutic strategies one can implement, guided by the genetics results.”
Rebecca Muhle, MD, PhD, a sixth-year resident in the Solnit Integrated Training Program at Yale, shares Moreno De Luca’s interest in ASD, and has written about the disorder. Along with Aguayo and Moreno De Luca, she helped start the autism genetics clinic and will join Aguayo’s program in July when she finishes at Yale. She said she looks forward to continuing to educate parents about the value of genetic testing.
“Genetic testing is a standard of care in this population, but the word really has not gotten out,” she said. “We need to approach the clinical population with the understanding of how and why genetic testing can be valuable. It takes individual cases to show how genetic testing can be helpful.”
She said Moreno De Luca has stressed to his fellow psychiatry residents why testing is important, and how to implement it in a clinical setting.
“Daniel was one of the first people to make a connection between how genetic variations can be applicable,” she said. “He presented it in such a way to make it relevant to the clinical population.”
Moreno De Luca will continue his education next year at Brown University, where he will do a fellowship in child and adolescent psychiatry. He will maintain ties with the Hospital for Special Care and Yale while he pursues his work in genetics research.
"I'm very excited to see this take shape more and more," he said. "Genetics is playing a larger role in all aspects of medicine. You can use the information obtained from testing to better manage a patient's clinical care, very much in line with other efforts in precision medicine."