Advanced genetic testing can help identify discrete forms of ASD

Autism spectrum disorders (ASD) are not completely understood neurodevelopmental disorders diagnosed solely on the basis of behavioral assessments of social, communicative and repetitive symptoms. Though behaviorally distinctive and reliably identified by experienced clinicians, ASD is clinically and genetically extremely diverse, affecting each patient differently. Efforts to identify subsets of patients with similar outcomes and chances of recurrence has been difficult, said Judith Miles, M.D., P.h.D., a University of Missouri child health physician and researcher specializing in medical genetics, in an invited editorial published Sept.1 in the Journal of the American Medical Association (JAMA).

The article discusses the use of cutting-edge genetic testing to sort out genetically discrete forms of ASD. Using chromosomal microarray analysis and whole-exome sequencing, researchers at the University of Toronto tested for genetic mutations in children with autism. Using the subgrouping technique described by Miles in 2005, which separated "complex" from "essential" autism, they were able identify which children were most likely to have a mutation. Children with "complex autism" were diagnosed with a known mutation 37.4 percent of the time, compared with only 4.2 percent for children with "essential autism." Complex autism is defined by clinically assessing each child for minor congenital anomalies, which are evidence of a disruption in early fetal development.

The newest techniques provide a marked improvement over traditional genetic testing. In fact, Miles believes it may be seven times more informative than chromosomal testing.
"Foremost, the data indicates that physicians responsible for diagnosing children with autism spectrum disorder should arrange genetic evaluations using techniques that have the best chance of determining a conclusive diagnosis," Miles said. "It is undeniable that precise diagnoses pave the way to better medical care, improved surveillance, better functional outcomes and informed genetic counseling."

Although Miles sees a clear need for the new genetic testing, obstacles may include insurance coverage for this type of testing and finding a geneticist in some locations. In these cases, she said, the noninvasive, inexpensive dysmorphology examination — looking for unique or unusual physical characteristics — can help identify children with the highest probability of having an identifiable genetic diagnosis.

"This recent work in ASD diagnosis shows just some of the remarkable strides made over the last decade," Miles said. "The latest research provides an ideal illustration of how broad, symptom-based diagnoses such as autism can and should be dissected into relevant subgroups and transformed into hundreds if not thousands of specific genetic diagnoses. By doing so, each diagnosis will then end up with its own clinical characteristics, potential medical risk factors, ways, rules for handling symptoms and heritability details, and eventually better treatment."