A Better Test for Finding Autism Genes?

March 15, 2010— -- A genetic test for autism currently classified as a secondary approach may be able to pick out the underlying causes for the condition at a rate more than three times that of a screening considered to be a first-tier test, according to a new study published in the journal Pediatrics today by the Autism Consortium and Children's Hospital Boston.

Researchers launched the study to compare the newer screening, called chromosomal microarray analysis (CMA), against the tests that the American Academy of Pediatrics currently considers to be first-tier approaches -- G-banded karyotype and fragile X testing. They said they hope the new research will help the test achieve first-line status when it comes to determining the genetic reasons behind autism spectrum disorders.

The CMA test was developed at Children's Hospital Boston in 2006 and has been evaluated over the past few years.

"We think it should absolutely be a first-tier test for autism," said study co-author Dr. David Miller, assistant director of the DNA Diagnostic Laboratory at Boston Children's Hospital. "It is already being used, but it is not being used in every patient all over the country uniformly."

Study co-author Bai-Lin Wu of Harvard Medical School in Boston said CMA allows doctors to find the underlying genetic cause of 7 percent of autism cases.

"From the number itself, 7 percent does not look like a large percentage," Wu said. "However, there are a lot of kids being diagnosed with autism, so it is 7 percent of a very large number."

Specifically, Wu explained, there are about 4 million births every year in the United States. Current statistics from the U.S. Centers for Disease Control and Prevention put the rate of autism spectrum disorders in American kids at slightly less than 1 percent. This would mean that about 40,000 per year would be expected to have autism spectrum disorders.

Wu said the tests currently used as a first-tier test for autism may only detect 2 percent of the genetic abnormalities that could be behind the development of autism -- meaning that using these tests, it may only be possible to identify genetic causes for about 800 of these children. Linking an additional 5 percent of these cases to a genetic cause would mean an explanation for 2,000 more cases of autism each year.

CMA Test Could Find More Autism Genes, Researchers Say

"Compared to [these tests], this one worked more than three times as effectively," Wu said. "This may mean we detect much more genetic changes that we have not been able to find yet."

What this could mean for parents is an end to the guilt that they may have harbored for their child's condition, said another of the study's co-authors, Dr. Leonard Rappaport, chief of the Division of Developmental Medicine at Children's Hospital Boston.

"As in most things in life, people search for the reason why something happened," Rappaport said. "Mothers are still blamed for their children's developmental problems by extended families, and families blame themselves for secret things they do not even reveal to us. As we find diagnoses that cause ASD, people will worry less about things, such as immunizations, despite there being no data to support them."

Autism experts not involved with the study agreed that adding this test to the current battery could help both families and doctors confront the risks and treatment of autism spectrum disorders.

Dr. Nancy Minshew, professor of psychiatry and neurology and director of the University of Pittsburgh's Autism Center of Excellence, said the test could help parents of an autistic child determine the risk of having another child with autism in the future.

Additionally, she said, families who have a child with autism "can benefit from the experience of all the other individuals with that same genetic defect to anticipate the course [of treatment] and to share in the knowledge of what therapies work."

The researchers behind the study were also hopeful that the test could lead to the detection of more genes associated with autism -- and perhaps even begin to explain some of the mysteries behind why these conditions arise in the first place.

"We hope that in the long term, the identifications of specific genetic causes will help us to determine what's going on in the brains of these children," Miller said, adding that one day this knowledge may even lead to specific treatments tailored to the genetic causes of autism from patient to patient.

A Matter of 'When,' Not 'If'

Because the current guidelines do not list CMA as a first-tier treatment, many insurance companies will not pick up the tab for all or part of the screening, which can cost a couple thousand dollars.

Most doctors agreed that even if the test were adopted as a first-tier treatment, it would not mean that the other two tests currently used would become obsolete.

"Because of the intense interest in trying to understand the contribution of gene abnormalities to the occurrence of an ASD, I believe a 7 percent incidence of detected abnormalities is sufficient warrant to make the test a first-line diagnostic test for this condition," said Dr. Ernest Krug, clinical professor of pediatrics at the Oakland University William Beaumont School of Medicine in Royal Oak, Mich. "But I would still do fragile X testing as well."

Still, study co-author Yiping Shen, a neurologist at Massachusetts General Hospital in Boston, said it is only a matter of time before the test will be adopted on a more widespread basis.

"It will happen," Shen said. "It's kind of a matter of when people will accept that."