Genetic Test May Help Assess Autism Risk in Siblings of Affected Children

Katherine A Kahn, DVM

October 14, 2008

October 14, 2008 (Boston, Massachusetts) — A multigene risk assessment test for autism in families that already have an affected first child may help to predict the risk of developing the disorder in siblings, a new study concludes.

Jorg Hager, PhD, and Geraldine Dawson, PhD, jointly presented the findings of their research and its implications here at the American Academy of Pediatrics 2008 National Conference and Exhibition. Dr. Hager is the chief scientific officer of IntegraGen SA, the company that developed the test. Dr. Dawson is the chief scientific officer of Autism Speaks and serves on the advisory board of IntegraGen SA.

Using data on 226 families from the Autism Genetic Resource Exchange, researchers genotyped single nucleotide polymorphisms (SNPs) in the PITX1, ATP2B2, SLC25A12, and EN2 genes in families that had at least 2 children and at least 1 child with autism. Siblings unaffected by autism served as a control group.

The frequency of single SNP risk alleles in the 4 genes and the odds ratios for increasing numbers of risk alleles were calculated. "The risk of autism increases with increasing numbers of risk alleles," Dr. Hager told session attendees. The average increase per risk allele was 1.35 (90% confidence interval [CI], 1.14 – 1.59; P = .002); however, if a child carried the maximum number of 8 risk alleles, the odds ratio was 5.94 (90% CI, 2.16 – 16.32).

"We wanted to introduce a risk threshold, so we classified those children as high risk who have at least 7 risk alleles," Dr. Hager said. "When you reduce the threshold to at least 7 risk alleles then the chance of being autistic increases by 2." The specificity of the test was determined to be 92%, while the sensitivity was 16%.

Dr. Dawson elaborated on some of the potential benefits of the risk assessment test. "This is a tool that a physician could use to assess whether an infant [with an autistic sibling] might be at higher risk for autism. This could be used before symptoms emerge so that greater vigilance and monitoring can occur for that infant, or the test could be used when we start to see the emerging red flags," she said.

Dr. Dawson also pointed out that the test could help lead to earlier intervention. "Early intervention does affect outcome," she told session attendees. "There have been studies of early intensive intervention for children 2 to 4 years of age that shows intervention can have a significant impact on outcome."

She also stressed that this test was not diagnostic for autism, but it could complement existing clinical tools in evaluating children at risk for the disorder. "We are moving into a new era now," she said. "There are significant ethical issues that come with moving in this direction that are inevitable."

Alex Kemper, MD, MPH, commented to Medscape Pediatrics about the study. "Although on first blush the sensitivity of the test is disappointingly low, the specificity may have more important implications," he said. "The fact that the specificity for this test is 92% means there is an 8% chance that if a child didn't have autism, they would test positive for it. That could be devastating for a family, especially in light of Dr. Dawson's comments that a positive test could allow for increased monitoring and early intervention.

"It's important to consider the potential downside to these types of tests," Dr. Kemper continued. "We know from studying other serious pediatric conditions that even after a false-positive is uncovered as false, families continue to worry." Dr. Kemper, an attendee at the conference, is a general pediatrician at Duke Pediatrics, in Durham, North Carolina.

The study was funded by IntegraGen SA, Evry, France.

American Academy of Pediatrics 2008 National Conference and Exhibition: Abstract 578. Presented October 12, 2008.

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