Understanding the root causes of autism

autistic child

They are the words no new parent wants to hear: Your child may have autism.

Experts estimate that one in every 150 children will be diagnosed with some form of autism, the most common condition in a group of developmental disorders known as the autism spectrum disorders (ASDs). There is no known cure, and scientists have yet to pinpoint a cause, though it is commonly thought that genetic mutations and environmental factors both play a role.

Identifying the genes responsible has proved challenging. But a pair of new studies spearheaded by geneticists from Penn’s School of Medicine and the Children’s Hospital of Philadelphia have pinpointed a common genetic variation that is often found in children with autism.

The findings, published last month in the journal Nature, have created quite a stir in the autism research community and ultimately may lead to better diagnostic tools for physicians.

“It is very compelling to find evidence that mutations in genes involved in brain interconnections increase a child’s risk of autism, because other autism researchers have made intriguing suggestions that autism arises from abnormal connections among brain cells during early development,” says study leader Hakon Hakonarson, director of CHOP’s Center for Applied Genomics and associate professor of pediatrics at Penn Medicine.

The Penn team looked at genome-wide data from more than 10,000 study participants and determined that children with autism spectrum disorders were more likely than healthy children to have these common gene variants.

“There have been other studies that have tried to get at the genetics of autism,” says Gerard D. Schellenberg, professor of pathology and laboratory medicine at Penn’s School of Medicine. “This is the first common variant that’s reached statistical significance across the entire genome.”

Schellenberg says he first became interested in human genetics as a research tool to get at human diseases in the 1980s at the University of Washington, where he and some colleagues started an autism research program. By collaborating with other teams across the country, they began collecting data on families with multiple people diagnosed with autism.

Believing that inheritance and certain gene mutations increase the risk of a child developing the disorder, Schellenberg and Hakonarson set out to find clues about which genes contribute to this increased susceptibility. What they found was a common genetic variation that increases the risk of a child developing autism, along with a rarer genetic change that contributes to some cases of autism.

“It certainly takes something else—other genes, almost certainly—and probably something else from the environment. So what we found was one of the contributing susceptibility factors,” Schellenberg says.

The findings won’t result in a diagnostic test that can be used in the doctor’s office tomorrow. But it is the first real step in the understanding of the genetics of autism. And with additional information, physicians soon may be able to predict whether an infant is at high risk for the condition.

“The important thing there is that there are behavioral interventions that do make a difference in somebody with autism. If we could start those very, very early in life, maybe they’d have a bigger impact,” Schellenberg says.

Genetic advances also tell scientists what to pay attention to in terms of studying protein molecules, a key for developing new medicines and therapies for complex genetic diseases like autism.

“We need to understand autism on a very molecular level before we can design rational interventions,” Schellenberg says.

“Rational interventions” are the words parents of autistic children dream to hear. But Schellenberg cautions science still has a long way to go.

“It’s hard to say we’re close to a cure. But we’re a little closer now. This is a good first step,” he says.

Originally published on May 21, 2009