CHICAGO >> Think autism and an image of an awkward boy typically emerges. The developmental disorder is at least four times more common in boys, but scientists taking a closer look are finding some gender-based surprises: Many girls with autism have social skills that can mask the condition. And some girls are born without autism despite the same genetic mutations seen in boys with the condition.
The gender effect is a hot topic in autism research and one that could lead to new ways of diagnosing and treating a condition that affects at least 1 in 68 U.S. children.
Better understanding of gender’s role is key to helping the most people, said Kevin Pelphrey, an autism researcher at George Washington University. “Autism may not be the same thing in boys and girls.”
What science knows
The causes of autism aren’t known, but various genetic mutations are thought to play a role, and outside factors including older parents and premature birth also have been implicated.
Brain imaging suggests there may be an additional explanation for why many girls with autism have more subtle symptoms, Pelphrey said.
“The surprising thing we are finding is that even in girls who clearly have autism,” brain regions involved in social behavior that are normally affected are less severely impaired, he said.
Recent studies on autism-linked genes have found another gender difference.
Girls can have the same kinds of genetic mutations seen in boys with autism, “and even need to have twice as many mutations on average to actually manifest with autism,” said Joseph Buxbaum, director of an autism center at Mount Sinai medical school in New York City.
Buxbaum is among researchers trying to identify a “protective factor” that may explain how some girls at genetic risk remain unaffected, perhaps a protein or other biological marker that could be turned into a drug or other therapy to treat or even prevent autism. That possibility is likely a long way off, but Pelphrey said this line of research has prompted excitement among autism scientists.
Making a diagnosis
There’s no autism blood test. It’s diagnosed by observing behavior and some experts say gender-based differences highlight a need to develop different ways to evaluate boys and girls.
Autism screening is recommended for all kids at age 18 months and 2 years. But screening tools typically are based on research in autistic boys, said Rachel Loftin, clinical director of an autism center at Rush University Medical Center in Chicago.
One widely used screening questionnaire for parents focuses on social deficits seen more often in autistic boys than affected girls. Questions include “Does your child play make-believe, make eye contact, seek praise, show interest in other children?” Girls with autism, especially mild cases, often don’t show obvious problems in those categories — they’re more likely than affected boys to play pretend with toys rather than lining them up by size or shape. Loftin said they’re also more likely to show concern for another person’s feelings.
Government data show that all forms of autism — mild to severe — are more common in boys and that the average age at diagnosis is 4 years in boys and girls. But Loftin said anecdotal evidence suggests a two-year lag time in diagnosis for girls, especially those with mild cases. And she suspects many cases are missed or misdiagnosed. That means a delay in early intensive behavior therapy that is the main treatment for autism.
Some girls manage to camouflage symptoms until school pressures to fit in become overwhelming, delaying diagnosis until around age 8 or 9, said Alycia Halladay, chief science officer at the Autism Science Foundation, a nonprofit educational and research-funding group.
A mom’s concern
Allison Klein worried about possible autism in her daughter, Jillian, for three years before the little girl was finally diagnosed. Jillian couldn’t tolerate loud noises, grew withdrawn around her preschool classmates and lagged behind their academic progress. She was labeled anxious, not autistic.
“She didn’t meet the stereotypical behaviors of no eye contact, no communication, hand flapping,” Klein said. “It was always the hands-off approach from teachers and doctors.”
“They’d say, ‘Let’s wait and see. Give her some time, she’ll grow out of it. She’s just shy,’” Klein recalled. “People dismiss it in girls.”
A few months ago, just before Jillian turned 6, Rush University’s Loftin confirmed Klein’s concerns. Jillian has mild autism. Now the family is playing catch-up in getting her needed services.
Siblings and autism
Buxbaum, the Mount Sinai researcher, is seeking to enroll hundreds of families with autistic sons but unaffected daughters in a study looking for genetic clues and protective factors. Funded by the Autism Science Foundation, the Autism Sisters Project began last year with the goal of building a big database that other scientists can use. Girls and their families visit the New York lab to give saliva samples for DNA analysis and efforts are underway to expand DNA collection to other sites.
Evee Bak, 15, hopes her saliva samples will eventually benefit her older brother Tommy. The suburban Philadelphia siblings are just a year apart. They play in a garage band— Evee on drums, Tommy on guitar and vocals. He’s a masterful musician, but has trouble reading social cues and doing things that come easy to other teens, like shopping alone or using public transportation.
“The thing at the forefront of my mind is mostly just taking care of Tommy and making sure he’s happy and healthy,” Evee said.
Tommy was diagnosed at age 3, after he stopped using words he’d learned months earlier and showed unusual behavior including repetitively lining up toys instead of playing with them.
“He’s a wonderful person and I don’t think that we’d ever want to change him,” said his mother, Erin Lopes. But they’d welcome anything that could help him function as independently as possible “because I think that’s what he really wants, is to be independent.”