CHICAGO -- Think autism and an image of an awkward boy typically emerges, but the way autism strikes girls -- or doesn't -- may help reveal some of the developmental disorder's frustrating secrets.

Autism 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 do not show symptoms of autism even when they have the same genetic mutations seen in boys with the condition.

"Autism may not be the same thing in boys and girls," said Kevin Pelphrey, an autism researcher at George Washington University.

The causes of autism aren't known. Genetic mutations are thought to play a role, and outside factors including older parents and premature birth also have been implicated. But the gender effect is now 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.

WHAT SCIENCE SHOWS

Brain imaging suggests there may be an additional explanation for why many girls with autism have more subtle symptoms than boys, Pelphrey said. Even in girls who clearly have autism, he said, brain regions involved in social behaviour that are normally affected are less severely impaired.

Also, recent studies on autism-linked genes have found that girls can have the same kinds of genetic mutations seen in boys with autism, but not show symptoms. They "even need to have twice as many mutations on average to actually manifest with autism," said Joseph Buxbaum, director of an autism centre at Mount Sinai medical school in New York.

He 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.

AUTISM SISTERS PROJECT

Buxbaum is involved in the Autism Sisters Project, which is seeking to enrol hundreds of families with autistic sons but unaffected daughters. The project began last year with the goal of building a big database that scientists can use to look for genetic clues and protective factors. 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 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.

Her focus is "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 behaviour 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."

MAKING A DIAGNOSIS

Autism is diagnosed by observing behaviour, there's no blood test for it. Some experts say gender-based differences highlight a need to develop different ways to evaluate boys and girls.

Autism screening, recommended for kids starting at 18 months, uses tools based on research in autistic boys, said Rachel Loftin, clinical director of an autism centre at Rush University Medical Center in Chicago.

One widely used screening questionnaire for parents includes questions like "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 behaviour therapy that is the main treatment for autism.

Some girls manage to camouflage symptoms until pressures to fit in at school become overwhelming, delaying diagnosis until around age 8 or 9, said Alycia Halladay, chief science officer at the Autism Science Foundation, a non-profit educational and research-funding group which is paying for the Sisters Project.

The prominent autism advocate, professor and author Temple Grandin wasn't fully verbal until age 4. "It was obvious something was drastically wrong with me," Grandin said. But she said she learned to adapt, in part because with "1950's parenting" she was faced with intense encouragement to develop social skills and other talents.

PARENTS' CONCERNS

Allison Klein worried about her daughter, Jillian, for three years before the little girl was finally diagnosed with mild autism. Jillian couldn't tolerate loud noises, she grew withdrawn around her preschool classmates and she lagged behind academically. She was labeled anxious, not autistic.

"She didn't meet the stereotypical behaviours of no eye contact, no communication, hand flapping," Klein said. Teachers and doctors suggested she was just shy and would grow out of it.

A few months ago, just before Jillian turned 6, Loftin confirmed Klein's concerns.

Even Pelphrey, the autism researcher, had a similar experience. His daughter, Frances, was diagnosed almost four years after her behaviour raised concerns. She didn't walk or talk until she was almost 3 years old. She tried to be "cuddly" and interact with others, but sometimes she did so awkwardly.

"Nobody really wanted to make the call," Pelphrey said. "Had she been a boy, there would have been much more pressure to look into it."