Autism spectrum disorders are roughly five times more common in boys than girls, for reasons which have long eluded doctors and researchers.
Now, a new study lends support to the so-called "female protective model," which suggests it takes more extreme genetic mutations to produce symptoms of autism or neurodevelopmental disorders in girls than in boys.
"Females require more mutational 'hits' to push them over into a state of autism, intellectual disability or developmental delay," Evan Eichler, a professor of genome sciences with the University of Washington and an author on the study, told The Huffington Post. The findings were published in the American Journal of Human Genetics on Thursday.
Eichler and colleagues analyzed DNA samples of more than 15,000 boys and girls with neurodevelopmental disorders, and just under 800 who had been diagnosed with an autism spectrum disorder.
They looked for what Eichler called "really bad" gene mutations, things like copy-number variants (changes in the number of copies of a particular gene) and single nucleotide variants (DNA sequence variations that affect a single nucleotide).
Girls who had been diagnosed with neurodevelopmental disorders and autism spectrum disorder had more harmful mutations than boys. Therefore, the theory goes, girls' brains may need more mutational "hits" to push them over into a state of autism, intellectual disability or developmental delay.
Researchers have been exploring the idea of a genetic female protective effect against autism and other developmental issues for years, though Eichler said for the last decade efforts have focused largely on the X chromosome as the basis for sex-based differences (females have two X chromosomes; males have one X and one Y). The new study joins a growing body of research looking not just at the X chromosome, but the entire genome, he said.
But there is also the possibility that experts are simply less likely to recognize symptoms of autism in girls. For example, one study, published in November in the Journal of the American Academy of Child and Adolescent Psychiatry, argued that girls may be developing strategies to compensate for autism-like behaviors, such as difficulties recognizing emotion, and may require subtler diagnostic criteria.
Eichler said that the new study does not "solve" anything, but he hopes the findings help fit one more piece in a complex puzzle.
"As geneticists, we want to start identifying the actual, specific genes that matter," he said. "Simply saying, 'There's an excess burden of big deletions or mutations' is fine, but it doesn't really help at a practical level ... What we really want to do is to be able to say, 'These specific genes will actually increase the risk of autism in a child.'"