Boys are more likely to be diagnosed with neurodevelopmental disorders, such as autism, because girls need more extreme genetic mutations to develop them, according to a study published in the American Journal of Human Genetics today.
“One of the greatest mysteries in child development, is why so many more males are diagnosed with developmental disorders compared to females,” said Andrew Whitehouse, head of the autism research team at the Telethon Institute for Child Health Research at the University of Western Australia.
Boys are more likely to develop autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. The study authors highlight that one girl is diagnosed with autism for every four boys, while 30% more boys have intellectual disability than girls.
Genetics as well as a possible social bias that increases the chances of diagnosis in boys have both been suggested as reasons for the difference. Boys may simply be tested more frequently for such disorders, leading to higher rates of diagnoses.
Jozef Gecz, professor of human genetics at the University of Adelaide, who has previously worked with one of the researchers but was not involved in this study, said although this research doesn’t identify a social explanation for the gender difference in the diagnoses of neurodevelopmental disorders, the social bias might still be a real effect.
“There are historical, religious and social reasons that, to some extent, would lead to more men being identified with such problems,” he said. “While we don’t see as much of this in modern western societies, there are still glimpses of it.”
But the study authors, Sébastien Jacquemont of the University Hospital of Lausanne and with Evan Eichler of the University of Washington School of Medicine, suggest the size of the difference may be attributable to genes.
They analysed DNA samples and sequencing data sets of one group consisting of nearly 16,000 individuals with neurodevelopmental disorders and another with about 800 families affected by autism spectrum disorder. They studied the individual variations in the number of copies of a particular gene as well as sequence variations affecting single genes.
They found females diagnosed with autism or another neurodevelopmental disorder had both a larger number of harmful individual variations and sequence variations than similarly diagnosed males.
“The data indicate that females require greater ‘aetiological burden’ than males – that is, more genetic mutations – for brain development to be knocked off the typical course (as is the case for autism),” said Andrew Whitehouse.
The authors suggest this is because women are more developmentally robust and require more extreme genetic mutations to push them over the diagnostic threshold. Women can accumulate more genetic damage before they present with neurodevelopmental disorders.
“There are good evolutionary reasons to protect women because they’re the ones who carry the species,” said Gecz. “But these females who survive and have children who may then inherit the mutations.”
“Our findings may lead to the development of more sensitive, gender-specific approaches for the diagnostic screening of neurodevelopmental disorders,” Jacquemont told Cell Press, the publisher of American Journal of Human Genetics.
But Gecz said the question of what proportion of the mutations leading to neurodevelopmental disorders coming from mothers remained. He said working out the significance of the mechanism would also have huge ramifications on diagnostic testing.
Whitehouse noted that the next great mystery was to understand why males were more genetically fragile than females.
“Do females have some form of biological ‘shield’ that males do not, which protects against a certain number of genetic mutations during brain development? Or is that males have an additional biological mechanism that females do not, which may increase fragility to genetic mutations?” he asked.
Understanding these questions, may very well get to the very heart of what causes various types of autism and other neurodevelopmental disorders, he said.