Children with DiGeorge syndrome, a disorder characterized by the deletion of several genes on the 22nd chromosome, have a significantly higher risk of developing either psychosis or autism spectrum disorder. But, until now, there has been no way to predict which path a child with DiGeorge might follow.
In a new study, researchers at the University of California, Los Angeles (UCLA) and the University of Pittsburgh are the first to suggest a potential way to make that determination in patients with DiGeorge syndrome, also known as 22q11.2 deletion syndrome. They report having isolated specific genetic differences between those with autism and those with psychosis.
Between 30 and 40 percent of individuals with DiGeorge syndrome are diagnosed with a disorder on the autism spectrum, and between 25 and 30 percent are diagnosed with a psychotic disorder. A small number are diagnosed with both autism and psychosis.
“Ultimately, this kind of information could be used as a diagnostic tool that could allow pediatricians or other clinicians to determine who will develop which disorder, so that the appropriate intervention can be applied — and applied early enough to have the most impact,” said Dr. Carrie Bearden, the study’s senior author and a professor of psychiatry and psychology at UCLA.
“We know that early intervention is very important for people at risk for autism or psychosis.”
DiGeorge syndrome is the second most common genetic abnormality after Down syndrome, affecting approximately 1 in 2500 children born worldwide. Children with DiGeorge often have elongated faces, almond-shaped eyes and unusual outer ears. They frequently have palate abnormalities, including cleft palate, and they are at elevated risk for cardiovascular defects.
“The hope is that eventually we could identify individuals at risk for either disorder with a blood sample,” said lead author Maria Jalbrzikowski, Ph.D., who was a postdoctoral fellow in Bearden’s lab while they were conducting the study.
For the study, the researchers took blood samples from 46 UCLA patients with the deletion. They also took blood samples from 66 control subjects. They analyzed the samples using a new technique developed by UCLA geneticist Steve Horvath, Ph.D., that allows researchers to look for patterns of genes that are connected to one another.
The analysis determined whether specific gene expression patterns were associated with psychosis or autism.
On average, people with DiGeorge syndrome and psychosis had 237 genes that showed a different pattern from the genes of people with the syndrome but without psychosis. Most of these genes were connected to the regulation of gene expression; that is, the way that genes end up being read as an individual develops.
“Having one chunk of DNA missing appears to cause downstream effects, with other functions becoming disrupted,” said Bearden.
The researchers compared the genes associated with psychosis in the UCLA group of DiGeorge syndrome patients with psychosis to those of a sample of 180 Dutch patients who had been diagnosed with schizophrenia but did not have the syndrome. They found an overlap of seven genes.
“This finding is really important because it provides proof that altered gene expression patterns in those with DiGeorge syndrome and psychosis are shared with people who are diagnosed with schizophrenia but do not have the deletion,” Bearden said. “The same pathways are affected.”
The seven overlapping genes play a role in fetal brain development, suggesting that psychosis may originate during the early stages of brain development, Bearden said.
DiGeorge syndrome patients with autism differed from their counterparts without autism in the expression of 86 genes, which are likely involved in the development of the immune system.
The findings are published in the journal PLOS ONE.