Investigators explore diagnostic advances in autism and their implications for treatment on CBC's The Current

February 17, 2015

Dr. Evdokia Anagnostou and Dr. Stephen Scherer were interviewed today on the Current, discussing how conceptions of autism diagnosis, research, treatment, and even the description of the disorder itself will change as a result of findings in a recent whole genome analysis study of families involving autistic siblings.

"Autism study finds no two cases are the same, redefining diagnosis" aired a discussion based on a study published online January 26 in Nature Medicine. The study, led by Dr. Scherer, drew from Canadian families with more than one child diagnosed with autism. Multiple insights arise from the discoveries reported in the paper, including the differing genetic makeup found in two-thirds of the siblings in the study, despite their sharing identical diagnoses.

The interview begins with a recorded visit to the home of a family that participated in the recent Nature Medicine study. The two sons, Thomas, 14, and Cameron, 20, "are strikingly different," according to their mother, though they are both diagnosed with a form of low functioning, developmentally disabled autism. The elder son is laid back, non-verbal, does not understand much of what is said to him, and is disinterested in technology, while his younger brother is more animated, has better receptive language skills, and is enthused about computers.

"It's quite interesting," said Dr. Scherer. The early presumption that all forms of autism spectrum disorder are inherited," when the study actually found that more often than not, this is not the case. Currently, 100 genes are thought to play a role in ASD, and Scherer predicts as many as 500 may eventually be identified.

"We only looked at genetic factors that had a large effect, and are only involved in autism," he said. "In two thirds of the kids, at least one kid carried different genetic codes. This makes it critical to understand subtype."

One hundred and eight different subtypes have been identified to date, and whole genome analysis will lead to development of additional subtypes, Scherer said.

Genes will continue to play an important role in diagnosis of these multiple autisms, according to Scherer, who feels the plural is the only way to accurately describe the diversity along the spectrum. This is an exciting time in the field, he said, given that genes involved in ASD make proteins that affect how brain cells communicate and come together.

"We've cracked open the black box," observed Dr. Scherer.

Whole genome analysis points up the importance of looking at gene-environment interactions, according to Dr. Anagnostou, who is directing a number of clinical trials looking at existing and new drugs as potential treatments for core symptoms of ASD. Environmental factors aren't only toxins. The age of the father, a history of infertilitiy, maternal infections during certain periods of pregnancy and rare cases of exposure, such as Thalidomide, affect how genes translate themselves, she said.

It's very important to understand the biologhical pathways that are affected by environmental factors and how they produce different biology, said Dr. Anagnostou, "so that we have new targets for treatments."

Whole genome analysis will provide a sort of Rosetta Stone for gene-environment interaction, added Scherer. "We've come a long way in understanding the genetic underpinnings of ASD, and at the end of the day, we're still going to be talking about genetics."

Talking about genes, or what they reveal, is also critical right now, according to Anagnostou. Up to 25 percent of children with an ASD diagnosis have other significant complications, such as a predisposition to epilepsy or a heart defect. With certain syndromes there are preventive strategies that can be put in place, she said.

The importance of using the right autism label in these cases varies with the audience, added Anagnostou. It will not be important to a cardiologist, but it will be vital to share information about a mutation that impairs heart function. Knowing a child has autism will help a child's teacher to understand challenging behaviours in the classroom, and what to do about them.
Findings from whole genome analysis also have implications for interventions targeting core symptoms such as repetitive behaviours or impariments in social communication. "Current treatments aren't very successful in addressing the biology that underlies them," said Anagnostou.

Going forward, Dr. Scherer predicts cohorts in clinical trials for ASD will be selected based on genetic subtype. "That's absolutely critical," he said.

This research better informs parents, and also provides direction on where we need to do more research, observed Anna Maria Tremonte, host of the Current. Bringing the discussion back around to the family whose story began the segment aired on her program, Tremonte asked if the findings were helpful to parents.

"We value every family in this project," said Scherer. "I guarantee that this work will help answer questions for other families, as well."