What is autism?

October 19th, 2010

Every October is Autism Awareness Month in Canada. For such a complex disorder that affects millions of people, a month just doesn’t seem like enough. We asked renowned geneticist and autism researcher Professor Stephen Scherer, director of the University of Toronto’s McLaughlin Centre – which focuses on genomic medicine –  to offer perspective on this most interesting condition.

What is autism?

Autism is short for autism spectrum disorders (ASD), a group of neurodevelopmental conditions characterized by core deficits in three domains of function – namely, communication, repetitive or stereotypic behaviors and social interaction. The degree of impairment among individuals with ASD is variable, but the impact on families is universally life altering. It is important to stress that autism is not a single disorder, but really a collection of disorders that have common clinical symptoms.

I’ve heard one parent describe their child – who’s on the severe end of the spectrum – as being “stuck in the terrible twos 24/7 magnified by 100.” On the mild end is Asperger syndrome. Individuals afflicted with Asperger may only have deficits in their social interaction skills. Some people believe Albert Einstein had Asperger’s. The movie Rain Man presented the autistic savant form of autism where individuals exhibit some form of brilliance in contrast to their overall limitations. Less than one per cent of ASD sufferers fall in this group.

All these different forms of ASD – ranging from ‘severe’ to ‘high-functioning’ and everything in between, tend to be grouped together often leading to misunderstanding or misinterpretation. Communication is a vital component in proper autism diagnosis. It is also a vital aspect of how autism is portrayed to families, policy makers and the public.

How common is autism?

The latest Centre for Disease Control statistic indicates ASD affects one in every 120 children and a startling one in every 70 boys. There is much in the media about autism being on the rise. It is important to clarify that while the number of new diagnoses of autism cases is indeed increasing each year, this could represent several things including:

  • a true increase in the incidence of autism;
  • more public and medical awareness leading to more ASD diagnoses;
  • ‘shifting’ diagnoses – that is, diagnoses previously carrying another label may be re-diagnosed as ASD; and
  • all or a combination of the previously mentioned factors.

What is for sure is that ASD is not going away and while most of the existing prevalence data comes from North America and Europe studies, statistics originating from new populations seem to reveal similar numbers indicating autism has no boundaries.

What causes autism?

There is great debate in the public about what causes autism. The best scientific evidence indicates that genes – one’s DNA – are most likely the culprit in one way or another – directly or indirectly – in upwards of 80 to 90 per cent of individuals with ASD.

Some specific ASD-causing genes have now been identified. Combined these genes account for approximately 15 per cent of individuals with autism. Some of these genes include SHANK2, SHANK3, NLGN3, NLGN4, NRXN1, PTCHD1, which make proteins that control how brain cells communicate with each other.

Our work has shown that copy number variations in these specific genes and others – that is, one copy of a specific gene being present instead of the typical two – can cause ASD. There are genetic tests available for these forms of autism. With the astounding breakthroughs that are now starting to enable complete genome sequencing, we expect that we’ll soon find more ASD risk genes. I anticipate there are several hundred genes involved in ASD, and with enough investment we’ll find all of them in the next five years. My team and I have just received a grant that will allow us to sequence the genomes from 1,000 individuals with autism providing a first step towards this lofty goal.

It is important to note that birth complications and drugs like valproic acid and thalidomide seem to cause autism in a rare few – less than one per cent. Therefore, non-genetic environmental factors are also involved but we don’t yet really know to what extent. It will be important to further study how the environment causes ASD, as well as how the environment influences genetic risk factors.

How can you tell if a child has autism? Specifically, what are the warning signs and how do doctors screen for the disorder?

Lee Steele, a mother of an autistic boy, and Professor Wendy Roberts – both of our University of Toronto research team – generated a wonderful document called Autism Spectrum Disorder: Information for Parents. It is available for free at: http://www.tcag.ca/documents/Autism_Spectrum_Disorder_info_for_Parents.pdf

I highly recommend looking at this paper. The warning signs they highlight include:

  • problems with social interaction – for example, talking to, working or playing with others;
  • unusual interest in objects – that is, hyper-fixating on certain toys, appliances or machines;
  • need for sameness – a change a routine may lead to severe tantrums;
  • great variation in abilities – for example, the child may not be able to play a simple game with a friend, but will be able to understand and operate a computer;
  • not meeting language milestones or not talking at all;
  • sensory hypersensitivity – that is, strong reactions to sunlight or loud noises; and
  • repeated actions or body movements – for example, spinning, hand-flapping and walking on tippy-toes.

Children with autism might also experience difficulties with smell and distinguishing the color or texture of certain foods or clothes. Parents often comment, before their child’s diagnosis, that they thought their child was just very shy. The terms ‘trapped within ones-self’ and ‘sticky personality’ are often used.

Why does autism affect more boys than girls?

To be honest we really don’t fully know. Most studies show a 4:1 gender bias in autism, in particular when you consider the more severe forms of autism. There are many thoughts on why this is. One of the more interesting ideas suggests that through evolution males developed genes that impacted focus and survival in isolation, making it easier for them to ‘hunt and gather’ during long trips where they were isolated.

Females, on the other hand, were more involved in taking care of families. Their evolution favored different types of genes. Therefore, in today’s society a typical male is much closer to being ‘autistic’ and a slight genetic or environmental disturbance may push them across an autism threshold much easier than is the case for females.

Another explanation is that some of the genes involved in ASD are on the X-chromosome. Boys are boys because they inherit one X-chromosome from their mother and one Y-chromosome from their father. If a boy’s X-chromosome is missing a specific gene such as the X-linked PTCHD1 gene we published this year, they will be at high risk of developing ASD. Girls are different in that, even if they are missing one PTCHD1 gene, by nature they always carry a second X-chromosome, shielding them from ASD. While females are protected, autism could appear in future generations, especially in boys. The PTCHD1 story is very compelling, but this autism gene still only accounts for about one per cent of all families. In the end, I suspect there are several contributing factors. If anything is simple in autism, it’s that in autism everything is complex.

Do you believe autism can be cured?

There are new studies that show that every child who undergoes intensive behavioral intervention therapy improves in some way. In fact, I have heard rare stories of some children having full or near-full recoveries. The most important factor leading to positive outcomes, however, is to start such interventions early and in the best-case scenario even before the first signs of autism appear.

This is where our genetic discoveries will have a great impact because they will facilitate early diagnosis. We are in the process of implementing such tests in Canadian hospitals.

Unfortunately, there are not yet any effective drugs that treat autism. However, with our new gene discoveries, pharmaceutical targets are now known and companies are developing drugs for them. The progress looks very encouraging.

My dream is that there will be a pill that can help alleviate at least a few of the core deficits in autism in some individuals, and maybe all of the deficits in others. Individuals with ASD might have their own unique genetic form of autism so this might complicate coming up with a ‘magic bullet.’ We are, however, finding that autism risk genes all seem to work together in the same biochemical pathways so there may be common targets universal drugs can make an impression on.

Either way, I intend to not retire until there are more effective treatments for autism. If humans can put a man on the moon and sequence our own genomes, we can surely figure autism out. I often imagine how amazing it would be if an individual with ASD is the one who ends up finding a cure for autism!

Professor Stephen Scherer holds the GlaxoSmithKline Endowed Chair in Genetics and Genomics at The Hospital for Sick Children and the University of Toronto. Over the years, Scherer’s research group has made numerous contributions to medical genetics, including mapping, sequencing and disease gene studies of human chromosome 7. His team also contributed to discoveries of global gene copy number variation (CNV) revealing CNV to be the most abundant type of nucleotide variation of human DNA. His group also found CNV to contribute to the cause of autism.

For more information on The McLaughlin Centre, visit: http://www.mclaughlin.utoronto.ca/home.htm