In the spring of 1846, a well-dressed man from Boston rode on horseback into a small village in Massachusetts. The man’s name was Samuel Gridley Howe, and he had set out on a special mission to create a scientific report on people who were deemed “intellectually incapacitated.” Howe ran a measuring tape around his subjects’ chests, used steel calipers to quantify the size of their skulls, and asked a great deal of questions relating to their behaviors.
Samuel Gridley Howe was gathering a large amount of data for what he thought was a report on intellectual impairment. But in reality, he was putting together the world’s earliest known collection of systematically observed people with probable autism in the United States. The final report contained 45 pages of data taken from 574 people who were meticulously examined by either Howe himself or his colleagues in almost 63 towns.
In the mid-19th century, the word “autism” did not exist, and thus, neither did the diagnosis. However, that didn’t mean the world lacked autistic minds back then. Even before Samuel Howe came on the scene, scholars had found a small number of cases with the hallmark characteristics of autism. For example, the best known case is the Wild Boy of Aveyron, a twelve year old boy who walked naked out of a forest in France in 1799. The boy was later named Victor and became a regional sensation for lacking the ability to speak and surviving the wilderness under the care of a pack of wolves. Experts now believe that Victor was born autistic.
Howe’s study demonstrated a glimmer of recognition that some of his patients did not fit the accepted definition of intellectual impairment. For example, Howe discovered many cases where a patient was considered by neighbors and friends to be intellectually disabled, yet demonstrated adequate, if not superior, cognition. He documented patients whose spoken language was severely limited, yet they had perfect musical pitch or could recall specific dates or memories with stunning clarity. If these people were alive today, they would most likely be diagnosed with autism.
Science has greatly advanced since the 1800s, and today’s scientists are now delving into the causes of autism itself. Understanding these causes could unlock better prevention efforts, more effective treatments, and even a higher level of peace for those with the condition as well as their loved ones.
Researchers have known for almost fifty years that genes contribute to autism -- based on the findings that identical twins often share the condition -- but to what extent?
With the help of multiple DNA-decoding technologies, larger sample sizes, and newer techniques, scientists have been able to delve into the human genome at faster and more precise levels than ever before. As their work has gone forward, these scientists have unburied a growing list of genetic changes that could illuminate the mystery of autism’s origins once and for all.
The bottom line is that the causes of autism are complex in the same way that the causes of cancer are complex: there are undeniably many factors that play a role in the condition. The more we dig into DNA, the hereditary material in humans, the more we discover that random environmental factors appear to play a much smaller role than once thought, and nowhere near as large as the role genes play. How large is the genetic influence? Well, keep reading to find out!
What is autism?
According to the U.S. Centers for Disease Control and Prevention (CDC), autism has become the most commonly diagnosed childhood developmental disorder, affecting 1 in every 59 children in the United States. But what exactly is autism?
Autism is a complex neurodevelopmental disorder that disrupts communicative, social, and cognitive development. It is part of a broader group of developmental disorders called autism spectrum disorders (ASDs). ASDs is an umbrella term for a variety of autism types that vary in symptoms and severity depending on the individual. These types include autistic disorder (classical autism), Asperger’s syndrome, and a general category called Pervasive Developmental Disorders (PDD).
ASDs are characterized by issues with verbal and nonverbal communication, decreased levels of social interactions, repetitive behaviors, and severely limited interests and activities. ASDs appear very early in childhood and can affect any individual, no matter their ethnic, racial, economic, or social background. However, sex seems to play a role: ASDs are four times more common in boys than in girls.
Additionally, autism is a spectrum condition. This means that some autistic people are more affected than others, and no two people with autism are exactly alike. Many autism experts claim that people with the condition all see, hear, and feel the world differently, and this affects their lives in different ways.
What are the symptoms of autism?
To reiterate, autism affects every individual differently and to varying degrees. One person could have very mild social and communicative impairments, while another could have a severe disability that requires lifelong support from their parents, school, and society.
A common, striking symptom of autism is the impairment of social interactions. Examples of this include avoiding eye contact with others, failing to respond to one’s name, and having difficulty understanding and using non-verbal social cues such as facial expressions, tone of voice, and body language. Consequently, people with autism may find it hard to understand other people’s feelings or talk about their own feelings.
Other characteristic symptoms include preferring to be alone, difficulty tolerating sensory stimuli like bright lights or loud noises, thriving on routine daily patterns, and repeating certain behaviors. Repetitive behaviors can include hand-flapping, twirling, and rocking. Some autistic individuals may display self-injurious behaviors and throw tantrums.
Many symptoms show great variation from person to person.
For example, the verbal abilities in autistic individuals can range from no speech at all to speech that is highly fluent. Additionally, affected individuals have demonstrated a wide range of intellectual abilities. Many people with autism have mild to moderate intellectual disability. However, others may have average to above-average intelligence and higher levels of functioning in areas such as mathematics, memory, or music.
How do you treat autism?
While there may not be a cure for autism, it can be managed from a young age. Studies have shown that early intensive therapy can have positive effects on a child’s development in their later stages of life. Treatment usually involves behavioral therapy to help children with their language skills and social interactions. Behavioral therapy can also be used to help children decrease their repetitive behaviors, tantrums, and self injury.
As for medications, there aren’t any that are autism specific, but certain types can help treat specific symptoms. Some doctors will prescribe medications to alleviate symptoms such as inattention, self-injurious behavior, insomnia, and even repetitive behaviors. Medications are usually used as a complement to family-centered, behavioral, and educational programs.
So, is autism genetic?
We have known for years that autism has a very strong genetic basis. But we still lack a full understanding of autism-associated genes; we are still extending the list of gene variants associated with autism and figuring out their specific interactions within the brain. Let’s put it this way, we are still searching for answers. But a lot has been discovered thus far, so we’re not searching in the dark.
What Twin and Family Studies Have Taught Us
The first autism twin studies occurred in 1977, and from these studies, we learned that autism is highly heritable. In fact, if one identical twin has autism, there is around an 80 percent chance that the other twin will have it too. The rate of probability that two people with shared genes will develop the same disease is known as the concordance rate.
The concordance rate for autism in fraternal twins is around 40 percent. Autism is considered to be one of the world’s most heritable neurodevelopmental disorders, mostly because of the large difference in concordance rates between identical and fraternal twins.
Both twin and family studies strongly suggest that some people may have a genetic predisposition to autism. For example, we now know that if a family has one child with ASD, there is an increased risk of having a second child with the disorder. The concordance rates in siblings can range from 3 percent to 14 percent. Furthermore, in some cases, a child with ASD may have relatives or parents that show mild impairments regarding social and communication skills. As you can see, autism has a tendency to run in families. Unfortunately, the inheritance pattern is still yet to be discovered.
There aren’t any “pure” autism genes, but many genes have been proven to contribute substantially to the condition. The list of genes involved in autism has been growing with no signs of stopping any time soon. So far, researchers have counted 65 genes, known as causal genes, that are considered to be strongly linked to autism. Outside of the causal genes, there are more than 200 other genes that have weaker links to the condition, but are linked nonetheless. Many of these genes produce proteins that play important roles in brain development, from the communication, organization, and function of neurons to the regulation of other genes or proteins.
Our understanding of specific ways that variations in autism-associated genes relate to autism itself is still a work in progress. However, there have been breakthroughs that shed light on our questions.
For example, previous studies have indicated that some people with autism have more neurons than normal during brain development, leading to overgrowth and abnormalities on the outer surface of the brain, or the cortex. The cortex contains specialized neurons and patterns of neural connection that are specifically involved in language, social behavior, and emotions. Thus, abnormalities in the cortex have been thought to cause the differences in communication and cognitive abilities of people with autism.
Multiple studies suggest that autism could be a result of changes, or variations, in the DNA of autism-associated genes. Some variations affect only a single DNA base, or nucleotide, pair. This genetic variant is called a single nucleotide polymorphism (SNP), and everyone has thousands of them in their body. SNPs that occur in 1% or more of the global population are considered “common”, while SNPs that occur in less than 1% of the population are considered “rare.” Scientists have found that many of the genetic variations linked to autism so far have been rare.
Some scientists have even been looking beyond single nucleotide changes to find other types of genetic variations associated with autism. For instance, recent research has shown that spontaneous gene mutations, or de novo mutations, may influence the risk of developing autism. De novo mutations are changes in DNA sequences that occur spontaneously when an egg or sperm are forming, and they may affect single genes, but usually result in changes called copy number variations, or CNVs. CNVs are when long stretches of DNA that may contain many genes are deleted or repeated, resulting in many changes across multiple genes. Studies have shown that people with autism tend to have a higher number of CNV de novo gene mutations than people without the condition. De novo mutations have been used to explain genetic disorders in which an affected child has the disorder while their parents do not and there is no family history of the disorder. Researchers are continuing to sift through the remaining genes in our genome to look for more genes associated with autism, and there is a lot more to be unearthed.
On the other hand, around 2 to 4 percent of people with autism have it as a result of other, overarching conditions caused by rare gene mutations. These conditions are associated with an increased risk for autism. They include Fragile X syndrome (causes intellectual disability), tuberous sclerosis (causes benign tumors to grow in the brain and other vital organs), Congenital Rubella Syndrome, and Phenylketonuria (PKU).
What about environmental factors?
For starters, we can’t count environmental factors out of the equation. Genetics clearly does not account for all autism risk. Although multiple studies have proven that certain environmental factors, such as vaccinations to prevent childhood infectious diseases, in fact do NOT increase the risk of autism, there is still much research to be done to determine the potential role of environmental factors that might increase that risk. Some environmental factors that are being investigated include exposure to a maternal immune response in the womb, parental age, and complications during birth. Scientists believe both genetics and the environment likely play a role in the development of autism and other ASDs.
Where do we go from here?
Currently, multiple studies have established the genetic influence on autism as being around 74 to 98 percent. However, we have yet to find the exact nature and source of that influence. If there is a genetic link to autism, it won’t be easy to find. But it also isn’t impossible. The advances in technology we’ve seen in the past few decades have allowed us to progress farther than we ever have before. We have already been able to identify 65 strong, autism-associated genes, and we’re in the process of finding more. Each discovery guides us toward the ability to understand more cases of autism.
There are numerous programs in place that are exploring autism-associated genes, recurrent CNVs, and autism-associated cellular pathways and processes of the developing human brain. The results of these programs will provide further direction for future research into potential treatments as well as earlier diagnosis of autism and other ASDs.
Autism Research by CRI Genetics
CRI Genetics is excited to announce that we are conducting our own autism study to unlock potential genetic factors involved in autism and other ASDs. We plan on releasing a comprehensive customer survey for research that will benefit our customers as well as the broader health community. (And of course, at CRI Genetics, we value our customers’ privacy, and the survey will be 100% anonymous.) Stay tuned!