Causes of asperger’s syndrome

Autism runs in families with history of brain conditions

Family ties: Children with an autistic parent or siblings have nine times the usual odds of having autism.
Ken Wiedemann / Getty Images

Children in families with a history of brain conditions are at increased odds of being autistic, a large study in Sweden suggests1. The more closely related the family members with these conditions, the greater the child’s chances of having autism.

Other studies have reported similar trends: A child’s odds of having autism increase if she has a sibling with autism, attention deficit hyperactivity disorder (ADHD) or intellectual disability, or a parent with schizophrenia, depression, bipolar disorder or anxiety2,3,4.

The new study looked at family history of these conditions, as well as epilepsy and more than a dozen others, and included grandparents, aunts, uncles and cousins.

In autism studies, scientists tend to focus on older siblings, “but many people with autism don’t have an older sibling with autism,” says lead investigator Brian Lee, associate professor of epidemiology and biostatistics at Drexel University in Philadelphia. “Family history, in nearly every aspect of medicine, is an incredibly strong determinant of outcome.”

Lee and his colleagues examined records from 10,920 children with autism and 556,516 typical children enrolled in the Stockholm Youth Cohort, an ongoing study of children born in that city. The researchers used national registries to identify the children’s more than 8 million relatives and those relatives’ diagnoses.

Children who have a first-degree relative — a sibling or parent — with a brain condition other than autism have up to 4.7 times the usual odds of having autism, the study found. And they have up to 7.6 times the odds of having both autism and intellectual disability.

The results jibe with evidence linking risk factors for autism with those for other conditions, says James Crowley, associate professor of genetics and psychiatry at the University of North Carolina at Chapel Hill, who was not involved in the study. “Genes that predispose to one psychiatric or neurologic disorder often predispose to another,” he says.

Relative risk:

The risk of autism — with or without intellectual disability — decreases as the genetic distance between the child and the affected family member increases.

“This is really telling us that there seems to be a general liability factor, which is genetically transmitted, to having a variety of different psychiatric and neurological disorders,” says Alan Brown, professor of psychiatry and epidemiology at Columbia University, who was not involved in the study. The findings appeared in March in JAMA Network Open.

The study also found that the 8,354 children who have autism alone are more likely to have a relative with one of these conditions than are the 2,566 children who have both autism and intellectual disability.

Children with an autistic parent or sibling have 9 times the usual odds of autism and 4.1 times the odds of having autism with intellectual disability. But children who have a parent or sibling with both autism and intellectual disability have 14.2 times the usual odds of also having both conditions and 3.8 times the odds of having autism alone.

These findings support the idea that the genetics of autism with intellectual disability differs from that of autism alone, says Jakob Grove, associate professor of biomedicine at Aarhus University in Denmark, who was not involved in the study.

Lee and his colleagues are analyzing records in national registries in Denmark to look at autism’s relationship to family history of brain and other health conditions.

We thought we were just a family of eccentrics. Now we know we’ve ALL got Asperger’s…

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Autism genetics expert Ivan Iossifov breaks down recent research that sheds light on how unaffected parents can pass autism onto their child.

Parents with no history of autism in their families have a child who is diagnosed with the disorder. It’s a common and upsetting story.

A quick Google search for “autism causes” is all it takes to learn that scientists believe the disorder has a strong genetic component. So if there’s no genetic history in the family, where does a child’s autism come from?

A key fact has come to light within the last couple of years: many autism-causing genetic mutations are “spontaneous.” They occur in the affected child, but in neither parent. Mutations in this category “are not directly inherited from the parents,” explains Assistant Professor Ivan Iossifov, one of several CSHL scientists who has pioneered the study of the role of spontaneous mutations in autism causation.

“Every child has some spontaneous mutations,” explains Iossifov. “But in some unlucky children these mutations severely affect the functioning of a particular gene.”

A child’s genome is a patchwork stitched together from the genetic “cloth” contained in the mother’s egg and father’s sperm. In theory, that means that children are cut from exactly the same cloth as their parents. But in reality, there are virtually always small “factory defects” in that cloth—mutations that spontaneously arise during the sperm or egg’s creation.

Spontaneous mutations cause as much as half of all autism in situations in which only one child in the family has autism. This and other analysis comes from a study Iossifov published in 2015. He and his team looked at about 2,500 families with a single affected child and investigated the causal link to spontaneous mutations.

Professor Michael Wigler explains the genetic factors at play in his “unified theory of autism”

As Iossifov says, all of us have such mutations, and usually they have no effect at all. Humans normally have two copies of every gene, even though only one working copy typically necessary for proper functioning.

“We have two copies of most genes for a reason—it’s kind of a buffer,” says Iossifov.

This buffer protects us from spontaneous mutations in many of our genes. Iossifov and CSHL collaborator Michael Wigler theorize, however, that autism “risk genes” are particularly vulnerable to mutations. One reason is that for such genes, a person must have two working copies to function normally. As a result, a spontaneous mutation in one of these autism risk genes tends to have devastating effects.

Other major potential explanations for sporadic autism are also actively being studied, Iossifov notes, including other genetic causes and the role of factors in a child’s environment.

Read this next: What do autism “risk genes” do?

Note: For the sake of simplicity, this article uses the term ‘autism’ to refer to all autism spectrum disorders (ASDs). You can find out more about the distinction between autism and ASD here.

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Q: What are the chances of Asperger syndrome being inherited?

A: Although doctors and researchers don’t understand exactly what causes Asperger syndrome, there seems to be a strong genetic component associated with this disorder. For example, having one child in a family with Asperger syndrome significantly increases the risk of a second child in that family also having Asperger syndrome.

Asperger syndrome is a developmental disorder that affects a child’s ability to socialize and communicate effectively with others. Children with Asperger syndrome typically exhibit social awkwardness and an all-absorbing interest in specific topics.

Signs and symptoms of Asperger syndrome often include engaging in one-sided, long-winded conversations; displaying unusual nonverbal communication, such as lack of eye contact, few facial expressions, or awkward body postures and gestures; showing an intense obsession with one or two specific, narrow subjects; appearing not to understand, empathize with or be sensitive to others’ feelings; and having a hard time reading other people or understanding humor.

Doctors group Asperger syndrome with other conditions that are called autism spectrum disorders or pervasive developmental disorders. These disorders all involve problems with social skills and communication. Asperger syndrome is generally thought to be at the milder end of this spectrum.

Research has shown that a child born to parents who already have one child with an autism spectrum disorder has approximately a 4 to 10 percent chance of also developing one of these disorders, including Asperger syndrome. In families without a history of autism spectrum disorders, the chance of having a child with one of these disorders is approximately 0.7 percent.

Although there appears to be a genetic component to Asperger syndrome, it’s not the type of disorder that can be detected through genetic testing. This is because Asperger syndrome is a descriptive diagnosis. That means a child is diagnosed with Asperger syndrome based on the signs and symptoms he or she has, rather than results of a specific laboratory test.

In addition, unlike some disorders directly linked to genetics such as Down syndrome, there’s no prenatal test to show if a fetus has Asperger syndrome. And, Asperger syndrome can be difficult to diagnose in infants because many of the behaviors associated with Asperger syndrome don’t become obvious until a child nears school age or enters school.

If you have a family history of Asperger syndrome or another autism spectrum disorder and you’re pregnant or recently have had a baby, talk to your doctor about signs and symptoms to watch for in your child. In particular, children born into families who already have one child with an autism spectrum disorder need to be closely monitored and their development tracked regularly. Then if signs and symptoms of these disorders do appear, effective intervention can begin as early as possible.

If you’re concerned that your child is showing signs of Asperger syndrome, make an appointment to have your child evaluated by your pediatrician or family doctor. He or she may refer you to a developmental pediatrician, child neurologist or child psychiatrist for further evaluation. In addition, if your child is school-age, talk to school staff about assessments that are available to determine if your child is eligible for special education services.

Dr. Robert Voigt, developmental and behavioral pediatrics, Mayo Clinic, Rochester, Minn.; mayoclinic.com.

What grandmothers can teach scientists about autism’s inheritance

In the family:

Jaclyn Perry, a 20-year-old college student at the University of California, Los Angeles, has a brother with autism. Perry does not have an autism diagnosis, but she has struggled with anxiety and compulsive behaviors, including pulling out her eyebrows and eyelashes. She arranges the clothes in her closet so that each item hangs on an identical hanger, with the same amount of space between them. She has frequent panic attacks and used to obsessively check doors in her home to make sure they were locked.

Perry dismisses her mother’s idea that these quirks simply stem from the stress of growing up with a brother who has special needs. Many of the relatives on her mother’s side of the family — Perry’s grandmother and great aunts — also have anxiety, she says. “We have a lot of hard times breathing and heart palpitations and trouble sleeping,” she says. “It’s probably genetics, because a lot of people in my family have it.”

These kinds of traits may seem like random quirks in a family, but Constantino and others are betting that the mutations that underlie them also contribute to autism. So far, many of the mutations that researchers have confidently linked to autism risk were discovered precisely because they aren’t inherited: They occur spontaneously. Everyone has these so-called de novo mutations, but in people with autism, they tend to damage certain genes more frequently and severely than they do in their parents or siblings. So scientists can compare the genomes of people who have autism with those of their relatives and spot the likely culprits. “It seems to be that in families that don’t have a family history of autism, there are more likely to be these non-inherited genetic mutations,” says Jennifer Gerdts, assistant professor of psychiatry and behavioral sciences at the University of Washington in Seattle.

Family inheritance: Campbell says her son, Gregory, and his deceased father shared some autism-like traits.

Because these children with random mutations did not inherit their autism, their family members are likely to be truly ‘unaffected’ — meaning they are unlikely to have the traits that make up BAP. To confirm this impression, Gerdts is comparing these relatives with the those of people on the spectrum who have inherited mutations.

By comparison, pinning down heritable genetic variants — which are more likely candidates for BAP — has been difficult. Studying consanguineous families, in which the parents are cousins, has yielded some data. Looking at such families in the Middle East, some scientists have found children with autism who have two mutated copies of a gene, one from each parent, and identified autism risk genes.

The majority of the inherited risk for autism probably occurs via ‘common’ variants. Unlike rare de novo mutations, these variants occur in at least 1 percent of the population. Each variant may only contribute an incremental risk of autism, but inheriting a critical mass of the variants might push a person across the threshold for a diagnosis. And having less than this critical number of variants might result in BAP — enough for some quirks or behaviors to turn up, but not quite enough for a diagnosis.

So far, scientists have not been able to study anywhere near the numbers of people with autism they would need to confidently tie any particular common variant to autism. In March, a group at Harvard University reported that some common variants previously linked to autism are associated with poor social skills in children who don’t have an autism diagnosis. This finding supports the idea of a common genetic makeup for both autism and BAP. If this idea bears out, researchers may be able to learn more about autism by studying people without a diagnosis who show signs of BAP.

Because they tend to have a higher intelligence quotient and fewer secondary conditions, people without a diagnosis can be easier to study than those who do have one. This could address a persistent limitation in research. “Why only study the children who are meeting a clinical standard?” asks Angelica Ronald, reader in psychological sciences at Birkbeck, University of London. Including people with autism traits “will advance our understanding of the causes of autism faster than using the arbitrary cutoff that’s there for clinical purposes,” she says.

Expanding the study pool in this way would also allow researchers to study individual traits, such as social difficulties or restricted interests. For example, Joseph Piven has found that parents who have social difficulties have brain activity patterns that resemble those seen in people with autism. “When you don’t select out to study people who have the full syndrome of autism, like we have done forever, you basically get to study these things as they may appear independently,” says Piven, distinguished professor of psychiatry at the University of North Carolina at Chapel Hill.

Others are more circumspect, saying people who have only an autism-like trait are likely to be quite different, genetically, from those who have a diagnosis. People with autism may have distinct mutations that aren’t shared by their close relatives without autism, says Thomas Frazier, director of the Cleveland Clinic’s Center for Autism. In fact, he says, these mutations may be what draw the line between having a diagnosis and not.

WEDNESDAY, July 17, 2019 (HealthDay News) — The largest study of its kind, involving more than 2 million people across five countries, finds that autism spectrum disorders are 80% reliant on inherited genes.

That means that environmental causes are responsible for just 20% of the risk.

The findings could open new doors to research into the genetic causes of autism, which the U.S. Centers for Disease Control and Prevention now says affects 1 in every 59 U.S. children.

It might also help ease fears that autism is caused by maternal factors — a mother’s weight, mode or timing of delivery, or nutrient intake, for example. The new study found the role of maternal factors to be “nonexistent or minimal.”

Instead, “the current study results provide the strongest evidence to our knowledge to date that the majority of risk for autism spectrum disorders is from genetic factors,” said a team led by Sven Sandin, an epidemiological researcher at the Karolinska Institute in Stockholm, Sweden.

The new study might help dampen public interest in supposed — but unproven — “environmental” causes of autism, such as vaccines. Long-discredited, fraudulent data linking childhood vaccination with autism is still widely cited by the “anti-vaxxer” movement.

“The contribution of the environment to autism spectrum disorder risk appears to be much smaller than the contribution of genetics,” a team of experts said in an editorial comment on the new study, which was published July 17 in the journal JAMA Psychiatry.

However, genetic factors are frequently ignored, and instead environmental factors “often receive disproportionate attention from the public and the media, even when (as in the case of vaccine fears), they are debunked,” wrote psychiatrists Drs. Amandeep Jutla, Hannah Reed and Jeremy Veenstra-VanderWeele in the editorial. They are all from Columbia University in New York City.

According to Sandin and colleagues, the new study is the largest and most rigorous yet conducted into the causes of autism. The researchers looked at the medical histories of more than 2 million children born in Denmark, Finland, Sweden, Israel and Western Australia between 1998 and 2012. All were tracked until 16 years of age. Of the group, just over 22,000 went on to develop an autism spectrum disorder.

What Are the Causes and Risk Factors for Asperger’s Syndrome?

What Are the Possible Causes of Asperger’s Syndrome?

Many studies have looked at possible causes for autism spectrum disorders like Asperger’s. Some have provided clues that help doctors identify potential triggers.

Genes

Genes appear to affect a person’s chances of developing Asperger’s. While no one specific gene has been found to cause Asperger’s, the disorder seems to run in families. (1)

For example, younger siblings of a child with Asperger’s are at a greater risk of developing the syndrome than other kids. Studies on identical twins have shown that if one twin has an autism spectrum disorder, the other is likely to be affected between 36 and 95 percent of the time. (2)

Additionally, certain genetic conditions, such as Fragile X syndrome and Rett syndrome, are linked to the development of Asperger’s. Fragile X syndrome is the most commonly known single-gene disorder, and accounts for about 2 to 3 percent of all autism spectrum disorders. (3)

Spontaneous gene mutations, or gene changes that happen for unknown reasons, may also influence a child’s risk of developing Asperger’s.

Scientists continue to study how genes are related to Asperger’s. They hope to provide more answers to help better explain this complex connection.

Brain Changes

Imaging studies of people with autism spectrum disorders have shown differences in certain parts of the brain, especially in the areas known as the frontal and temporal lobes. (4)

Researchers are working to figure out whether these changes are due to gene abnormalities, damage during pregnancy or birth, an injury during the first few months of life, or a combination of several factors. (2)

Environment

Many experts believe environmental triggers may be a culprit for Asperger’s.

While more research needs to be done, some have theorized that certain issues during pregnancy may increase a baby’s risk of developing an autism spectrum disorder. Some possibilities include:

  • An expectant mother having a viral infection
  • Birth complications
  • In utero exposure to chemicals, such as phthalates or pesticides
  • Using certain drugs, such as Terbulin (terbutaline), Depakene (valproic acid), antipsychotics, or mood stabilizers
  • In utero exposure to air pollutants

It’s important to note that many children who are exposed to these risks never develop Asperger’s or another form of autism.

(5)

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