Noelle Swan

Utah Plays Key Role in Autism Genetics Research

In Healthcare on March 6, 2013 at 11:14 am

A version of this story entitled Families Dealing with Autism Navigate the Unknown was first published by ExploreUtahScience.com on January 17, 2013.

Photo Credit: Heather Cannon

Photo Credit: Heather Cannon

Heather Cannon of Murray, Utah, has three boys on the autism spectrum. Her eight-year-old son Neil started showing signs of extreme distress at just one month old. During his first Christmas, she recalls him shrieking as if in pain at the sound of family members unwrapping presents. He still has difficulty coping with sensory stimulation, becomes easily distracted and overwhelmed by loud noises, strong odors, and scratchy tags in clothing.

Today, Cannon describes Neil as “twice exceptional,” a term referring to children who are intellectually gifted and suffer from a disability. He learned the alphabet by 18 months, could differentiate between Mozart and Vivaldi at two years old, and was reading by three.

At five-years-old, Neil was officially diagnosed with Asperger Syndrome, a designation of a higher functioning autism spectrum disorder that has been used in recent decades but will be soon folded under the umbrella diagnosis of autism. By the time Neil was diagnosed, Cannon’s twin boys, Evan and Dylan, now six, were toddlers and displaying symptoms of their own. Soon, a young adult cousin confided that he also had Asperger Syndrome and Cannon began to suspect that other members of her extended family might also be on the spectrum.

As the incidence of autism spectrum disorders has skyrocketed in the past decade, researchers have turned to potentially high-risk families like Cannon’s in hopes of linking genetic factors to autism.

The Center for Disease Control and Prevention estimates that the number of children diagnosed with Autism Spectrum Disorders (ASD) has increased by 78 percent since 2007.

In Utah, the findings are even more staggering. CDC estimates indicate that ASD occurs at a rate of 1 in 47 in Utah compared to the rate of 1 in 88 seen nationwide.

Utah’s high prevalence rate, cultural emphasis on family history, and dedicated research facilities make the state an ideal place to explore autism genetics research.

Bill McMahon, Director of the University of Utah Department of Psychiatry, has studied autism in Utah for more than 25 years. He says that while he has also seen a dramatic increase in the number of children and adults presenting with autism symptoms in recent decades, he cautions that the latest Utah numbers from the CDC come from a small sample size with a broad margin of error.

He adds that some of the increase can likely be attributed to broadened diagnostic criteria, which now include a wide spectrum of disorders and an increased incentive to diagnose early with the discovery of successful early intervention treatments.

However, he suspects that genetic and environmental factors may also be contributing to the increase in prevalence.

“We are looking as hard as we can look for potential genetic and environmental factors that may contribute to it,” says McMahon, “We have collected the world’s biggest pedigrees, [lineage charts that include genetic relationships and medical histories,] with numbers of people with autism in them.”

Utah has long been a major repository for genealogical information. Members of the Church of Latter Day Saints have catalogued their family trees since the days of the Mormon pioneers. In the 1970’s a University of Utah geneticist, cardiologist, and demographer began weaving information from the LDS Church, the Salt Lake City library, and statewide death and cancer records together into the Utah Population Database (UPDB) in hopes of beginning to understand the role of genetics in cancer development.

Today the database holds records of 7 million Utahns dating back to 1904. In some cases, the family history goes back 12 generations. UPDB is participating in 160 different research projects, including suicide, inflammatory bowel disease, longevity, obesity, heart disease, and autism.

However, because autism is a relatively new diagnosis, tracing back to historical occurrences is not as simple as checking hospital records.

When one Utah mother, Carmen Pingree learned her son was autistic in the early 1980’s, she started talking with her family and just like Cannon, soon realized that autism-like symptoms had occurred several times in her father’s mother’s family line, though only her son and nephew had received a diagnosis.

She began to wonder if autism could be hereditary, but realized that the data to study that didn’t exist. “You could go back and say, ‘My aunt had cancer,’ but you couldn’t do that with autism,” Pingree said.  The family could speculate but adult members of the family had never been assessed for autism.

With cooperation from the department of social services, the special education programs in the public schools, and residential programs, Pingree tracked down 400 individuals who exhibited autism-like symptoms and were willing to submit to comprehensive testing at the university. Then she poured through family histories scrawling names on index cards and paper clipping families together.

Today, researchers are still using those pedigrees to try to identify the causes of autism. Hilary Coon, also a professor of psychiatry at the University of Utah is now working to confirm and expand them. She is matching them to data from the UPDB and hopes that having such extensive records can help identify genetic factors involved in disease.

“If you get a family that looks like it has a high occurrence of some disorder and they share DNA, then it’s possible that there is a genetic mutation that leads to susceptibility that they are sharing,” Coon said.

However, the genetics of autism promises to be complex.

While dozens of chromosomal mutations have been linked to autism, no single duplication or deletion explains all cases of a particular symptom or even manifests the same way in all individuals, Coon says. For instance, duplications in chromosomes 15 and 16 have been connected to autism, however Coon has not found any evidence of those particular mutations in the Utah pedigrees.

Hundreds of genetic factors likely contribute to autism susceptibility, and even among related individuals, there can be completely different genetic mutations causing similar symptoms, says Coon.

Coon speculates that symptoms could be the result of multiple genetic factors working together. For instance, a genetic marker appearing to indicate a predisposition might need an additional catalyst, perhaps an exposure to an illness in utero or in infancy, to produce symptoms.

Coon hopes that expanding the autism pedigrees to include medical history information gathered from the population database and additional surveys might help to reveal how risk factors influence and compound each other. Some of the questions Coon and her colleagues are asking are whether there are differences in the way neurons of autism patients’ function, if their immune response is different somehow, or if affected individuals or mothers were exposed to specific environmental events. However, answering these questions will likely take years if not decades.

That’s of little consolation to families like the Cannons dealing with autism everyday.

The biggest challenge both for families and researchers trying to understand autism seems to be that autism manifests differently in different people and can affect each individual in multiple ways.

That is certainly the case for Cannon’s three boys. Compared to Neil’s screaming and aggressive behavior, the twin’s seemed to be developing on target, she says. In time, it became clear however, that Dylan’s head banging and obsessive conversation rituals and Evan’s insatiable need for physical stimulation were also symptoms of autism.

“Our kids are impacted in so many different ways,” Cannon said. “People think of [autism] in terms of a mental issue, but it’s systemic, affecting gastrointestinal systems, vision, social skills, and behavior. Now my oldest may have Ehlers-Danlos syndrome, [a connective tissue disorder that frequently co-occurs with autism,]” Cannon said.

Autism is often associated with hampered social skills. Individuals on the autism spectrum struggle to develop social skills that others take for granted. Things like making eye contact, interpreting body language, and navigating the flow of conversation do not come intuitively to many people on the spectrum. However, individuals on the spectrum frequently suffer from a myriad of physical symptoms as well.

Nearly half of children diagnosed with autism disorders also suffer from digestive problems, which can affect behavior, ability to focus, and sleep patterns. For kids like Neil, that are extremely sensitive to touch and physical sensations, abdominal pain can lead to outbursts. Cannon says that she and her husband have learned over the years, that if Neil starts to become aggressive it’s likely because his stomach hurts.

Many individuals on the autism spectrum suffer from additional disorders, such as Ehlers-Danlos syndrome, that further complicate their symptoms and ability to function.

Another approach some scientists are taking is to develop diagnostic tests to identify disorders that seem to occur frequently among individuals on the spectrum as well as additional genetic risk factors.

Michael Paul, President and CEO of Utah-based diagnostics company Lineagen, says his company has been able to use genetic research derived from the University of Utah and other autism research facilities to help families pinpoint additional disorders that might be complicating symptoms relating to autism.

Paul says that the test is indicated for children who already have a diagnosis of autism and can be taken in the child’s doctor’s office with a simple swab inside the cheek. A partner laboratory extracts the DNA which scientists at Lineagen test with a chromosomal microarray, a silicon chip covered in millions of strands of synthetically produced DNA. The patient’s DNA bonds with those strands and attracts varying shades of fluorescent tags. A powerful laser senses those tags, which are used to construct a map of the genome. Scientists analyze these maps and interpret the results for families.

The hope is that those results can help families address symptoms better, says Lineagen senior manager Chuck Hensel. One of the first patients to receive the test turned out to have an additional disorder separate from the autism diagnosis, known as Angelman Syndrome, a neuro-genetic disorder affecting development, speech, balance, and intellectual capacity, Hensel says. The child had been participating in speech therapy for a long time, as is indicated for autistic children struggling with communication, but showed little progress, as is typical of children with Angelman Syndrome, he explained.

“Children with Angelman Syndrome rarely learn to speak,” Hensel said. “Rather than spending all that time and money for that child to be in speech therapy, the family could focus about alternative communication therapies.” Paul says that mother later called him up in tears, thanking Lineagen for changing her life.

However, not all findings are as definitive, Paul says. “We do see markers for which the clinical knowledge isn’t as well developed as others.” Genetic counselors help families to put results into this context.

Lineagen scientist Karen Ho explains that she and her colleagues monitor new genetic research constantly and inform the patients’ clinicians as studies come out that might shed light on markers identified during testing. For instance, scientists recently linked a previously unexplained chromosomal deletion to a four-fold increased risk for glaucoma. “We were able to contact those patients’ doctors and suggest that their eye health be monitored closely,” Ho said.

Paul, Hensel, and Ho all emphasize that the overall information available is still quite preliminary and Lineagen does not aim to diagnose autism. “We are not in the business of predicting, we are in the business of explaining,” Hensel said.

Other researchers and companies are working develop diagnostic tests for autism. Researchers at Children’s Hospital Boston just published a study in the journal PLOS ONE detailing a diagnostic test for autism. Study authors told Time Magazine that the test currently has an accuracy rate of 70%, but still produces too many false positives. Massachusetts-based diagnostic company SynapDx plans to begin clinical trials using the test early in 2013.

In Utah, Coon and McMahon will continue to forge ahead analyzing the Utah pedigrees. Scientists at Lineagen will look for ways to use that information to help families. Families like the Cannons will take one day at a time.

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  1. I am a 28yr. old mother of a 7yr. old son and i culodn’t even begin to understand what u or your family are going through. I don’t know anything about autistic people, but i do know a lot about unconditional love and that’s what i see when i watch this video. You and your family REALLY are the meaning of family. Not to mention the fact that even though he has autistic qualitys he’s very handson. I hope u all know that your family is a strong family.VA:F [1.9.22_1171]please wait…VA:F [1.9.22_1171](from 0 votes)

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