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Discover SPARK

A Genetic Diagnosis Surprises an Ohio Family

Marina Sarris

Date Published: January 2, 2020

Jessica McGregor felt nervous when she read an email from SPARK saying it had found the cause of her son’s autism.

She, husband Shawn, and son Jensynn gave DNA samples to the SPARK study a year earlier. But they did not expect SPARK to find anything. After all, no one had ever suggested genetic testing for Jensynn, a talkative boy who loves science, animals, and insects.

Jessica McGregor knew that some changes to genes could increase the risk of serious medical problems. Would that be the case for Jensynn?

She pushed aside that fear and scheduled a call with a genetic counselor provided by SPARK. The counselor explained that Jensynn has a rare change to his SMARCC2 gene, specifically a deletion in the gene that he did not inherit from his parents. This kind of change is called “de novo,” a Latin term meaning new.

After speaking with the genetic counselor, McGregor felt more at ease. “I like the way SPARK gives you the information. They make it so it’s not overwhelming, and it’s easy to understand.” And as she learned about SMARCC2, she says, some of Jensynn’s motor and sensory difficulties made more sense.

Spinning Wheels

Before Jensynn’s first birthday, his mother noticed he had unusual habits. Jensynn would spin the wheels on his toys and stare at them intently. And “speech was not happening,” McGregor says. He began walking at 14 months and struggled with balance and coordination. She shared her concerns with his doctor, who took a “wait and see” approach.

The family moved temporarily from Ohio to Tennessee to help a relative. There, Jensynn saw a specialist who diagnosed him with autism spectrum disorder (ASD) when he was 2. “I was expecting it, but still it was kind of a shock,” McGregor says.

Jensynn received speech, occupational, and physical therapies for speech and motor delays. He also enrolled in a preschool for children who have developmental delays.

The family moved back to Ohio when Jensynn was getting ready for kindergarten. Now age 8, Jensynn receives some special education services as part of his Individualized Education Program at school. “Jensynn has amazing speech,” his mother says. He recently asked his father a question. When his dad answered, Jensynn replied, “Thank you for submitting your answer.”

He enjoys science, especially learning about dinosaurs, the solar system and dwarf planets, animals, and insects. Jensynn says his favorite insect is a wasp. He also likes to visit pet stores and play with the cats, ferrets, and puppies there.

He has a great sense of direction, memorizing how to get to places he has only visited once. “That’s surprising to me because when I was a kid and my parents would drive somewhere, I wouldn’t pay any attention to the route,” his mother says.

Although he has many strengths, he faces some challenges, too. He is very sensitive to touch, especially involving his mouth, which is called oral aversion. He cannot tolerate certain foods or having dental work. He once had to have anesthesia to have dental work performed. That experience alarmed McGregor, because it took him longer than is typical to wake up from the anesthesia.

Many people who have autism have unusual reactions to their senses of touch, smell, hearing, sight, or taste.

Jensynn sometimes experiences stomach pain after eating, and he seems sensitive or allergic to some foods, she says. Reports of gastrointestinal problems in children with ASD range from 9 to 70 percent, with autism clinics reporting the higher amount.1

Jensynn also struggles to communicate his feelings when he’s upset, and to calm himself down. Certain foods seem to cause or worsen problems with managing anger, so they avoid those foods, she says.

Are some of these issues explained by SMARCC2-related syndrome?

Joining Research, Getting Results

The McGregors joined SPARK, the largest study of autism, in 2018, after learning about it from a Facebook group. SPARK conducts genetic analyses of participants to look for changes in genes and in segments of chromosomes where there may be missing or extra material. Chromosomes are the structures in cells that contain genes. By such methods, scientists from SPARK and other research projects are identifying more and more genes that are linked to autism.

In January 2019, a scientific journal published a paper describing a syndrome caused by changes to the SMARCC2 gene. An international group of researchers studied 15 children and teenagers who have different changes to that gene.2 All 15 have intellectual disability or developmental delays ranging from mild to severe. Thirteen have speech delays, with seven having no language. Thirteen have low muscle tone, eight have feeding problems, four have seizures, and two have heart abnormalities.2

Two-thirds of the group have behavioral symptoms, such as hyperactivity, aggressiveness, obsessive and rigid behavior, and being very sensitive to touch. Two have problems with social interactions but do not have an autism diagnosis.2

Some of the symptoms found in the 15 people, such as being sensitive to touch, rigid behavior, and speech delays, are also found in autism. A change to SMARCC2 raises the risk of autism, says a leader of the research team, Philippe M. Campeau, M.D., of the CHU Sainte-Justine Research Center and University of Montreal.

Some of the 15 youth have similar physical traits, such as thick eyebrows, an upturned nose, a thin upper or thick lower lip, or extra body hair.

Jensynn does not have those physical traits, his mother says. Nor does he have the feeding and growth problems sometimes found in SMARCC2 syndrome.

In fact, unlike many third graders, he eats a variety of fruits and vegetables. While McGregor was chopping vegetables recently, Jensynn asked her if he could taste both raw green peppers and onions. To her surprise, he liked both. “My mind was just blown,” she says.

Little is known about the newly described SMARCC2-related syndrome. The McGregors have questions that they hope will be answered when more research is done. For example, Shawn McGregor asks, “How many adults have SMARCC2 changes?”

Campeau, who has been researching SMARCC2 and related genes, says that SMARCC2-related syndrome is very rare. “There will be an increase in awareness of the condition now that we published about it,” he says. He predicts that about 50 people will be diagnosed with a significant change to a SMARCC2 gene in the next three years.

To contribute to research into that gene, the McGregors joined Simons Searchlight, which studies rare genetic conditions. “Simons Searchlight is the next step in research for SPARK families who receive a genetic diagnosis,” explains Jennifer Tjernagel, senior project manager of Searchlight. “Once we know the genetic diagnosis, there are many other questions to ask, and Searchlight takes a deeper dive into getting those answers with families.” SPARK and Searchlight are both funded by the Simons Foundation Autism Research Initiative.

Looking Ahead for Jensynn

Although she felt apprehensive when she first heard about SMARCC2, Jessica McGregor says she is glad to have that information. She shared the news with Jensynn’s doctor, who is interested in genetics. “The doctor said to wait and see what other information comes out about it, and not jump to conclusions or be scared,” she says. The McGregors hope further research will help prepare people who have SMARCC2 changes for health challenges that could arise in the future.

She encourages other families to join SPARK. “We can be affecting our children’s outcomes later in life by learning about [gene changes],” she says. “We all want to find ways to help our children succeed and have the best chance for a happy, healthy life.”

References

  1. Buie T. et al. Pediatrics 125, Suppl. 1:S1-18 (2010) PubMed
  2. Machol K. et al. Am. J. Hum. Genet. 104, 164-178 (2019) PubMed