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Genetic Diagnosis Tied to Autism Reveals Undiagnosed Heart Condition

Emily Singer

Date Published: August 20, 2019

Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a very rare condition linked to developmental delay, hearing loss, and other issues.

Alexander was two and half years old when his parents realized there might be something wrong. His speech and motor skills lagged behind his peers, and he had trouble physically keeping up with other children his age. “He wasn’t running or jumping like other boys or drawing a typical circle,” says Megan Wise, Alexander’s mother.

A developmental pediatrician diagnosed autism. Soon after, the Wises enrolled in SPARK, the largest genetic study of autism. The family wanted to contribute to autism research. But they also hoped to better understand their son’s condition. The pediatrician suggested genetic testing, but their insurance company wouldn’t cover it. SPARK offered another route to genetic analysis.

The family knew they might not get a genetic result — about 10 percent of people who have autism and enroll in SPARK get a genetic diagnosis. In December, nearly two years after they first enrolled in SPARK, the Wises got the answer they had been looking for.

Alexander had BWCFF syndrome, a condition caused by changes in one of two different genes — ACTB or ACTG1. These genes are important for a variety of functions in cells, including the movement and division of cells as the body develops.

The condition is extremely rare. As of 2018, doctors had found about 40 people worldwide who have BWCFF syndrome. Alexander’s gene change is in the ACTB gene, which was first linked to the condition in 2006.

Alexander’s father, Daniel, was shocked when they got the diagnosis. “I think my surprise was based on me hearing and reading that no one knows what causes autism, or I guess more accurately there was no one cause,” he says. “It’s really interesting to get results that actually do explain Alex’s condition.”

ACTB is one of close to 200 genes currently linked to autism. Scientists estimate that there are hundreds more. SPARK aims to find additional autism-linked genes and to better understand the genes that are already linked to autism. This type of research could eventually help to develop new treatments for autism.

A Hidden Heart Condition

For many families, a genetic diagnosis doesn’t change their child’s non-medical treatment. Children don’t need a genetic diagnosis to get behavioral, speech, and other therapies. But BWCFF syndrome is linked to several issues in addition to autism, including hearing loss, muscle weakness, and sometimes heart and kidney issues.

Testing revealed that Alexander has a minor heart valve issue and a complication from ear tubes, both of which may require surgery. The diagnosis “helped us grab a heart defect we wouldn’t have otherwise found,” Daniel says. “We wouldn’t have gone down that path without the diagnosis.”

People who have BWCFF syndrome also have a higher risk of seizures. Alexander hasn’t had seizures yet, but his parents now know to look out for them.

As more people get diagnosed through genetic analysis, scientists are starting to better understand the condition. Researchers now know that people who have changes in the ACTB gene can show different characteristics depending on the type of change.

Some people have changes to the structure of their brain. Others have a typical looking brain but slow development and intellectual disability. Those who have autism tend to have a certain type of gene change that shortens the gene or erases a part of the gene, says Nataliya Di Donato, a physician and scientist at the Institute for Clinical Genetics in Dresden, Germany.

Di Donato says that as genetic analysis has expanded, more and more people who have changes in the ACTB gene are being diagnosed as adults. Studying this group will eventually give scientists a better picture of what families can expect as their child ages.

Alexander, who will enter kindergarten next year, loves Legos and superheroes, especially Lego batman. He enjoys running around and playing chase with his friends and his dog. “He is a pretty easygoing kid,” Daniel says. “He’s very silly, very happy, very sweet.”

He gets different types of therapy to help with speech delays and other issues. He is working on his social skills, especially in groups. That has helped him learn to communicate what he wants when he meets new people. “That was a big issue in preschool, where he couldn’t stand up for himself and say that’s my toy, or I don’t want to play that,” Daniel says. “His confidence is a lot better.”

Applied behavioral analysis (ABA) therapy, in particular, has been a huge success. “The progress has been amazing,” Daniel says. “It’s like night and day.”