A Rare Syndrome, a Brother’s Love

When Zach Kon was an infant, his mother suspected something wasn’t right. He had a protruding jaw, a prominent forehead, and flattened features. As Zach grew, his speech was delayed, his facial muscle tone slackened, and when he did speak, his words were slurred and often unintelligible. Despite his exuberance toward strangers, he had aggressive outbursts at home and at school. And he constantly hugged himself. After years of misdiagnoses of Tourette syndrome or autism, DNA testing revealed that Zach had a rare disorder called Smith-Magenis syndrome (SMS), the result of a mutation in his DNA.

The family’s struggle to identify and treat Zach’s disorder inspired his older brother, Max Kon, to become a linguist and speech pathologist and devote his research to better understanding the disorder his family once called “Tourette’s Plus.”

Because SMS is not widely understood, there is no specific treatment for it, says Kon. He hopes that studying how children with SMS learn to speak and why they interpret written and spoken words differently than typically developing learners will lead to a targeted approach to treatment.

From the delayed speech and language skills to the irrepressible bonding with strangers—“He has way more friends than I do,” his brother says—Zach fits the textbook profile of SMS, a condition that affects an estimated one in 25,000 people worldwide.

The disorder is not typically inherited and is caused by a mutation, or permanent alteration, in a DNA sequence during the formation of reproductive cells in the early development of the fetus. The mutation’s cause is unknown, Kon says, and the precise genetics of SMS are for scientists in another field to decipher.

As of now, the disorder, identified in 1986 by a pair of geneticists, remains poorly understood, says Kon’s mentor, Sudha Arunachalam, a Boston University College of Health & Rehabilitation Sciences: Sargent College assistant professor of speech, language, and hearing sciences, and director of the BU Child Language Lab, where master’s student Kon (SAR’15) trained to do his research. Study sample sizes have been small, not only because the disorder is rare, but because it often goes undiagnosed.

Individuals diagnosed with SMS are often treated with applied behavior analysis (ABA), which targets skills related to attention span, language comprehension, and reading and math. (Other practitioners address SMS children’s sleep disturbances and behavior issues.) Designed for children and teens, the tasks used in ABA involve clear instructions, positive reinforcement, and repeated trials. For Zach, who wasn’t diagnosed with SMS until his teens, intervention with ABA had mixed results, Kon says. Zach’s treatment involved modifying inappropriate behavior by focusing on the “antecedent”—the conditions leading up to the behavior—rather than on the outcome. For children with SMS, “this tilts the balance toward maintaining a positive, helpful environment rather than setting expectations,” his brother says. This treatment is frequently used to treat children with autism, but tends to be less reliable for those with SMS, he says, who require more individualized intervention.

Kon has been working with Arunachalam to establish the first comprehensive picture of what the SMS population looks like in terms of language expression and understanding: their strengths and weaknesses, how their abilities grow over time, and whether this growth is dependent on the kinds of intervention they experience, she says.

Arunachalam advised Kon as he prepared the study, helping him to “formulate questions and look at the disorder from a broader research perspective,” he says. Since Kon’s graduate education has been largely focused on clinical practice as a speech pathologist, Arunachalam helped him integrate the more clinical aspects, such as language testing and behavior management, with the rigorous standards of research. She helped Kon ensure his documentation and testing met the standards of the University’s Institutional Review Board (IRB), which must approve all research involving human subjects.

Hoping to improve diagnosis of SMS

In June 2014, Kon attended a conference in St. Louis, Mo., where those with SMS and their families gathered to share experiences and learn about research and treatment updates. Kon emailed families on the participant list before the conference and recruited eight children to his study. “While autism is a more common disorder and we can recruit participants to come to the lab, SMS is far less common, so I need to go to them,” he explains. At the four-day conference, he tested the children, one-on-one, whose parents had agreed to participate.

The children, who ranged in age from 5 to 10, took part in a series of tests to probe their levels of language ability and comprehension. In one test, Kon held up a board with four pictures and asked his young participants to point to the objects—shovel, tree, hat—as he named them. While some were capable of following directions, others responded to something close, pointing, for example, to “cat” instead of “hat,” which indicates difficulty listening, hearing, or comprehending the command, says Kon. One child pointed to a dog when asked to point to a cat, indicating difficulty associating meanings and sounds. “And some children, while social and happy enough to spend time with me,” he says, “did not respond at all, indicating poor comprehension or an inability to recognize my intent.”

In another, slightly more difficult test, Kon used two pictures‚ one of a boy kicking a ball and one of a boy hugging a girl, and asked the participants to identify the picture of the boy hugging the girl. This test examines a child’s understanding of syntax. “Think of how complicated English can be,” Kon says. Sentences as similar as “The boy hugged the girl” and “The boy was hugged by the girl” require what speech pathologists call “syntactic comprehension.” “Testing this comprehension can reflect whether children show patterns in their syntax—passive versus active sentences, for example,” he says, “or whether they understand relatively complicated sentences, but can’t respond verbally with the same level of complexity. Tests like these also measure verbal memory.”

Kon hopes his work will eventually help improve diagnosis of SMS, which now is diagnosed only through genetic testing. He plans to apply to a PhD program to continue his research for the next three to four years and get a better sense of the range of abilities among those diagnosed with the disorder. He also aims to show the key differences between autism spectrum disorder and SMS, and find ways that treatment that has been effective for autism might be tailored to children with SMS. Ultimately, he hopes that his research will enable doctors to diagnose SMS more quickly and that it will lead to a targeted treatment that can be applied as consistently at home as it is at school.

“I’m still in the preliminary phase of analysis,” says Kon, who is in the process of renewing his IRB certification, which will enable him to continue collecting data to increase the sample size as well as track the same participants over time. In the meantime, the more kids with SMS Kon meets, the more he understands the challenges his brother Zach has faced.

Now 22, Zach is a high-functioning extrovert living in a group home. A fan of the Guinness Book of World Records who is emphatic about people spelling his name right, he is on medications that have largely calmed his aggression.

At the Parents and Researchers Interested in Smith-Magenis Syndrome, or PRISMS, Building Bridges of Hope Conference in 2014, Zach gave a speech to children with SMS and their families. “My family is the rock of my life and I love them dearly,” he said. “My older brother is really helpful,” and has been “right there from the start. When I am going through a rough patch he says things like, ‘Zach, calm down, take a deep breath,’ and these words will never leave my brain.”