When Words Fail
In the 2010 film, “The King’s Speech,” a speech therapist helps the king of England overcome a significant stutter so that he can address the nation at the outbreak of World War II.
If only it were that straightforward.
For those who stutter, and there are millions of people of all races and cultures, the inability to converse fluidly can be a lifelong challenge, even with the best available treatments. It is a life filled with fits and starts, advances and retreats, triumphs and defeats.
Beyond the repetitions, the prolongations and blocks in the flow of speech is the physical struggle — the grimaces, the averting of the eyes, the avoidance of stressful situations that might put one’s stuttering on display for all the world to stare at, tease, and even bully.
“A person who stutters may have very negative thoughts and feelings about themselves as a communicator or their ability to engage in everyday life activities,” says Robin Jones, PhD, assistant professor of Hearing and Speech Sciences at Vanderbilt University Medical Center.
“You may avoid speaking situations, opportunities or jobs,” Jones says. “A person can be at a good place, and then get a promotion and have to take on extra tasks and extra speaking pressures, and then the stuttering can get worse.”
Settling for a less stressful career choice, gingerly navigating the vagaries of everyday life in a world filled with speech — all of that can take a toll. It’s worse if, like most people who stutter, “you feel isolated and alone, like you’re the only person who has this challenge,” he says.
Jones should know. The Ohio native has stuttered for as long as he can remember. He’d had speech therapy for many years “without any remarkable change,” when as an undergraduate at Ohio’s Miami University, he encountered Paul J. Malott, PhD, an expert on stuttering.
Malott, who stuttered himself, taught Jones ways to modify how he spoke and communicated so that his speech flowed more easily, and invited him to participate in group treatment with other people who stuttered. The experience, says Jones, was “life-changing.”
“It totally changed my perception about stuttering,” he recalls. “I really became a lot more confident as a communicator … I stopped avoiding speaking situations.” Another big thing happened. Jones decided to go into speech pathology research to help other people, just as his mentor had helped him.
A pressing clinical issue
Jones went to The Ohio State University (OSU), where he completed his clinical training and earned his master’s degree in speech pathology. In 2008 he came to Vanderbilt to pursue his PhD in the Department of Hearing and Speech Sciences under Edward Conture, PhD, an internationally known expert on developmental stuttering.
Vanderbilt University Medical Center (VUMC) is home to the Vanderbilt Bill Wilkerson Center, a nationally known research, training and treatment center for children and adults with hearing loss, language and speech disorders, brain injuries and other diseases of the ear, nose, throat, head and neck.
Founded in 1951 by Nashville ear, nose and throat physician Wesley Wilkerson, MD, and named for his son Bill, who had been killed in World War II during the Battle of the Bulge, the center merged with VUMC in 1997.
Treatment provided by the center’s speech language pathologists who have expertise in stuttering can and does result in “truly remarkable and life-changing impacts on a person’s communication and overall quality of life,” Jones says.
For example, children who attend the center’s annual summer Camp TALKS (Talking And Learning with Kids who Stutter), and who are exposed to other people who stutter, including adults, often experience dramatic improvements in their communication.
“They still stutter,” Jones says, “but in some ways they have overcome it.”
After earning his PhD and completing postdoctoral work at OSU, Jones returned to Vanderbilt and joined the faculty in 2013. He resolved to provide treatments that helped his clients increase the spontaneity of their speech while mitigating the negative impact of their stuttering.
“It’s about supporting them in communicating what they want, when they want and with whom they want,” Jones says. “Broadly, it’s about helping them unlock their communication.”
But still he wondered: Why is it, that of the developmental stutterers, those who begin to stutter between the ages of 2 and 4, 75-85% eventually “grow out of it,” often without any speech therapy or treatment at all?
And for the rest, for those who continue to stutter in their later school-age years, into adolescence and adulthood, why does the vulnerability and characteristic to stutter persist — often for the rest of their lives?
The inability to distinguish children who eventually will stop stuttering from those whose stuttering will persist “is one of the most pressing clinical issues that we face currently,” Jones says.
To identify “predictors” of persistent stuttering, he and his colleagues conduct longitudinal studies of children beginning at age 3 or 4, close to the onset of developmental stuttering, and track them over time.
The goal of prediction is to provide, as early as possible, the most helpful treatments to children identified as being at risk of persistent stuttering. While the researchers have made progress in this area, “there is still room for significant improvement,” Jones said.
The genetic roots
In 2015 the ground shifted with the arrival of Nancy Cox, PhD, an internationally known expert on human genetics at the University of Chicago. Cox had done foundational work on the genetics of stuttering with Nicoline Grinager Ambrose, PhD, and Ehud Yairi, PhD, at the University of Illinois Urbana-Champaign.
Cox’s recruitment to Vanderbilt, as director of the Division of Genetic Medicine in the Department of Medicine, and founding director of the Vanderbilt Genetics Institute, burnished VUMC’s standing as a powerhouse of genetic, clinical and translational research.
A centerpiece of that research enterprise is BioVU, today the most comprehensive collection of human DNA and other biological materials stored at a single site.
DNA samples extracted from discarded blood collected at VUMC during routine clinical testing are linked to a “synthetic derivative” — a copy of electronic health records from which patients’ personal identifying information has been removed.
This linkage enables researchers to study the genetics of a wide range of health conditions, from cancer and heart disease, to now, possibly, stuttering.
About this time, Jones received an inquiry about the graduate program in Hearing and Speech Sciences from Dillon Pruett, a young man from Puyallup, Washington, about 35 miles south of Seattle.
Like Jones, Pruett had stuttered since about the time he began to string words together. Despite years of speech therapy, he continued to stutter in middle school.
Pruett endured the teasing. He wasn’t one to shrink from a challenge. In eighth grade he decided to run for student body president, even though it required that he give a speech to the entire student body.
Pruett’s speech was broadcast to classrooms throughout the school. It did not go well. “I was stuttering very severely,” he recalls. “The whole school knew. Teachers had to tell their classes that it was not appropriate to laugh.”
Pruett did not win the election. But he didn’t retreat from life, either. In high school he served as Honor Society president and Key Club vice president and was on the student council. “I didn’t want stuttering to hold me back,” he says.
In the fall of 2010, as a freshman at the University of Washington in Seattle, Pruett saw “The King’s Speech.” While he felt the movie’s portrayal of stuttering was largely accurate, he took issue with its take-home message, “that if you just try, really try, you won’t stutter.”
Still, the movie “opened the door for people to have some idea of what stuttering can look like and how it can feel,” he says. “That was helpful.”
Initially Pruett wanted to go to medical school, but within a few months he had become deeply interested in stuttering research and — in particular — the genetic aspects of stuttering.
He volunteered in the Laboratory for Speech Physiology and Motor Control directed by neuroscientist Ludo Max, PhD. Among other projects, the lab explores the neuromotor and neurophysiological mechanisms underlying stuttering.
That’s when Pruett decided to pursue a research career. “It struck me as a missed opportunity,” he says, “this chasm between the historical study of stuttering and the biosciences.”
Pruett began to look for a place that combined the two. That brought him — in the fall of 2015 — to Vanderbilt as a graduate student in Hearing and Speech Sciences.
“The integration of research and clinical care is a true strength of the Bill Wilkerson Center,” he says. “It’s been really cool to be a part of that.”
With Cox’s encouragement, in 2016 Jones and his new graduate student began to explore the potential of BioVU to plumb the genetic roots of stuttering.
But there was a problem. In the matched electronic health records, Jones and Pruett found to their surprise that the word “stuttering” could just as well describe an unusual gait, characterized by a hesitancy in taking steps, or random, unstable angina (chest pain).
Of approximately 1,800 records they reviewed that contained the keyword “stuttering,” only about 10% could be confirmed as a developmental stuttering case.
Help came in 2017 with the recruitment of Jennifer “Piper” Below, PhD, from the University of Texas Health Science Center at Houston.
Below was engaged in a major study of the genetics of stuttering with an international expert on the subject, Shelly Jo Kraft, PhD, director of the Behavior, Speech & Genetics Lab at Wayne State University in Detroit.
They’d met in 2010 at the University of Chicago, where Below was working toward her PhD in Human Genetics and Kraft was a postdoctoral scholar.
Kraft arrived at Wayne State in 2011 and, with the help of colleagues in Ireland, England, Israel, Sweden, Australia and the United States, she began collecting blood and saliva samples from people who stutter.
Over the years the researchers collected samples from more than 1,800 people who stutter, including more than 250 families with three generations of stuttering.
Called the International Stuttering Project (www.theinternationalstutteringproject.com), the effort identified new genetic variations, or variants, associated with developmental stuttering. However, it was not sufficiently “powered” to reveal the complexity of the condition. There simply were not enough people in the studies.
Below’s move to VUMC was crucial. Like Jones and Pruett, she realized the potential of BioVU to unlock the genetic mysteries of stuttering.
But because developmental stuttering is rarely mentioned or given a diagnostic code in the medical record, “we had to come up with some clever new ways to try to capture that missing code,” she says.
From confirmed cases of developmental stuttering, the researchers constructed a “constellation” of diagnostic codes for other conditions such as attention-deficit hyperactivity disorder (ADHD) and autoimmune reactions to infections that co-occur with stuttering more frequently than would be expected by chance.
Then, using machine learning techniques, they created an artificial intelligence tool that used the presence of these “phenotypes” recorded in the electronic health record to predict those who were likely to stutter, “even in the absence of having a direct note about their stuttering in their medical record,” Below says.
Supported by a $3.5 million, five-year grant awarded in 2018 by the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health, the researchers demonstrated that their stuttering prediction model positively predicted the presence of stuttering more than 80% of the time.
In two papers published in December 2021, Below, Kraft and their colleagues reported their results, what they called a “genetic architecture” for developmental stuttering, as well as the discovery of new genetic variations associated with the condition. Jones and Pruett were among the co-authors.
Among other insights, the research turned up a stuttering-related gene implicated in autism-spectrum disorder, as well as genetic variants that affect the regulation of sex hormones. The latter finding may help explain why boys are more likely to stutter, and why women who stutter are more likely to overcome it.
Tip of the iceberg
The researchers believe that studies like these have the potential to identify therapeutic directions that could improve outcomes for people who stutter.
“It’s clear that in populations, stuttering is polygenic, meaning that there are multiple different genetic factors contributing to and protecting people from risk,” says Below, associate professor of Medicine at VUMC. “That was something that had not been clearly shown before these studies.”
The papers, published in The American Journal of Human Genetics and Human Genetics and Genomics Advances, will not immediately change health outcomes for people who stutter. But they “open the floodgates for the kind of research that may one day lead to that,” she adds.
Jones believes the research may lead to breakthroughs in understanding, and potentially treating the “core, causal mechanisms” of developmental stuttering. “I think this is just the tip of the iceberg,” he says.
The new revelations also will have a huge impact on people who stutter and on the parents of children affected by the condition.
“It’s a piece of themselves that they can then understand,” Kraft says, “instead of living a lifetime of experiencing this difference in their speech and never knowing why. Why me? Why did this happen? Or for parents, why did this happen to my child?”
Adds Jones: “If we identify genes that confer a high risk for persistent stuttering, then we can provide early intervention for those children and their families. That is my hope.”
Below says the biobank study would not have been possible were it not for the case studies compiled by Kraft and her colleagues, which confirmed that the “genetic architecture we’re picking up in this large-scale biobank study actually is detecting risk factors for clinical stuttering.”
Researchers from private speech clinics in Dublin, Ireland, Curtin University in Perth, Australia, and the University of North Carolina at Chapel Hill contributed to the research. The National Stuttering Association, Irish Stammering Association and other organizations have supported the research by sponsoring collections.
Some correlations between traits may be spurious. But if the researchers establish genetic connections between stuttering and other traits such as ADHD, those findings could open avenues for treating both conditions at the same time, Kraft says.
Kraft and her colleagues are expanding their health inventories of people who stutter to capture more co-occurring conditions. “We can power these studies with electronic databases,” she says, “but we need people who stutter, who can give their individual stories and … the complexity of everything they are experiencing to validate the results.”
Jones agrees. “There’s an incredible heterogeneity of stuttering, such a wide range of experiences that people have,” he says. “It’s important to view it through the lens of the individual. A person may experience negative attitudes surrounding stuttering … like bullying (and) microaggressions.”
On the other hand, “a lot of positive things have come from my experience with stuttering,” Jones continues. “I’ve had the opportunity to meet some incredible individuals and have had profound experiences.”
Still, “communication is a quintessential aspect of the human experience,” he says. “As a person who stutters, who knows exactly what they want to say but can’t get the words out, that can have a monumental impact on an individual.
“Whatever we’re able to do to help a person say what they want to say is worth it.”