A Genetic Basis for Stuttering

A new study that identifies genetic links to stuttering may go a long way towards dampening the associated stigma.

On March 9, 2024, at a campaign stop in Rome, Georgia, the current President of the United States ridiculed the former President for stuttering while delivering the State of the Union address.

“I’m gonna bring the country tuh-tuh-tuh-together,” uttered the always uncouth #47.

Sadly, he isn’t alone in making fun of difficulty speaking.

Stuttering in Popular Culture

The entertainment industry has long incorporated stuttering into TV, film, and song: MASH, My Cousin Vinny, Star Wars: The Last Jedi, The King’s Speech, One Flew Over the Cuckoo’s Nest, South Park, and David Bowie’s Changes.

Wikipedia relates the tale of cartoon character Porky Pig, who was originally voiced by a man who stuttered, and was replaced by Mel Blanc, who faked the stutter. After pushback from the National Stuttering Project and the Stuttering Foundation of America, Warner Brothers transformed Porky Pig into an advocate for children who stuttered. The beloved pig eventually uttered, in a PSA, “Everyone’s unique and th-th-that’s good, folks!”

“A Clinical Study of Porky Pig Cartoons,” a more scientific approach, points out that Porky, from Looney Tunes/Merrie Melodies and around since 1935, “stutters on approximately 23% of his spoken words and has a wide variety of stuttering symptoms,” writes Gerald F. Johnson, from the Center for Communication Sciences and Disorders at the University of Wisconsin-Stevens, adding that Porky’s father also stuttered. Yet “in spite of negative opinions about this stuttering pig, these cartoons might be beneficial in therapy with children who stutter,” he concludes.

Definition and Description

Stuttering is the repetition of syllables and words, prolongations of sounds, and breaks between words. It is the most common fluency disorder, and affects more than 400 million people worldwide and more than 3 million in the US, according to the American Speech-Language-Hearing Association.

It typically begins in children between ages 2 and 5. About 80% of them outgrow it, whether or not they have speech therapy. In very young children, girls and boys are about equally affected, but the trait persists in four times as many males as females. That is, more girls spontaneously cease stuttering.

The trait can profoundly affect a person’s day-to-day life, due to the reactions and prejudices of others.

Three months after the President’s mocking of Joe Biden, the Journal of Fluency Disorders published a study from Michael P. Boyle and Madeline R. Cheyne of the Department of Communication Sciences and Disorders at Montclair State University, “Major discrimination due to stuttering and its association with quality of life.” They polled 303 people who stutter about how the trait has affected their day-to-day lives. Not surprisingly, their findings confirmed that those who have difficulty getting words out are the targets of ridicule, discrimination, and stereotyping.

But asking people who stutter to describe their experiences is science light – both observational and confirming what we already know, perhaps providing novel examples of difficult-to-pronounce words. Discovery of genetic underpinnings of the trait of stuttering might lend it a certain gravitas that might diminish the negative actions of others. Just such an investigation has come from an unexpected source.

23andMe Provides a Treasure Trove of Data to Explain Stuttering

A team from the Vanderbilt Genetics Institute has put a science-based stamp on stuttering, with findings just published in Nature Genetics. The researchers analyzed the massive data stream from the former consumer genetic testing company 23andMe to identify areas of the human genome sequence that harbor gene variants that people who stutter uniquely share. That is, not “a gene” for stuttering, but rather several genes with variants that, in combination, interfere with speech in this characteristic way.

Yes, that 23andMe, the company whose kits once festooned the shelves at Walgreen’s and responsible for sudden new families (like mine). The company slowly faded away due to the ultimate obsolescence of the business design –no repeat customers.

After a brief association with biotech company Regeneron in May, 23andMe’s data dump has landed at the TTAM Research Institute, “a nonprofit public benefit corporation based in California and founded and led by Anne Wojcicki”- co-founder of 23andMe. The institute acquired the Personal Genome Service and Research Services business of the company.

I deleted my 23andme data due to paranoia stemming from the current administration (that’s why I never use the president’s name). Now I feel a little badly, because the new Nature Genetics findings indicate how the company’s data are still being used to discover more about ourselves. The stuttering study reflects input from more than a million people who spit into tubes and sent in their DNA.

The Stigma of Stuttering

Identifying sets of gene variants that people who stutter uniquely share can provide guideposts to identifying neural pathways for speech that are disrupted. And that might suggest new approaches for therapies. Illuminating shared genetics might also lessen the stigma, perhaps transforming views of the condition to a neurological variant rather than reflecting a person’s intelligence.

“No one really understands why someone stutters; it has been a complete mystery. And that’s true for most speech and language pathologies. They are profoundly understudied because they don’t put people in the hospital, but they can have enormous consequences on people’s quality of life. We need to understand risk factors for speech and language traits so that we can identify kids early and get appropriate care for those that want it,” said Jennifer Below, director of the Vanderbilt Genetics Institute.

She pointed out that young people who stutter report bullying, and in response they tend to remain quiet in school. Stuttering can also negatively impact employment opportunities and perceived job performance, as well as mental and social well-being, she noted.

“There have been hundreds of years of misconceptions about what causes stuttering — from ideas about left-handedness to childhood trauma to overbearing mothers,” Below said. “Rather than being caused by personal or familial failings or intelligence, our study shows that stuttering is influenced by our genes.” She and coauthor Shelly Jo Kraft, from Wayne State University, have been exploring the genetics of stuttering for more than two decades.

The International Stuttering Project sent the researchers blood and saliva samples from more than 1,800 people who stutter. But that wasn’t a large enough number to support a genome-wide association study (GWAS), a standard genetic tool that scans a million or more genomes to identify shared DNA sequences.

And that’s where 23andMe came in.

A customer is offered quizzes on a regular basis, so that the company’s algorithms could look for patterns – that is, DNA sequences that people with a certain trait uniquely share. Some seemed silly to me – can you carry a tune? Are you a night person or a day person? Food preferences. Exercise habits. Appearance. Mood. If you keep clicking away for more, you could have answered 1273 questions.

The constant questions caught the attention of Below. “A friend sent me a picture of the 23andMe survey questions, and one was ‘Have you ever had a stutter or stammer?’ I thought, oh my gosh, if we can get access to this case-control information, it will be game-changing.”

The company agreed to share the data and formed a collaborative partnership with the researchers, who analyzed the responses of 99,776 participants who answered “yes” to the stutter or stammer question, and 1,023,243 controls who answered “no.”

We geneticists are notoriously bad at naming new tools and technologies – GWAS is among the worst, difficult to say and remember. The 23andMe GWAS hunted for places in the genome where the DNA base – A, T, C, or G – varies in a specific, typically huge, population. Sets of uncommon DNA bases in the sequence can reveal genetic underpinnings of traits if they’re only (or mostly) seen among people with the trait.

Fortunately, researchers condense unwieldy GWAS data into polygenic risk scores, aka a PRS.

The team discovered 57 distinct sites in the genome, which correspond to 48 genes, associated with stuttering risk. Males were more likely to report stuttering than females, but that could be because girls are more likely to age out of the trait as they reach their teens.

One gene, VRK2, stood out for association with stuttering in males. The gene is also associated with beat synchronization (self-reported ability to clap to a beat) and with language decline in people with Alzheimer’s disease. So what could that mean?

“Historically, we’ve thought of musicality, speech, and language as three separate entities, but these studies suggest there might be a shared genetic underpinning — that the architecture of the brain that controls our musicality, our speech and our language might be all part of a shared pathway,” Below said. “To begin to understand at a biochemical, molecular, cellular level what makes us who we are as a species — our capacity for communication — is incredibly cool, and we hope this will spur additional studies of this gene and its function in the brain.”

Co-author Dillon Pruett stutters. “As someone personally affected, I wanted to contribute to this body of research. Our study found that there are many genes that ultimately contribute to stuttering risk, and we hope to use this knowledge to dispel stigma related to stuttering and also to hopefully develop new therapeutic approaches.”

I hope that the President doesn’t cut funding for this study because it is deemed too “woke” or entails actual science.