Recent Studies Add Knowledge About Genetic Factors in Stuttering

By Dr. Dennis Drayna

Two recent studies have once again focused attention on the role of genetic factors in stuttering. These studies used approaches not previously applied to stuttering, and identified new genetic variants correlated with this disorder. The first study was led by Jennifer Below at Vanderbilt University Medical Center, who studied their health database, which contains over 92,000 individuals. The second, led by Shelly Jo Kraft at Wayne State University, studied an additional 16,000 individuals. The researchers on both papers collaborated extensively with each other and with researchers at the University of North Carolina, the Irish Stammering Association, and Curtin University in Perth, Australia.

A problem they faced at the outset was that very few of the individuals in the Vanderbilt database (less than 2 tenths of one percent) had a clear diagnosis of stuttering based on standard criteria. Because stuttering is much more common than this, thought to exist in roughly 5 percent of all individuals, the investigators sought to identify others in their database who likely stuttered. This estimate identified over 9,000 individuals, or about 10 percent of everyone in their database, who were classified as likely affected with stuttering. The researchers then used an approach known as a genome-wide association study (GWAS) to study genetic variants, taking advantage of pre-existing genetic typing that had been done at hundreds of thousands of specific locations in the DNA of each of these individuals. Then, they compared the genetic variants present in those with predicted stuttering with the variants in those who were not predicted to stutter. This comparison identified one variant near the CYR1A gene on chromosome 2 as significantly associated in European ancestry populations, while a second variant in the ZMAT4 gene on chromosome 8 showed a very suggestive association in African ancestry populations. How these variants might act to affect the products of these genes or cause the clinical features of stuttering remains a fascinating challenge for the future.

The second study was done by the same Vanderbilt, Curtin University, and Wayne State investigators, with additional collaborating investigators from the Irish Stammering Association and the University of North Carolina. It used stuttering cases and controls from multiple sources for a total of more than 2,000 well-studied, independently enrolled stuttering cases and 7,500 normally fluent control subjects. The same GWAS approach was used here, which found one significant association with a variant site near the SSUH2 gene. This variant appears to affect the degree to which the SSUH2 gene is turned on in muscle tissues of the esophagus. Thus, while much remains to be learned about this gene, the findings thus far point to a potentially promising connection to muscle control, a known issue in stuttering.

Jane Fraser, President of the Stuttering Foundation, commended the work saying, “The Stuttering Foundation has long been excited about genetic studies as a way to better understand the underlying causes of stuttering. We are glad to see this additional new work in the area of genetics, which will hopefully lead us to further progress.”

Dr. Drayna received his bachelor’s degree from the University of Wisconsin in 1976, and his Ph.D. from Harvard University in 1981, followed by postdoctoral training at the Howard Hughes Medical Institute at the University of Utah. He joined the NIDCD in 1997, focusing on disorders of auditory pitch perception, variation in human taste perception, and disorders of voice and speech. Dr. Drayna’s work has had a major focus on the genetics and neuroscience of stuttering.

From the Spring 2022 Magazine

CELEBRITY FOCUS

Bruce Willis

While the world knows Bruce Willis as an A-list actor, few know that he struggled with stuttering throughout his first 20 years.

Walter Bruce Willis was born in 1955 in West Germany to his German mother, Marlene, and his American GI father, David Willis. The family settled in David’s hometown of Penns Grove, New Jersey in 1957, and the couple has three other children.

Ken Venturi

As much of the nation watches the U.S. Open Golf Championship, it is impossible not to think about our late friend Ken Venturi. Ken overcame many challenges to win the Open at Congressional in 1964 and go on to become the voice of golf for more than three decades.

However, Ken faced no bigger obstacle than stuttering. Ken Venturi was a champion to those who stutter, going out of his way to share his personal experience when consulted by a colleague, friend, or child who stutters.

Lewis Carroll

The recent Disney version of Lewis Carroll’s classic, Alice in Wonderland, garnered a great deal of media hype. Even though the mainstream media has not made mention that Carroll was a person who stuttered, his family history gives credence to the discovery of the genetic link to stuttering. Carroll was born to parents who were first cousins; almost all of their eleven children, three girls and seven boys, struggled with stuttering past childhood.

Byron Pitts

Byron Pitts has brought much attention to stuttering with his memoir, Step Out on Nothing: How Faith and Family Helped Me Conquer Life’s Challenges, released in September, 2009. The book not only details his speech difficulties, but also his illiteracy until age 12 and his unstable family life. Pitts overcame the odds to become the chief national correspondent with ABC News.

Bill Withers

While Bill Withers has long been on the Stuttering Foundation's list of Famous People Who Stutter, many people probably didn’t realize he stuttered. He passed away on March 30, 2020.

Born in 1938 in Slab Fork, W.V., Withers was the youngest of six children. When his father died when Withers was small, he was raised by his mother and grandmother, both of whom worked as domestics.