Communication breakdown. The Greek orator Demosthenes was said to treat his speech impediment by talking with pebbles in his mouth and shouting above the roar of the ocean waves. US Vice President Joe Biden, brutally nicknamed Joe Impedimenta in school, worked on his stuttering reading Emerson and Yeats aloud. Hollywood actor Samuel L. Jackson overcame blocks and pauses while talking by interjecting his trade mark profanity. Given the list of famous people who stutter including Isaac Newton, Charles Darwin, and Theodore Roosevelt, I feel in pretty good company. I am a person who stutters myself, even though my speech impediment is currently mild. Stuttering is a neurodevelopmental disorder whose genetic architecture is entirely unexplored on the molecular level but clinically shares resemblance with many other neurodevelopmental disorders that we have written about on this blog. Today is International Stuttering Awareness Day. I have thought back and forth about whether I want to write this post given my personal involvement as a person who stutters and the resulting lack of objectivity. However, I finally decided to do so in order to put stuttering where it belongs – on a research blog about neurogenetics.
Stuttering. Stuttering or stammering (British English) is a fluency disorder. The usual flow of speech is interrupted by repetitions, prolongations, or abnormal stoppages. If frequent, these dysfluencies severely impact on a person’s ability to communicate. Many people who stutter develop secondary symptoms such as eye-blinking or abnormal movements that sometimes have a tic-like fashion. Not being able to “get something out” is extremely stressful and disruptive in interpersonal communication. Some people who stutter develop a deeply ingrained fear of talking in public and may develop low self-esteem, social phobia, and depression. Even though people who stutter often receive the well-meant advice that it’s not a big deal and they should simply take a breath before talking, stuttering is a disability. People who stutter face multiple stigmas that are reinforced by movies that ridicule stuttering including the role of the mad jailers in the Life of Brian or Ken in A Fish called Wanda. German-speaking readers might also recall the abominable representation of a person who stutters in Helge Schneider’s movie Texas. There is a strong male predominance to stuttering. Transient dysfluencies in children are usually distinguished from Persistent Developmental Stuttering (PDS), i.e. stuttering that began in childhood and persisted into adulthood. In most cases, stuttering is a condition that cannot be treated, but it can be managed.
The genetics of stuttering. Twin studies have demonstrated a high heritability of stuttering (>80%) and no other explanatory cause. People who stutter do not have any observable brain lesion or injury, dispelling the notion that stuttering is the result of hits on the head in childhood by an older sibling. There are also cases of stuttering after brain damage or patients who stutter as a result of as severe psychological trauma. However, the stuttering in these rare cases is different from Persistent Developmental Stuttering. Likewise, stuttering is not due to family dynamics, parental expectations, or particular character traits. With the exception of their stoppages, repetitions, and prolongations, there is nothing wrong with people who stutter. They simply have dysfluencies that occur without any cause. The fact that stuttering cannot be learned but simply appears of out nowhere has been tragically reinforced by a series of unethical experiments in the late 1930s by the American Speech Therapist Wendell Johnson.
The Monster Study. Johnson, a person who stuttered himself, wanted to investigate whether he could induce stuttering in children. His set of investigations in orphans became known as the Monster Study. Johnson and his doctoral student recruited stuttering and non-stuttering children from an orphanage in Iowa and reinforced fluent speech in the control group, while using “all the wrong things” in the intervention group, e.g. interrupting the children, making them aware of their dysfluencies, and telling them not to speak until they can get it out right. The children in the intervention group developed anxiety symptoms and became withdrawn. Stuttering became severe in the children who had stuttered prior to the beginning of the study. The children in the intervention group who spoke fluently prior to the beginning of the interventions that were aimed to produce stuttering also developed psychological problems – however, none of them became a person who stutters. Even though Johnson aimed to demonstrate that stuttering was the result of education and interaction, this unethical, despicable study that ruined the lives of several people who stuttered basically proved the opposite. Stuttering comes out of nowhere; it is idiopathic, complex genetic with a high heritability.
Imaging studies. Imaging studies in the last 20 years have managed to provide some insight into the network dysfunctions in stuttering. A breakthrough study by Sommer and collaborators in 2002 identified connectivity deficits in speech-relevant areas. In particular, the left Superior Longitudinal Fasciculus (SLF), a data highway connecting auditory and motor areas involved in speech, is thinner in people who stutter, suggesting that stuttering is the result of aberrant auditory-motor-integration. In some people who stutter like myself, speech may actually be located in the right rather than the left hemisphere, likely as a consequence of disturbed white-matter organization in the initial speech region. Stuttering happens in the brain, and it is likely a result of coordinating the sensory and motor areas involved in speech.
Stuttering genetics. Few studies have looked at the genetic basis of stuttering on the molecular level. Even though many families had been reported with PDS, linkage analysis and gene identification were elusive. Finally, in 2010, Kang and collaborators finally identified the first genes in PDS. In a large recessive Pakistani pedigree, the authors identified mutations in GNPTAB, a gene that was previously identified in mucolipidosis, a severe recessive storage disorder that is entirely unrelated to PDS. The authors went on to sequence other genes in the pathways involved including GNPTAG und NAGPA. They also identified rare variants in these genes, which were not found in controls. Even though this study has not been replicated to date, it suggests that the genetic basis of stuttering is identifiable. Future family and association studies hold the promise of finding additional genes that might help delineate possible pathogenic pathways. Of course, I am also wondering about the possible involvement of microdeletions and other neuronal pathfinding genes such as protocadherins or neurexins, given that the insufficient formation of bundle tracts may be the result of altered neuronal development.
Future directions. The genetics of stuttering remains elusive, but I have tried to make the point that technologies used in neurogenetics including linkage studies and high-throughput sequencing may easily be applied to fluency disorders where the heritability is high and genes wait to be discovered. There is increasing awareness for stuttering, also thanks to “The Kings Speech”, the 2010 Oscar-winning movie about King George V who fought against his stuttering. If this awareness of stuttering as a neurodevelopmental disorder translates into large-scale research projects, it will be exciting times ahead for stuttering genetics.