Genetics of Stuttering
- Details
- Category: Stuttering Information
- Familial Incidence of Stuttering
- Dopaminergic Genes and Stuttering
- Lysosomal Enzyme Mutations and Stuttering
Nature vs. nurture? Many stutterers have relatives who stutter. Does this prove that family behavior patterns cause stuttering, or that stuttering is genetic?
A researcher in 1940 studied five generations of an Iowa family, with stuttering in all generations. In the third generation, three of four children in one family stuttered. The children grew up, and three moved to Kansas and lost contact with the sibling remaining in Iowa. Of the descendants of the woman remaining in Iowa, 40% stuttered. Of the descendants of the Kansas siblings, only 6% stuttered.
The researcher concluded that the Iowa family had a "tone" (parental behaviors) that was conducive to stuttering, but that the "tone" changed when family members moved to Kansas.
Twenty years later, another researcher studied the next generation. Only 2% of these children stuttered, and the researcher reported that there had been a change in the familial assumptions and attitudes about stuttering. [1]
Another speech pathologist then looked at the original study, and concluded that, "genetic transmission has been judged to provide an equally viable explanation for the data." [2]
This story proves nothing about the "nature vs. nurture" debate. All it proves is that different researchers looking at the same data can see different results, i.e., researchers usually find proof of their pre-existing beliefs.
Familial Incidence of Stuttering
At least 25 studies have investigated whether stutterers are more likely to have relatives who stutter. The general trend of these studies was that more stutterers say they have more relatives who stutter than non-stutterers say they have relatives who stutter, but the results varied so widely that they don't prove anything with certainty. It's possible that stutterers are just more aware of stuttering, i.e., I've overheard minor disfluencies in strangers that I knew were avoidances and substitutions that a non-stutterer would not have noticed. [1]
Twin studies are equally equivocal. A half-dozen studies of twins have found that concordance for stuttering (both twins either stutter or don't stutter, rather than one twin stuttering and the other not stuttering) is more likely in identical twins than in fraternal twins. But identical twins are always same sex, when fraternal twins can be opposite sex, and more males stutter than females. [3] A study of 95 pairs of identical twins reared apart found 5 stutterers (2% of the subjects, the expected prevalence). None of their twins stuttered, suggests that stuttering is not genetic. [1]
More recent research has found that when a preschool stuttering child has several family members who stuttered into adulthood, there is a greater chance that the child's stuttering will persist. If the child has family members who stuttered as children and then recovered, there is a greater chance that the child will follow this pattern. [4]
Dopaminergic Genes and Stuttering
Researchers can now study DNA directly. As any fan of the CSI: Crime Scene Investigation television series knows, DNA evidence is more reliable than older methods of investigation.
The neurotransmitter dopamine has been associated with stuttering since 1962, when the dopamine antagonist medication haloperidol (Haldol) was found to reduce stuttering. More recent studies have found that adults who stutter have elevated levels of dopamine [5], and found two other dopamine antagonist medications (risperidone or Risperdal and olanzapine or Zyprexa) that reduce stuttering.
A study of 112 Han Chinese persons who stutter associated stuttering with two dopaminergic genes (SLC6A3 and DRD2). [6] This study supported an earlier study [7] that investigated 225 persons with Tourette syndrome, their families, and controls. The study examined three genes associated with the neurotransmitter dopamine. The three genes were dopamine D2 receptor (DRD2), dopamine ß-hydroxylase (DßH), and dopamine transporter (DAT1). The three genes were associated with stuttering, Tourette's, and obsessive-compulsive disorder (OCD). This study was also supported by a study [8] that genetically associated stuttering to Specific Language Impairment, autism, and Tourette's. Stuttering, Tourette's, and OCD symptoms are exacerbated by stress, and by trying to suppress the behaviors (i.e., trying not to stutter makes stuttering worse).
However, a 2011 study questioned the association of stuttering with the dopamine D2 receptor DRD2 gene. No significant differences between stutterers and controls were observed in Brazilian and western European populations.[14]
Good Days, Bad Days, and the Anti-Stuttering Diet
Stutterers have "good days" with less stuttering and "bad days"when we can't get a word out. The "good days/bad days" syndrome may be due to varying levels of neurotransmitters. Dopamine is affected by several factors, including diet. Dopamine is produced from the amino acids phenylalanine and tyrosine. Both amino acids are components of protein. Meat sources of protein have more tyrosine than plant sources of protein. The exception is wheat germ, which is high in tyrosine. The foods highest in phenylalanine are soy and fish.
A vegetarian, wheat-free, low-protein diet should lower dopamine levels. I tried this. I stuttered less, but felt sluggish and depressed. I'd rather eat protein, feel mentally alert, and stutter.
The Edge Effect: Achieve Total Health and Longevity with the Balanced Brain Advantage, by psychiatrist Eric Braverman, discusses the four neurotransmitters (dopamine, acetylcholine, GABA, and serotonin) and suggests that health and well-being relates to balancing the four via diet, supplements, and/or medication. The book includes a questionnaire that shows which of your neurotransmitters are higher or lower and if any are out of normal range. You can do the questionnaire free on the Los Gatos Longevity Institute website.
My score indicated that my neurotransmitters were within normal range. But if your score shows high dopamine, than maybe diet, supplements, and/or medications are something you should look into. If you do the questionnaire, e-mail me the results. It'll be interesting to see if stutterers have on average high or low dopamine levels.
Linkage Studies
A study of 46 Pakistani families including 144 stutterers suggested "that a locus on chromosome 12q may contain a gene with a large effect in this sample." [13]
A study of 100 families of European descent in the United States, Sweden, and Israel, with 252 stutterers, found "moderate evidence for linkage" on chromosomes 9 and 15. A higher level of significance was found for male stutterers on chromosome 7 and for female stutterers on chromosome 21, suggesting that "the genetic component to stuttering has significant sex effects." [12]
Lysosomal Enzyme Mutations and Stuttering
Another genetic study investigated a family in Pakistan in which 44 of the 82 family members stuttered. This family particularly interested genetic researchers because the family was inbred: three siblings of one family married three siblings who were their parents' first cousins; three sons and three daughters of these three couples then married each other. Such inbreeding amplifies genetic mutations. The researchers called them the PKST72 family.
An initial study [9] looked for linkages or inherited genes. Such genes were found on chromosomes 1, 5, 7, and 12 with the strongest linkages on chromosome 12. The dopaminergic genes associated with stuttering in previous studies are on chromosome 11 (DRD2 and D H) and chromosome 5 (DAT1 and SLC6A3). This family apparently has nothing abnormal about their dopaminergic genes on chromosome 11. Whether they have anything abnormal about their dopaminergic genes on chromosome 5 wasn't investigated.
A second study [10] focused on chromosome 12, but expanded the field of the study to include 123 unrelated Pakistani stutterers, 96 Pakistani non-stutterers, 270 American and British stutterers, and 276 American and British non-stutterers. The second study found a mutation in the PKST72 family. 52 of the 82 PKST72 family members have a mutation called G3598A in the GNPTAB gene. 41 of the 44 stutterers in the PKST72 family had the mutation. 11 of the 38 non-stutterers in the family had the mutation.
Outside the PKST72 family, 8 of the 123 unrelated Pakistani stutterers had this mutation; 1 of the 96 Pakistani non-stutterers had this mutation; 2 of the 270 American and British stutterers had this mutation (one of whom was of South Asian descent); and none of the 276 American and British non-stutterers had this mutation.
Nine other mutations on three genes (GNPTAB, GNPTG, NAGPA) were found. One mutation was found in four of the 393 stutterers (1%). Another mutation was found in ten stutterers but eight of these stutterers were Pakistani, i.e., less than 1% of the non-Pakistani stutterers had the mutation. The other mutations were found in only one or two persons who stutter (out of 393). One non-stutterer was found to have one of these mutations.
Other mutations in GNPTAB and GNPTG have been associated with the rare inherited lysosomal storage disorders mucolipidosis types II and III, which are characterized by disorders of the joints, skeletal system, heart, liver, spleen, and motor systems and by developmental delay. Lysosomes are the waste disposal system in animal cells, using acid hydrolase enzymes to break up waste materials and cellular debris. [11] Stuttering isn't a lysosomal enzyme disorder. None of the subjects examined had mucolipidosis. The third gene in which mutations were found, NAGPA, has not been associated with any disease.
The researchers concluded that their "results can explain only a small fraction of cases of stuttering."
References
[1] Bloodstein, O. & Bernstein Ratner, N. A Handbook on Stuttering (2007; ISBN 978-1-4180-4203-5).
[2] Wingate, M. (1986) "Physiological and genetic factors." In G.H. Shames & H. Rubin, Eds.), Stuttering Then and Now (pp.49-69). Columbus: Charles E. Merrill Publishing Co.
[3] Yairi, E. Ambrose, N., & Cox, N. (1996) "Genetics of Stuttering: A Critical Review," Journal of Speech and Hearing Research, 39, 771-784.
[4] Yairi, E., & Ambrose, N.G. Early Childhood Stuttering for Clinicians by Clinicians. (2005, ISBN 89079-985-7), page 309.
[5] Bloodstein, O. & Bernstein Ratner, N. A Handbook on Stuttering (2007; ISBN 978-1-4180-4203-5), page 377, referencing Wu, Maguire (1997).
[6] Jie Lan, Manshu Song, Chunhui Pan, Guoqing Zhuang, Youxin Wang, Wenzhan Ma, Qiaoyun Chu, Qingxuan Lai, Feng Xu, Yanli Li, Lixin Liu & Wei Wang. (2009). Association between dopaminergic genes (SLC6A3 and DRD2) and stuttering among Han Chinese. Journal of Human Genetics 54, 457-460 (August 2009), doi:10.1038/jhg.2009.60.
[7] Comings, David E., S. Wu, Connie Chiu, Robert H. Ring, Radhika Gade, Chul Ahn, James P. MacMurray, George Dietz & Donn Muhleman. (1996). Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: The additive and subtractive effect of the three dopaminergic genes DRD2, D H, and DAT1. American Journal of Medical Genetics 67:3, 264-288. DOI: 10.1002/(SICI)1096-8628(19960531)
[8] Wittke-Thompson, J.K., Ambrose, N., Yairi, E., Roe, C. Cook, E., Ober, C., & Cox, N.J. (2007). Genetic studies of stuttering in a founder population. Journal of Fluency Disorders, 32, 33-50.
[9] Naveeda Riaz, Stacy Steinberg, Jamil Ahmad, Anna Pluzhnikov, Sheikh Riazuddin, Nancy J. Cox & Dennis Drayna. (2005). Genomewide Significant Linkage to Stuttering on Chromosome 12. American Journal of Human Genetics, 76:4, 647-651, 1 April 2005 doi:10.1086/429226
[10] Changsoo Kang, Sheikh Riazuddin, Jennifer Mundorff, Donna Krasnewich, Penelope Friedman, James C. Mullikin, and Dennis Drayna. (2010). Mutations in the Lysosomal Enzyme Targeting Pathway and Persistent Stuttering. New England Journal of Medicine 362:8, February 25, 2010.
[11] "Lysosome," Wikipedia, accessed 2011 March 19.
[12] Suresh R, Ambrose N, Roe C, et al. New complexities in the genetics of stuttering: significant sex-specific linkage signals. Am J Hum Genet 2006;78:554-63. PMCID: PMC1424690
[13] Shugart YY, Mundorff J, Kilshaw J, et al. Results of a genome-side linkage scan for stuttering. Am J Med Genet A 2004; 124A:133-5. PMCID: PMC1199301. Riaz N, Steinberg S, Ahmad J, et al. Genomewide significant linkage to stuttering on chromosome 12. Am J Hum Genet 2005;76:647-51
[14]Changsoo Kang, Bianca Santos Domingues, Eduardo Sainz, Carlos Eduardo Frigerio Domingue2, Dennis Drayna1, and Danilo Moretti-Ferreira. (2011) Evaluation of the association between polymorphisms at the DRD2 locus and stuttering. Journal of Human Genetics advance online publication, 10 March 2011; doi:10.1038/jhg.2011.29
