Genetic Bases of Stuttering: The State of the Art, 2011Kraft S.J.a · Yairi E.b, c
aWayne State University, Detroit, Mich., and bUniversity of Illinois at Urbana-Champaign, Urbana, Ill., USA; cTel Aviv University, Tel Aviv, Israel
Shelly Jo Kraft
Communication Sciences and Disorders
Wayne State University
60 Farnsworth Street, Detroit, MI 48202 (USA)
Tel. +1 313 577 3339, E-Mail firstname.lastname@example.org
Do you have an account?
Objective: The literature on the genetics of stuttering is reviewed with special reference to the historical development from psychosocial explanations leading up to current biological research of gene identification. Summary: A gradual progression has been made from the early crude methods of counting percentages of stuttering probands who have relatives who stutter to recent studies using entire genomes of DNA collected from each participant. Despite the shortcomings of some early studies, investigators have accumulated a substantial body of data showing a large presence of familial stuttering. This encouraged more refined research in the form of twin studies. Concordance rates among twins were sufficiently high to lend additional support to the genetic perspective of stuttering. More sophisticated aggregation studies and segregation analyses followed, producing data that matched recognized genetic models, providing the final ‘go ahead’ to proceed from the behavior/statistical genetics into the sphere of biological genetics. Recent linkage and association studies have begun to reveal contributing genes to the disorder. Conclusion: No definitive findings have been made regarding which transmission model, chromosomes, genes, or sex factors are involved in the expression of stuttering in the population at large. Future research and clinical implications are discussed.
© 2011 S. Karger AG, Basel
- Henry D: Aristotle on the mechanisms of inheritance. J Hist Biol 2006;39:425–455.
- Mendel G: Versuche über Pflanzen-Hybriden. J Hered 1951;42:3–47.
Ross MA, Hon LD: The Works of Aristotle. Oxford, Cambridge University Press, 1927.
Schaffer EJ: Part of our heritage. ASHA 1966;167–168.
Bloodstein O, Bernstein-Ratner N: A Handbook on Stuttering, ed 6. New York, Thomson-Delmar, 2008.
Johnson W: A study of the onset and development of stuttering. J Speech Hear Disord 1942;7:251–257.
Johnson W, et al: The Onset of Stuttering. Minneapolis, University of Minnesota Press, 1959.
- Andrews G, Morris-Yates A, Howie P, Martin N: Genetic factors in stuttering confirmed. Arch Gen Psychiatry 1991;48:1034–1035.
- Felsenfeldt S: Progress and needs in the genetics of stuttering. J Fluency Disord 1996;21:77–103.
- Yairi E, Ambrose N, Cox N: Genetics of stuttering: a critical review. J Speech Hear Res 1996;39:771.
Yairi E, Ambrose N: Early Childhood Stuttering. Austin, Pro-Ed, 2005.
Bryngelson B, Rutherford B: A comparative study of laterality of stutterers and non-stutterers. J Speech Hear Disord 1937;2:15–16.
Wepman JM: Familial incidence of stammering. J Hered 1939;30:207.
- Ambrose NG, Yairi E, Cox N: Genetic aspects of early childhood stuttering. J Speech Hear Res 1993;36:701–706.
Kidd K: Stuttering as a genetic disorder; in Curlee R, Perkins W (eds): Nature and Treatment of Stuttering. San Diego, College Hill, 1984, pp 149–169.
- Bulik CM, Sullivan PF, Tozzi F, Furberg H, Lichtenstein P, Pedersen NL: Prevalence, heritability, and prospective risk factors for anorexia nervosa. Arch Gen Psychiatry 2006;63:305–312.
- Greenberg DA, Hodge SE, Sowinski J, Nicoll D: Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Gen 2001;69:1062–1067.
Berry MF: Twinning in stuttering families. Hum Biol 1937;9:329–346.
Berry MF: A common denominator in twinning and stuttering. J Speech Hear Disord 1938;3:51–57.
Nelson SF, Hunter N, Walter M: Stuttering in twin types. J Speech Hear Disord 1945;10:335–343.
Graf OI: Incidence of stuttering among twins; in Johnson W, Leutenegger R (eds): Stuttering in Children and Adults. Minneapolis, University of Minnesota Press, 1955, pp 381–386.
- Godai U, Tatarelli R, Bonanni G: Stuttering and tics in twins. Acta Genet Med Gemellol (Roma) 1976;25:369–375.
- Howie PM: Concordance for stuttering in monozygotic and dizygotic twin pairs. J Speech Hear Res 1981;24:317–321.
- Howie PM: Intrapair similarity in frequency of disfluency in monozygotic and dizygotic twin pairs containing stutterers. Behav Genet 1981;11:227–238.
- Felsenfeld S, Kirk KM, Zhu G, Statham DJ, Neale MC, Martin NG: A study of the genetic and environmental etiology of stuttering in a selected twin sample. Behav Genet 2000;30:359–366.
- Ooki S: Genetic and environmental influences on stuttering and tics in Japanese children. Twin Res Hum Genet 2005;8:69–75.
- Dworzynski K, Remington A, Rijsdijk F, Howell P, Plomin R: Genetic etiology in cases of recovered and persistent stuttering in an unselected longitudinal sample of young twins. Am J Speech Lang Pathol 2007;16:169–178.
- van Beijsterveldt CEM, Felsenfeld S, Boomsma DI: Bivariate genetic analysis of stuttering and nonfluency in a large sample of 5-year-old twins. J Speech Lang Hear Res 2010;53:609–619.
- Suarez BK, Cox NJ: Linkage analysis for psychiatric disorders. I: Basic concepts. Psychiatr Dev 1985;3:219–243.
Kay D: The genetics of stuttering; in Andrews G, Harris M (eds): The Syndrome of Stuttering. London, The Spastic Society Medical Education and Information Unit, 1964, pp 132–143.
Andrews G, Harris M: The Syndrome of Stuttering. Clinics Dev Med. London, Spastics Society Medical Education, 1964, No 17.
- Mansson H: Childhood stuttering: incidence and development. J Fluency Disord 2000;25:47–57.
- Kidd KK: A genetic perspective on stuttering. J Fluency Disord 1977;2:259–269.
- Kidd KK: Genetic models of stuttering. J Fluency Disord 1980;5:187–201.
- Kidd K, Heimbuch R, Records M: Vertical transmission of susceptibility to stuttering with sex-modified expression. Proc Natl Acad Sci USA 1981;78:606–610.
- Kidd KK, Kidd JR, Records MA: The possible causes of the sex ratio in stuttering and its implications. J Fluency Disord 1978;3:13–23.
Kidd K, Reich T, Kessler S: A genetic analysis of stuttering suggesting a single major locus. Genetics 1973;74(part 2):S137.
- Kidd KK, Heimbuch RC, Records MA, Oehlert G, Webster RL: Familial stuttering patterns are not related to one measure of severity. J Speech Hear Res 1980;23:539–545.
- Cox NJ, Kidd KK: Can recovery from stuttering be considered a genetically milder subtype of stuttering? Behav Genet 1983;13:129–139.
- Cox NJ, Kramer PL, Kidd KK, Rao DC: Segregation analyses of stuttering. Genet Epidemiol 1984;1:245–253.
- Seery CH, Watkins RV, Mangelsdorf SC, Shigeto A: Subtyping stuttering. II: Contributions from language and temperament. J Fluency Disord 2007;32:197–217.
- Yairi E: Subtyping stuttering I: a review. J Fluency Disord 2007;32:165–196.
- Janssen P, Kloth S, Kraaimaat F, Brutten G: Genetic factors in stuttering: a replication of Ambrose, Yairi, and Cox’s 1993 study with adult probands. J Fluency Disord 1996;21:105–108.
- Poulos MG, Webster WG: Family history as a basis for subgrouping people who stutter. J Speech Hear Res 1991;34:5–10.
- Ambrose NG, Cox NJ, Yairi E: The genetic basis of persistence and recovery in stuttering. J Speech Lang Hear Res 1997;40:567–580.
- Viswanath N, Lee HS, Chakraborty R: Evidence for a major gene influence on persistent developmental stuttering. Hum Biol 2004;76:401–412.
McGuffin P, Owen MJ, Gottesman II: Psychiatric Genetics and Genomics. Oxford, Oxford University Press, 2005.
Shugart YY, Mundorff J, Kilshaw J, Doheny K, Doan B, Wanyee J, Green ED, Drayna D: Results of a genome-wide linkage scan for stuttering. Am J Med Genet 2004;124:133–135.
- Riaz N, Steinberg S, Ahmad J, Pluzhnikov A, Riazuddin S, Cox NJ, Drayna D: Genome-wide significant linkage to stuttering on chromosome 12. Am J Hum Genet 2005;76:647–651.
- Suresh R, Ambrose N, Roe C, Pluzhnikov A, Wittke-Thompson JK, Ng MCY, Wu X, Cook EH, Lundstrom C, Garsten M: New complexities in the genetics of stuttering: significant sex-specific linkage signals. Am J Hum Genet 2006;78:554–563.
- Wittke-Thompson JK, Ambrose N, Yairi E, Roe C, Cook EH, Ober C, Cox NJ: Genetic studies of stuttering in a founder population. J Fluency Disord 2007;32:33–50.
- Arndt J, Healey EC: Concomitant disorders in school-age children who stutter. Lang Speech Hear Serv Sch 2001;32:68–78.
- Healey EC, Reid R: ADHD and stuttering: a tutorial. J Fluency Disord 2003;28:79–93.
Riley G, Riley J: A revised component model for diagnosing and treating children who stutter. Contemp Issues Commun Sci Disord 2000;27:188–199.
- Lan J, Song M, Pan C, Zhuang G, Wang Y, Ma W, Chu Q, Lai Q, Xu F, Li Y: Association between dopaminergic genes (SLC6A3 and DRD2) and stuttering among Han Chinese. J Hum Genet 2009;54:457–460.
- Mazei-Robison MS, Couch RS, Shelton RC, Stein MA, Blakely RD: Sequence variation in the human dopamine transporter gene in children with attention deficit hyperactivity disorder. Neuropharmacology 2005;49:724–736.
- Reuter M, Peters K, Schroeter K, Koebke W, Lenardon B: The influence of the dopaminergic system on cognitive functioning: a molecular genetic approach. Behav Brain Res 2005;164:93–99.
- Mazei-Robison MS, Bowton E, Holy M, Schmudermaier M, Freissmuth M, Sitte HH, Galli A, Blakely RD: Anomalous dopamine release associated with a human dopamine transporter coding variant. J Neurosci 2008;28:7040–7046.
- Wu JC, Maguire G, Riley G, Lee A, Keator D, Tang C, Fallon J, Najafi A: Increased dopamine activity associated with stuttering. Neuroreport 1997;8:767–770.
- Maguire GA, Riley GD, Franklin DL, Maguire ME, Nguyen CT, Brojeni PH: Olanzapine in the treatment of developmental stuttering: a double-blind, placebo-controlled trial. Ann Clin Psychiatry 2004;16:63–67.
- Maguire GA, Yu BP, Franklin DL, Riley GD: Alleviating stuttering with pharmacological interventions. Expert Opin Pharmacother 2004;5:1565–1571.
- Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin JC, Drayna D: Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering. N Engl J Med 2010;362:677–685.
- Fisher SE: Genetic susceptibility to stuttering. N Engl J Med 2010;362:750–752.
- Büchel C, Watkins KE: Genetic susceptibility to persistent stuttering. N Engl J Med 2010;362:2226–2227.
Kraft SJ: Genome-Wide Association Study of Persistent Developmental Stuttering; PhD thesis University of Illinois, Urbana-Champaign, 2010.
- Pearson TA, Manolio TA: How to interpret a genome-wide association study. JAMA 2008;299:1335–1344.
- Hunter DJ, Altshuler D, Rader DJ: From Darwin’s finches to canaries in the coal mine - mining the genome for new biology. N Engl J Med 2008;358:2760–2763.
- Hirschhorn JN, Daly M: Genome-wide association studies for common diseases and complex traits. Nat Rev Gen 2005;6:95–108.
- Kitsios GD, Zintzaras E: Genomic convergence of genome-wide investigations for complex traits. Ann Hum Genet 2009;73:514–519.
- Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science 1996;273:1516–1517.
- Li M, Li C, Guan W: Evaluation of coverage variation of SNP chips for genome-wide association studies. Eur J Hum Genet 2008;16:635–643.
- Wang TH, Wang HS: A genome-wide association study primer for clinicians. Taiwan J Obstet Gynecol 2009;48:89–95.
Murphy AT, Fitzsimons RM: Stuttering and Personality Dynamics: Play Therapy, Projective Therapy, and Counseling. New York, Ronald Press, 1960.
- Stager S, Calis K, Grothe D, Block M, Berensen N, Smith P, Braun A: Treatment with medications affecting dopaminergic and sertonergic mechanisms: effects on fluency and anxiety in persons who stutter. J Fluency Disord 2005;30:319–335.
- Maguire G, Franklin D, Vatakis NG, Morgenshtern E, Denko T, Yaruss JS, Spotts C, Davis L, Davis A, Fox P, Soni P, Blomgren M, Silverman A, Riley G: Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the examining pagoclone for persistent developmental stuttering study. J Clin Psychopharmacol 2010;30:48–56.
- Chartier-Harlin M, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, Mullan M: Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 1991;353:844–846.
- Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM: Protein aggregation in the brain: the molecular basis for Alzheimer’s and Parkinson’s diseases. Mol Med 2008;14:451–464.
- Matsouka Y, Saito M, LaFrancois J, Saito M, Gaynor K, Olm V, Casey E, Yifan L, Shiratori C, Lemere C, Duff K: Novel therapeutic approach for the treatment of Alzheimer’s disease by peripheral administration of agents with an affinity to beta-amyloid. J Neurosci 2003;23:29–33.
- Dodel RC, Du Y, Depboylu C, Hampel H, Frolich L, Haag A, Hemmeter U, Paulsen S, Teipel SJ, Brettschneider S, Spottke A, Nolker C, Moller HJ, Wei X, Farlow M, Sommer N, Oertel WH: Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004;75:1472–1474.
- Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y-S, Huang X, Goldstein LE, Moir RD, Lim JT, Beyruether K, Zheng H, Tanzi RE, Masters CL, Bush AI: Treatment with a Copper-Zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 2001;30:665–676.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.