Abstract
Stuttering is a disorder characterized by interruptions in the flow and alterations in the rhythm of speech, including the repetition of sounds, syllables, and words, as well as blocks and prolongations. This disfluency can cause distress to those who stutter due to discomfort and insecurity during the social interaction process mediated by language. A better understanding of the causal mechanisms of stuttering can aid in the development of more effective treatment strategies. The aim of this study is a narrative review of the literature on the advances in knowledge regarding the role of genetics in the etiology of developmental stuttering. Twin studies conducted in various countries, although with varying results, mostly indicate that the genetic component has greater importance in the etiology of developmental stuttering than environmental factors. In the past 20 years, there has been significant progress in this field with the discovery of mutant genes related to stuttering and the study of mice in which these mutant genes were introduced. All this advancement points to a progressive increase in the understanding of the neural bases of developmental stuttering and its various phenotypes, with the potential to favor the development of individualized and more effective treatments for those who stutter.
References
ADECK, A. et al. Morphological deficits of glial cells in a transgenic mouse model for developmental stuttering. , 5 jan. 2024. https://doi.org/10.1101/2024.01.04.574051.
ANDREWS, G. et al. Genetic factors in stuttering confirmed. Archives of general psychiatry, v. 48, n. 11, p. 1034–5, nov. 1991.
BARNES, T. D. et al. A Mutation Associated with Stuttering Alters Mouse Pup Ultrasonic Vocalizations. Current Biology, v. 26, n. 8, p. 1009–1018, abr. 2016.
BELOW, J. et al. Discovery of 36 loci significantly associated with stuttering. , 26 abr. 2023. https://doi.org/10.21203/rs.3.rs-2799926/v1.
BLOODSTEIN, O.; RATNER, N. B. A Handbook on Stuttering. 6th. ed. Clifton Park, NY: Cengage Learning, 2008.
CO, M.; ANDERSON, A. G.; KONOPKA, G. FOXP transcription factors in vertebrate brain development, function, and disorders. WIREs Developmental Biology, v. 9, n. 5, p. e375, set. 2020. https://doi.org/10.1002/wdev.375.
Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed ed. Washington: American psychiatric association, 2013.
DWORZYNSKI, K. et al. Genetic Etiology in Cases of Recovered and Persistent Stuttering in an Unselected, Longitudinal Sample of Young Twins. American Journal of Speech-Language Pathology, v. 16, n. 2, p. 169, 1 maio 2007. https://doi.org/10.1044/1058-0360(2007/021).
FAGNANI, C. et al. Heritability and environmental effects for self-reported periods with stuttering: A twin study from Denmark. Logopedics Phoniatrics Vocology, v. 36, n. 3, p. 114–120, 17 out. 2011. https://doi.org/10.3109/14015439.2010.534503.
FELSENFELD, S.; PLOMIN, R. Epidemiological and offspring analyses of developmental speech disorders using data from the Colorado Adoption Project. Journal of speech, language, and hearing research : JSLHR, v. 40, n. 4, p. 778–91, ago. 1997.
FISH, E. W. et al. Distress vocalizations in maternally separated mouse pups: modulation via 5-HT 1A , 5-HT 1B and GABA A receptors. Psychopharmacology, v. 149, n. 3, p. 277–285, 25 abr. 2000. https://doi.org/10.1007/s002130000370.
GUITAR, B.; CONTURE, E. G. The child who stutters: to the pediatrician. 4th ed ed. Memphis: Stuttering Foundation of America, 2006.
HOLY, T. E.; GUO, Z. Ultrasonic Songs of Male Mice. PLoS Biology, v. 3, n. 12, p. e386, 1 nov. 2005. https://doi.org/10.1371/journal.pbio.0030386.
KANG, C. et al. Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering. New England Journal of Medicine, v. 362, n. 8, p. 677–685, 25 fev. 2010. https://doi.org/10.1056/NEJMoa0902630.
KAZEMI, N. et al. Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers. Gene, v. 647, p. 93–100, mar. 2018. https://doi.org/10.1016/j.gene.2017.12.054.
KHAN, S. A.; TOMATSU, S. C. Mucolipidoses Overview: Past, Present, and Future. International Journal of Molecular Sciences, v. 21, n. 18, p. 6812, 17 set. 2020. https://doi.org/10.3390/ijms21186812.
KONOPKA, G.; ROBERTS, T. F. Animal Models of Speech and Vocal Communication Deficits Associated With Psychiatric Disorders. Biological Psychiatry, v. 79, n. 1, p. 53–61, jan. 2016. https://doi.org/10.1016/j.biopsych.2015.07.001.
LAI, C. S. L. et al. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, v. 413, n. 6855, p. 519–523, 4 out. 2001. https://doi.org/10.1038/35097076.
MORGAN, A. T. et al. Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40. Brain, v. 146, n. 12, p. 5086–5097, 1 dez. 2023. https://doi.org/10.1093/brain/awad314
MORGAN, A. T. et al. Genetic architecture of childhood speech disorder: a review. Molecular Psychiatry, 16 fev. 2024. https://doi.org/10.1038/s41380-024-02409-8.
OOKI, S. Genetic and Environmental Influences on Stuttering and Tics in Japanese Twin Children. Twin Research and Human Genetics, v. 8, n. 01, p. 69–75, 21 fev. 2005. https://doi.org/10.1375/twin.8.1.69.
RAUTAKOSKI, P. et al. Genetic and environmental effects on stuttering: A twin study from Finland. Journal of Fluency Disorders, v. 37, n. 3, p. 202–210, set. 2012. https://doi.org/10.1016/j.jfludis.2011.12.003.
RAZA, M. H. et al. Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering. The American Journal of Human Genetics, v. 97, n. 5, p. 715–725, nov. 2015. https://doi.org/10.1016/j.ajhg.2015.10.007.
VAN BEIJSTERVELDT, C. E. M.; FELSENFELD, S.; BOOMSMA, D. I. Bivariate Genetic Analyses of Stuttering and Nonfluency in a Large Sample of 5-Year-Old Twins. Journal of Speech Language and Hearing Research, v. 53, n. 3, p. 609, 1 jun. 2010.
YAIRI, E.; AMBROSE, N. Epidemiology of stuttering: 21st century advances. Journal of Fluency Disorders, v. 38, n. 2, p. 66–87, jun. 2013.
YAIRI, E.; AMBROSE, N. G. Early childhood stuttering I: persistency and recovery rates. Journal of speech, language, and hearing research : JSLHR, v. 42, n. 5, p. 1097–112, out. 1999. https://doi.org/10.1016/j.jfludis.2012.11.002.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2024 Amanda Peixoto Silva, Marjorie Vasconcelos Porto , Lidiane Peixoto de Souza Silva, Welington dos Santos Silva