Perspective | Published:

From genes to behavior in developmental dyslexia

Abstract

All four genes thus far linked to developmental dyslexia participate in brain development, and abnormalities in brain development are increasingly reported in dyslexia. Comparable abnormalities induced in young rodent brains cause auditory and cognitive deficits, underscoring the potential relevance of these brain changes to dyslexia. Our perspective on dyslexia is that some of the brain changes cause phonological processing abnormalities as well as auditory processing abnormalities; the latter, we speculate, resolve in a proportion of individuals during development, but contribute early on to the phonological disorder in dyslexia. Thus, we propose a tentative pathway between a genetic effect, developmental brain changes, and perceptual and cognitive deficits associated with dyslexia.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hinshelwood, J. Congenital Word-blindness (Lewis, London, 1917).

  2. 2

    Galaburda, A.M., Sherman, G.F., Rosen, G.D., Aboitiz, F. & Geschwind, N. Developmental dyslexia: four consecutive cases with cortical anomalies. Ann. Neurol. 18, 222–233 (1985).

  3. 3

    Drake, W.E. Clinical and pathological finding in a child with a developmental learning disability. J. Learn. Disabil. 1, 486–502 (1968).

  4. 4

    Chang, B.S. et al. Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia. Neurology 64, 799–803 (2005).

  5. 5

    de Vasconcelos Hage, S.R. et al. Specific language impairment: linguistic annd neurobiological aspects. Arq. Neuropsiquiatr. 64, 173–180 (2006).

  6. 6

    Galaburda, A.M., Menard, M.T. & Rosen, G.D. Evidence for aberrant auditory anatomy in developmental dyslexia. Proc. Natl. Acad. Sci. USA 91, 8010–8013 (1994).

  7. 7

    Nicolson, R., Fawcett, A.J. & Dean, P. Dyslexia, development and the cerebellum. Trends Neurosci. 24, 515–516 (2001).

  8. 8

    Fisher, S.E. & Francks, C. Genes, cognition and dyslexia: learning to read the genome. Trends Cogn. Sci. (in the press).

  9. 9

    Taipale, M. et al. A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Proc. Natl. Acad. Sci. USA 100, 11553–11558 (2003).

  10. 10

    Cope, N. et al. Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. Am. J. Hum. Genet. 76, 581–591 (2005).

  11. 11

    Paracchini, S. et al. The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum. Mol. Genet. 15, 1659–1666 (2006).

  12. 12

    Meng, H. et al. DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proc. Natl. Acad. Sci. USA 102, 17053–17058 (2005).

  13. 13

    Hannula-Jouppi, K. et al. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia. PLoS Genet. 1, e50 (2005).

  14. 14

    Wang, Y. et al. Dyx1c1/EKN1 plays a critical role in neuronal migration in developing neocortex. Neuroscience (in the press).

  15. 15

    S.E. & Shaywitz, B.A. A definition of dyslexia. Ann. Dyslexia 53, 1–14 (2003).

  16. 16

    Snowling, M.J. Dyslexia (Blackwell, Oxford, 2000).

  17. 17

    Ramus, F. Development dyslexia: specific psychological deficits or general sensormotor dysfunction current opinion in neurobiology 13:212–218 (2003).

  18. 18

    Wagner, R.K. & Torgesen, J.K. The nature of phonological processing and its causal role in the acquisition of reading skills. Psychol. Bull. 101, 192–212 (1987).

  19. 19

    Stein, J. & Walsh, V. To see but not to read; the magnocellular theory of dyslexia. Trends Neurosci. 20, 147–152 (1997).

  20. 20

    Valdois, S., Bosse, M.-L. & Tainturier, M.-J. The cognitive deficits responsible for developmental dyslexia: Review of evidence for a selective visual attentional disorder. Dyslexia 10, 339–363 (2004).

  21. 21

    Eckert, M. Neuroanatomical markers for dyslexia: a review of dyslexia structural imaging studies. Neuroscientist 10, 362–371 (2004).

  22. 22

    White, S. et al. A double dissociation between sensorimotor impairments and reading disability: a comparison of autistic and dyslexic children. Cogn. Neuropsychol. 23, 748–761 (2006).

  23. 23

    Bishop, D.V.M. & Snowling, M.J. Developmental dyslexia and specific language impairment: same or different? Psychol. Bull. 130, 858–886 (2004).

  24. 24

    Hill, E.L. Non-specific nature of specific language impairment: a review of the literature with regard to concomitant motor impairments. Int. J. Lang. Commun. Disord. 36, 149–171 (2001).

  25. 25

    Butterworth, B. Developmental dyscalculia. in Handbook of Mathematical Cognition (ed. Campbell, J.I.D.) 455–467 (Psychology Press, New York, 2005).

  26. 26

    Leonard, C.M. et al. Anatomical risk factors that distinguish dyslexia from SLI predict reading skill in normal children. J. Commun. Disord. 35, 501–531 (2002).

  27. 27

    Smith, S.D., Kimberling, W.J., Pennington, B.F. & Lubs, H.A. Specific reading disability: Identification of an inherited form through linkage analysis. Science 219, 1345–1347 (1983).

  28. 28

    Pennington, B.F. et al. Evidence for major gene transmission of developmental dyslexia. J. Am. Med. Assoc. 266, 1527–1534 (1991).

  29. 29

    Cardon, L.R. et al. Quantitative trait locus for reading disability on chromosome 6. Science 266, 276–279 (1994).

  30. 30

    Allen, K.M., Gleeson, J.G., Shoup, S.M. & Walsh, C.A.A. YAC contig in Xq22.3-q23, from DXS287 to DXS8088, spanning the brain-specific genes doublecortin (DCX) and PAK3. Genomics 52, 214–218 (1998).

  31. 31

    des Portes, V. et al. doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH). Hum. Mol. Genet. 7, 1063–1070 (1998).

  32. 32

    Deuel, T.A. et al. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron 49, 41–53 (2006).

  33. 33

    Koizumi, H., Tanaka, T. & Gleeson, J.G. Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration. Neuron 49, 55–66 (2006).

  34. 34

    Coquelle, F.M. et al. Common and divergent roles for members of the mouse DCX superfamily. Cell Cycle 5, 976–983 (2006).

  35. 35

    Wigg, K.G. et al. Support for EKN1 as the susceptibility locus for dyslexia on 15q21. Mol. Psychiatry 9, 1111–1121 (2004).

  36. 36

    Chapman, N.H. et al. Linkage analyses of four regions previously implicated in dyslexia: confirmation of a locus on chromosome 15q. Am. J. Med. Genet. B Neuropsychiatr. Genet. 131, 67–75 (2004).

  37. 37

    Marino, C. et al. A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia. Eur. J. Hum. Genet. 13, 491–499 (2005).

  38. 38

    LoTurco, J.J., Wang, Y. & Paramasivam, M. Neuronal migration and dyslexia susceptibility. in The Dyslexic Brain: New Pathways in Neuroscience Discovery (ed. Rosen, G.D.) 119–128 (Lawrence Erlbaum Associates, Mahwah, New Jersey, 2006).

  39. 39

    Erskine, L. et al. Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J. Neurosci. 20, 4975–4982 (2000).

  40. 40

    Yuan, W. et al. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev. Biol. 212, 290–306 (1999).

  41. 41

    Zhu, Y., Li, H., Zhou, L., Wu, J.Y. & Rao, Y. Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex. Neuron 23, 473–485 (1999).

  42. 42

    Rutter, M. et al. Sex differences in developmental reading disability: new findings from 4 epidemiological studies. J. Am. Med. Assoc. 291, 2007–2012 (2004).

  43. 43

    Rosen, G.D., Herman, A.E. & Galaburda, A.M. Sex differences in the effects of early neocortical injury on neuronal size distribution of the medial geniculate nucleus in the rat are mediated by perinatal gonadal steroids. Cereb. Cortex 9, 27–34 (1999).

  44. 44

    Rosen, G.D., Burstein, D. & Galaburda, A.M. Changes in efferent and afferent connectivity in rats with cerebrocortical microgyria. J. Comp. Neurol. 418, 423–440 (2000).

  45. 45

    Denenberg, V.H., Sherman, G.F., Schrott, L.M., Rosen, G.D. & Galaburda, A.M. Spatial learning, discrimination learning, paw preference and neocortical ectopias in two autoimmune strains of mice. Brain Res. 562, 98–104 (1991).

  46. 46

    Rosen, G.D., Waters, N.S., Galaburda, A.M. & Denenberg, V.H. Behavioral consequences of neonatal injury of the neocortex. Brain Res. 681, 177–189 (1995).

  47. 47

    Peiffer, A.M., Friedman, J.T., Rosen, G.D. & Fitch, R.H. Impaired gap detection in juvenile microgyric rats. Brain Res. Dev. Brain Res. 152, 93–98 (2004).

  48. 48

    Fitch, R.H., Tallal, P., Brown, C., Galaburda, A.M. & Rosen, G.D. Induced microgyria and auditory temporal processing in rats: a model for language impairment? Cereb. Cortex 4, 260–270 (1994).

  49. 49

    Clark, M.G., Rosen, G.D., Tallal, P. & Fitch, R.H. Impaired two-tone processing at rapid rates in male rats with induced microgyria. Brain Res. 871, 94–97 (2000).

Download references

Acknowledgements

This work was supported by US National Institutes of Health grant HD20806 and by the The Dyslexia Foundation, and by grants from the Ville de Paris and the European Commission NEURODYS Project.

Author information

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Further reading

Figure 1: Protein domains and possible functions.
Figure 2: Human and animal neocortical malformations.