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What Do Researchers Know about Genetics and CAS?

Lawrence Shriberg, Ph.D., CCC-SLP

The primary findings on the genetics of CAS have emerged from studies of a London family (the ‘KE’ family), half of whose members have an orofacial apraxia and a reported apraxia of speech. Reviews of this widely-cited project include technical and more accessible descriptions of the mutation on the FOXP2 gene (located on chromosome 7) that has been linked to family members with CAS. A recent overview by researchers in the London-Oxford group that has studied the KE family for over 15 years provides a useful summary of the genomic and other findings, including a partially annotated bibliography (Vargha-Khadem et al., 2005). In response to the question posed in the present CAS forum, there is space for only brief comment on three aspects of this landmark research.

First, the neural phenotypes (i.e., characteristics) emerging from studies of FOXP2 by researchers in a number of disciplines are consistent with the behavioral phenotypes associated with CAS. FOXP2 is expressed widely in cells distributed throughout the brain, which is consistent with the cognitive, language, speech, prosody and other challenges observed in children with suspected CAS. Moreover, findings indicating that FOXP2 is expressed in both sides of the brain, rather than in just one hemisphere, are consistent with the severity and persistence of CAS during and often beyond the developmental period. Recent studies of several species of songbirds (Teramitsu et al., 2004) indicate that FOXP2 is especially active during the periods in which young birds learn their specific calls, providing an attractive animal model for studying comparable processes in children learning the speech and prosodic patterns of their language and local dialect. A complexity in this research is that the gene products of FOXP2 function primarily as switches that regulate other ‘downstream’ genes. Thus, although a great deal is known about FOXP2, the major challenge ahead is to understand the individual and collective effects of the downstream genes it controls-specifically, growth and development of the neural circuits underlying speech-language acquisition and performance. The London and Oxford research groups have recently received grants to do just that, using powerful techniques in bioinformatics and molecular neuroscience. Findings from these studies, which will be reported over the next few years, are expected to address fundamental questions about the developmental neurobiology of verbal trait disorders, including CAS.

A second promising development is that in the past year, three research groups have described case findings supporting the etiologic role of FOXP2 in CAS. The London-Oxford researchers recently reported that in a study of 43 children identified as having CAS, one child (and his affected sibling and their mother) had the same FOXP2 mutation observed in affected members of the KE family (MacDermot et al., 2004). A research group in the United States has reported CAS, as well as dysarthria, in a mother and daughter with a chromosome translocation in a region affecting FOXP2 (Shriberg et al., 2005). A Canadian group has identified a FOXP2 deficit in a child who reportedly has CAS, as well as a craniofacial dysmorphology (Zeesman et al., 2004).

Finally, although FOXP2 appears to be linked to CAS in these new case reports, it is likely that there are other genetic influences underlying alternative forms of CAS. Note that the FOXP2 mutation was identified in only one of the 43 children in the study cited above, leaving unexplained the origin of the other CAS diagnoses. Also, the FOXP2 mutation was not found in an unpublished study of children with suspected CAS (Barbara Lewis, personal communication). In addition to the idiopathic form of CAS (i.e., CAS occurring without other neurodevelopment involvements), apraxia of speech has been reported symptomatically in disorders such as Fragile X, autism, galactosemia, and some forms of epilepsy. Thus, another research challenge is to determine if there may be subtypes of CAS associated with different genetic backgrounds. On this issue, there appears to be notable recent convergence on the perspective that both typical and atypical communication development are controlled by common ‘generalist’ genes, rather than different ‘specialist’ genes (Plomin & Kovas, 2005.) This fundamental distinction is important for continuing research on the genetic origins of CAS. It suggests that in addition to searching for single genes underlying CAS, emphasis should also be placed on identifying interactions among groups of genes, each contributing to the form and severity of CAS. Information on such neural phenotypes, that may also be common to other verbal trait disorders, should in turn, help researchers better define and treat the behavioral characteristics of CAS.


MacDermot, K.D., Bonora, E., McKenzie, F., Smith, R.L., Sykes, N., Coupe, A-M., et al. (2004, October). Identification of FOXP2 truncation as a novel cause of nonsyndromic developmental speech disorder. Poster session presented at the annual meeting of The American Society of Human Genetics, Toronto, Canada.

Plomin, R. & Kovas, Y. (in press). Generalist genes and learning disabilities. Psychological Bulletin.
Shriberg, L.D., Ballard, K.J., Tomblin, J.B., Duffy, J.R., & Odell, K.H. (2005). Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2. Manuscript submitted for publication.

Teramitsu, I., Kudo, L.C., London, S.E., Geschwind, D.H., & White, S.A. (2004). Parallel FOXP1 and FOXP2 expression in songbird and human brain predicts functional interaction. Journal of Neuroscience, 24, 3152-3163.

Vargha-Khadem, F., Gadian, D.G., Copp, A., & Mishkin, M. (2005). FOXP2 and the neuroanatomy of speech and language. Neuroscience, 6, 131-138.
Zeesman, S., Nowaczyk, M.J.M., Teshima, I., Roberts, W., Oram Cardy, J., Brian, J., et al. (2004, October). Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 which involves FOXP2. Poster session presented at the annual meeting of The American Society of Human Genetics, Toronto, Canada.

[Dr. Lawrence Shriberg is Professor of Communication Disorders at the University of Wisconsin – Madison. Additionally, he is co-director of The Phonology Clinic and principal investigator on the Phonology Project at the Waisman Center. He is the chair of the ASHA Ad Hoc Committee on Apraxia of Speech in Children. Dr. Shriberg’s principal research interests focus on the nature and origin of childhood speech disorders, including studies to identify diagnostic markers for clinical subtypes and studies to develop subtype-specific treatment technologies, one such disorder being childhood apraxia of speech. He is also a member of CASANA’s Professional Advisory Board.]

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