Neural basis of an inherited speech and language disorder - PubMed
- ️Thu Jan 01 1998
. 1998 Oct 13;95(21):12695-700.
doi: 10.1073/pnas.95.21.12695.
K E Watkins, C J Price, J Ashburner, K J Alcock, A Connelly, R S Frackowiak, K J Friston, M E Pembrey, M Mishkin, D G Gadian, R E Passingham
Affiliations
- PMID: 9770548
- PMCID: PMC22893
- DOI: 10.1073/pnas.95.21.12695
Neural basis of an inherited speech and language disorder
F Vargha-Khadem et al. Proc Natl Acad Sci U S A. 1998.
Abstract
Investigation of the three-generation KE family, half of whose members are affected by a pronounced verbal dyspraxia, has led to identification of their core deficit as one involving sequential articulation and orofacial praxis. A positron emission tomography activation study revealed functional abnormalities in both cortical and subcortical motor-related areas of the frontal lobe, while quantitative analyses of magnetic resonance imaging scans revealed structural abnormalities in several of these same areas, particularly the caudate nucleus, which was found to be abnormally small bilaterally. A recent linkage study [Fisher, S., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembry, M. E. (1998) Nat. Genet. 18, 168-170] localized the abnormal gene (SPCH1) to a 5. 6-centiMorgan interval in the chromosomal band 7q31. The genetic mutation or deletion in this region has resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, leading to marked disruption of speech and expressive language.
Figures

Pedigree of KE family. Roman numerals indicate the generation, and Arabic numerals, the member’s pedigree number within a generation. Affected members, filled shapes; unaffected members, open shapes; females, circles; males, squares; /, deceased; ∧, twins.

(a) Word and nonword repetition. Bars indicate mean percent correct for the groups of affected and unaffected family members (n = 13 and 10, respectively). Filled bars, affected group; open bars, unaffected group; small squares, scores of individual family members. Note the absence of overlap between the scores of the two groups on both tests. (b) Simultaneous and sequential orofacial movements to command. Bars indicate mean percent correct for the group of affected family members and the normal control group (n = 11 and 52, respectively). Filled bar, affected group; open bar, control group; small squares, scores of individuals (for clarity, the same score obtained by two or more control subjects is marked by a single square). Again note the absence of overlap between the scores of the two groups, except for one statistical outlier (a 45-year-old male) in the control group.

Results of SPM analysis of PET data (A and B; see also Table 1) and MRI data (C; see also Table 2). (A) Parasagittal section through left hemisphere, 6 mm from midline. Colored area, encompassing parts of SMA, preSMA, and cingulate cortices, indicates a region that was less active in the affected family members than in the controls. (B) Coronal section, 14 mm in front of the coronal plane through the anterior commissure. Colored areas, located in the head of the left caudate nucleus and left premotor cortex, indicate regions that were more active in the affected family members than in the controls. (C) Transverse section, 2 mm above the transverse plane through the anterior and posterior commissures. Colored areas, located in the head of the caudate nucleus bilaterally, indicate areas that had less gray matter in the group of affected than in the group of unaffected family members (n = 6 and 7, respectively).
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