Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia

Abstract

The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.

Figure 1

Illustration of unilateral (A) and bilateral (B) methods of VBM analysis. LH, left hemisphere; RH, right hemisphere.

Figure 2

Result of the bilateral conjuction analysis. Less grey matter density in the caudate nuclei in the affected members. Left and right caudate nuclei, uncorrected P < 0.001 at coordinates ± 13 20 3.