ebbs logo Faraneh Vargha-Khadem

University College London Institute of Child Health
and
Great Ormond Street Hospital for Children
London, UK

From speech to gene: FOXP2 and the KE family

Fifteen of the 30 three-generational KE family members suffer from an orofacial and verbal dyspraxia arising from an underlying impairment in the rapid selection and accurate sequencing of orofacial movements most evident in speech. Structural neuroimaging in the affected members revealed bilateral abnormalities in a number of motor, and speech and language-related brain regions. Functional neuroimaging during verb generation and repetition tasks disclosed a distinctly atypical pattern of activation (i.e. diffuse, bilateral, and located predominantly in posterior cortical regions). Comparison between affected and unaffected family members indicated that the FOXP2 mutation is associated with significant underactivation in several regions that had been found to be morphologically abnormal, including the inferior frontal gyrus. Together, these structural and functional MR results provide a coherent explanation for the affected members' striking and persistent disorder.

The neuropsychological and neuroimaging findings will be related to the genetic basis of the disorder in the KE family and to that of other cases with mutations and/or deletions of the FOXP2 gene, and to the pattern of gene expression during embryological development in humans, mice and songbirds. The convergence of data from the behavioural, neuroimaging, and gene expression studies lead to a tentative model of the neuroanatomy of the speech and language system.