Neural basis of an inherited speech and language disorder

TLDR

A linkage study identified the SPCH1 gene on chromosome 7q31 as associated with the disorder. A mutation or deletion in SPCH1 disrupts development of frontal lobe motor regions and the caudate nucleus, impairing orofacial movements and sequential articulation. Affected family members exhibit a core deficit in sequential articulation and orofacial praxis, accompanied by functional PET and structural MRI abnormalities in frontal motor areas and a bilaterally small caudate nucleus. Citation: Fisher et al., Nat.

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.