A pronounced speech and language disorder affecting half of the 30 members of the four-generational KE family has been attributed by some researchers to a specific defect in the generation of morphosyntactic rules. The reported selectivity of the impairment has led to the view that the affected members suffer from a grammar-specific disorder. Our investigations of the same KE family indicate that the inherited disorder has a broad phenotype which transcends impaired generation of syntactical rules and includes a striking articulatory impairment as well as defects in intellectual, linguistic, and orofacial praxic functions generally. Although the evidence from this family thus provides no support for the existence of "grammar genes," their linguistic difficulties do constitute a prominent part of their phenotype. Investigations of the neural and genetic correlates of their disorder could therefore uncover important clues to some of the bases of the primary human faculties of speech and language.

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., VarghaKhadem, 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.