Towards the elucidation of the genetic and brain bases of developmental speech and language disorders

Two papers in this issue of Brain by Watkins and colleagues (Watkins et al ., 2002 a , b ) provide fascinating and important new data about the core behavioural features and neural basis of an inherited form of speech and language disorder. This work is particularly relevant in the light of recent discoveries about the genetic basis of the same developmental disorder. Individuals affected by developmental speech and language disorders have major difficulties acquiring expressive and/or receptive language despite adequate intelligence and opportunity, and in the absence of any profound sensory or neurological impairment (Bishop et al ., 1995). Although twin studies consistently show a significant genetic component, the majority of families show a complex pattern of inheritance. The present studies concern the unique three‐generation pedigree, the KE family, in whom a severe speech and language disorder is transmitted as an autosomal‐dominant monogenetic trait. Speech in affected individuals is effortful, distorted and often unintelligible with word order and other grammatical errors. Previous work on the KE family had mapped the locus responsible (SPCH1) to 7q31 (Fisher et al ., 1998). Further studies by the same research group have now identified a point mutation in affected family members, which alters an invariant amino acid residue in the DNA‐binding domain in a forkhead/winged helix transcription factor, encoded by the FOXP2 gene (Lai et al ., 2001). The case for a causal association is further strengthened by the finding of a translocation break in the same gene in another unrelated individual who has a very similar speech and language disorder (Lai et al ., 2001). Many members of the forkhead/winged helix protein family are known to be regulators of embryogenesis and mutations of the FOX genes have been implicated in a range of other human developmental disorders. Lai et al . (2001) propose …