Children with autism and related disorders often have problems with language acquisition. Simon Fisher of Oxford University and his colleagues are aiming to uncover the neural mechanisms of abnormal language development by studying the key genetic pathways that can go awry in these disorders.

Family and twin studies have shown that children’s genetic makeup plays a major role in their risk of developing language problems. Fisher and his colleagues previously identified FOXP2 as the first example of a gene linked to speech and language deficits. Children with FOXP2 mutations have difficulties mastering the complex sequences of mouth movements needed for speech, along with impairments in various aspects of language. FOXP2 is also present in non-speaking animals, where it is important for brain circuits involved in learning sequences of muscle movements. In the brains of songbirds, for instance, inactivation of FOXP2 interferes with their vocal imitation skills during song learning.

FOXP2 functions by switching other genes on and off. In 2008, Fisher and his colleagues found that genes regulated by FOXP2 in the human brain can be more broadly involved in common language impairments. The researchers identified CNTNAP2 as a target of FOXP2 that is itself associated with typical cases of specific language impairment, a developmental disorder with some similarities to autism. CNTNAP2 has also been linked to autism in other studies, particularly with regard to delays in language development.

Using FOXP2 as a molecular entry point, Fisher and colleagues aim to identify other genetic mechanisms contributing to language problems in autism and related disorders. The researchers will use state-of-the-art genomic methods to define the networks of genes downstream of FOXP2 in the brain, and to determine how mutations in FOXP2 disrupt these pathways. They plan to later assess whether the identified genes are associated with specific language impairment or autism in cohorts of affected children.

The findings should shed new light on the origins of language problems in these disorders, and may ultimately improve their diagnosis and treatment.