The Importance of Deep Speech Phenotyping for Neurodevelopmental and Genetic Disorders: a Conceptual Review

Background: Speech is the most common modality through which language is communicated, and delayed, disordered, or absent speech production is a hallmark of many neurodevelopmental and genetic disorders. Yet, speech is not often carefully phenotyped in neurodevelopmental disorders. In this paper, we argue that such deep phenotyping, defined as phenotyping that is specific to speech production and not conflated with language or cognitive ability, is vital if we are to understand how genetic variations affect the brain regions that are associated with spoken language. Speech is distinct from language, though the two are related behaviorally and share neural substrates. We present a brief taxonomy of developmental speech production disorders, with particular emphasis on the motor speech disorders childhood apraxia of speech (a disorder of motor planning) and childhood dysarthria (a set of disorders of motor execution). We review the history of discoveries concerning the KE family, in whom a hereditary form of communication impairment was identified as childhood apraxia of speech and linked to dysfunction in the FOXP2 gene. The story demonstrates how instrumental deep phenotyping of speech production was in this seminal discovery in the genetics of speech and language. There is considerable overlap between the neural substrates associated with speech production and with FOXP2 expression, suggesting that further genes associated with speech dysfunction will also be expressed in similar brain regions. We then show how a biologically accurate computational model of speech production, in combination with detailed information about speech production in children with developmental disorders, can generate testable hypotheses about the nature, genetics, and neurology of speech disorders.

Conclusions: Though speech and language are distinct, specific types of developmental speech disorder are associated with far-reaching effects on verbal communication in children with neurodevelopmental disorders. Therefore, detailed speech phenotyping, in collaboration with experts on pediatric speech development and disorders, can lead us to a new generation of discoveries about how speech development is affected in genetic disorders.