Genetic Advances in the Study of Speech and Language Disorders

Abstract

SummaryDevelopmental speech and language disorders cover a wide range of childhood conditions with overlapping but heterogeneous phenotypes and underlying etiologies. This characteristic heterogeneity hinders accurate diagnosis, can complicate treatment strategies, and causes difficulties in the identification of causal factors. Nonetheless, over the last decade, genetic variants have been identified that may predispose certain individuals to different aspects of speech and language difficulties. In this review, we summarize advances in the genetic investigation of stuttering, speech-sound disorder (SSD), specific language impairment (SLI), and developmental verbal dyspraxia (DVD). We discuss how the identification and study of specific genes and pathways, including FOXP2, CNTNAP2, ATP2C2, CMIP, and lysosomal enzymes, may advance our understanding of the etiology of speech and language disorders and enable us to better understand the relationships between the different forms of impairment across the spectrum.

Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development

“…4). In addition, mutations in CNTNAP2 also have been linked to epilepsy (5-7), Tourette syndrome (8,9), schizophrenia (5,7,10), attention deficit hyperactivity disorder (ADHD) (11), learning disability (12,13), and language impairment (14)(15)(16). Thus, CNTNAP2 is of central importance for human brain function, as additionally shown by recent in vivo MRI studies in which variations in the CNTNAP2 gene were associated with reduced frontal gray matter and altered functional connectivity (17,18).…”

Insights into the Genetic Foundations of Human Communication

“…Still, there remains a substantial number of children whose speech or language problems occur in the absence of any obvious explanatory factors. There is considerable evidence of a substantial genetic component to these unexplained speech and language impairments (Newbury and Monaco 2010;CarrionCastillo et al 2013). Studies of such disorders not only have clinical and educational relevance, but can also help answer fundamental questions about the genetic architecture underpinning human speech and language.…”

“…Therefore, in addition to the situation where one phenotype corresponds to many genotypes, we can also expect that one genotype corresponds to multiple phenotypes. Table 2 outlines the range of experimental paradigms that have been applied to molecular studies of developmental communication disorders to tackle their heterogeneous genetic architecture and make best use of available resources (Newbury and Monaco 2010;Kang and Drayna 2011;Deriziotis and Fisher 2013;Newbury et al 2014). This research field is at a relatively early stage of development and studies need (when possible) to take an unbiased genomewide approach to gene-hunting.…”

“…The difficulty in classifying SSD arises partly because it can include both articulatory and phonological deficits (see Table 1). The presence of phonological deficits has also suggested etiological overlap with dyslexia, and some genomic regions linked to dyslexia have shown linkage to SSD (Newbury and Monaco 2010). Additional genomic loci in SSD have been identified more recently, but no candidate genes have been pinpointed within any of the reported linkage intervals (Peter et al 2012).…”

“…Language impairments and reading/spelling difficulties show high levels of comorbidity, which suggests a possible common genetic etiology (Pennington and Bishop 2009). The initial leads in unravelling the genetic basis of these disorders came from linkage studies first reported over 15 years ago, which mapped several genomic loci that might contain risk genes (CarrionCastillo et al 2013;Newbury and Monaco 2010;Fisher and DeFries 2002). Linkage studies highlight broad chromosomal intervals containing many different genes.…”