Genetics of Speech and Language Disorders

Abstract

Vocal communication mediated by speech and language is a uniquely human trait, and has served an important evolutionary role in the development of our species. Deficits in speech and language functions can be of numerous types, including aphasia, stuttering, articulation disorders, verbal dyspraxia, and specific language impairment; language deficits are also related to dyslexia. Most communication disorders are prominent in children, where they are common. A number of these disorders have been shown to cluster in families, suggesting that genetic factors are involved, but their etiology at the molecular level is not well understood. In the past decade, genetic methods have proven to be powerful for understanding these etiologies. Linkage studies and molecular genetic analyses in a large family containing multiple individuals affected with verbal dyspraxia led to the discovery of mutations in the FOXP2 gene. This gene encodes a forkhead domain transcription factor, a finding that has led researchers to a new avenue of investigation into the substrates and mechanisms that underlie human speech development. In studies of stuttering, linkage and candidate gene approaches in consanguineous families identified mutations in the lysosomal enzyme-targeting pathway genes GNPTAB, GNPTG, and NAGPA, revealing a role for inherited defects in cell metabolism in this disorder. In specific language impairment, linkage studies have identified several loci, and candidate gene association studies are making progress in identifying causal variants at these loci. Although only a small fraction of all cases of speech and language disorders can be explained by genetic findings to date, the significant progress made thus far suggests that genetic approaches will continue to provide important avenues for research on this group of disorders.

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits

“…This strategy has facilitated the identification of genes or chromosomal loci implicated in other learning disorders, such as developmental verbal dyspraxia. 33,34 Executive function or WM deficits have been reported in genetic neurodevelopmental disorders associated with ID and physical abnormalities, like Down's syndrome or Williams syndrome. 35,36 Various approaches, including linkage analysis and association studies, have indicated various candidate genes, such as ROBO1 or CHD13, associated with low WM performances as a specific endophenotype of a cognitive dysfunction.…”

Insights into the Genetic Foundations of Human Communication

“…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.…”

Recent advances in genetic studies of stuttering

“…Although speech and language are not easily distinguished, they are different from each other [1]. Speech is defined as the mechanical aspect of vocalization for communication, and includes articulation, voice and fluency.…”