Molecular genetics of disorders of spoken and written language

Behavioral data and DNA are collected from multigenerational families and sporadically affected children with severe familial or sporadic speech/language/reading disorders towards identifying causal genes and building a biologically based disorder subtype catalog. Recent discoveries of candidate regions and genes include BCL11A (Peter et al., 2014), 6q25.3 (Peter et al., 2017), CDH18, and C4orf21 (ZGRF1) (Peter et al., 2016).

Multidisciplinary study of deficit in rapid sequential processing as a genetic biomarker of dyslexia and apraxia

Multidisciplinary data are collected from individuals and families with dyslexia. The aim is to generate converging evidence of slowed and disorganized information processing across multiple modalities (behaviors, cortical electrophysiology, brainstem electrophysiology, structural and functional whole-brain imaging) and to identify genetic etiologies of biomarkers. Similar to the speech genetics study, long-germ goals are to develop preventative and early interventions for infants at genetic risk for dyslexia. Recent findings are that adults with dyslexia and adults with a history of childhood apraxia of speech have difficulty maintaining the order of elements in sequences during a variety of tasks, for instance the order of sounds when imitating nonwords and the order of letters when reading nonwords (Peter et al., 2017, Peter 2017).

Development of early intervention/prevention approaches in infants at genetic risk for speech disorders

Certain medical disorders of genetic origin carry a high risk of speech difficulties. We recently launched the Babble Boot Camp, a program of preventive activities and routines developed for a cohort of infants at genetic risk for severe speech and language disorders. The children all have a diagnosis of classic galactosemia (CG), a metabolic disease that is diagnosed via newborn screening and that puts the children at very high risk of speech and language disorders. Children with CG typically receive the same assessment and treatment services as children with speech and language disorders of unknown cause. We are leveraging the fact that CG, and hence, the risk for speech and language disorders, is known at birth towards the first clinical trial of preventive, rather than remediative, services. A pediatric speech-language pathologists trains parents to support earliest signals of communication, earliest vocalizations, babble, first words, vocabulary growth, word combinations, and verbal interactions. The pilot cohort consists of 15 families, each with a child with CG. Initial results from the first children completing the program are encouraging, and we hope to start a larger clinical trial in the near future.

Some of the highlights of our recent work:

Sequential processing deficits persist in adults with histories of childhood apraxia of speech and dyslexia.

Peter, B., Lancaster, H., Vose, C., Stoel-Gammon, C., and Middleton, K. (2017). Sequential processing deficit as a shared persisting biomarker in dyslexia and childhood apraxia of speech. Clinical Linguistics & Phonetics. DOI:10.1080/02699206.2017.1375560

Different genetic variations can produce similar phenotypes in families with familial childhood apraxia of speech, and the implicated genes are highly expressed in the cerebellum.

Peter, B., Wijsman, E., Nato, A., University of Washington Centers for Mendelian Genomics, Matsushita, M., Chapman, K., Stanaway, I., Wolff, J., Oda, K. & Raskind, W. (2016). Genetic candidate variants in two multigenerational families with childhood apraxia of speech. PLoS One 11(4) e0153864, doi:10.1371/journal.pone.0153864, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153864

Peter, B., Hogan, T., Alt, M., Green, S., Cowan, N., Schrauwen, I., Naymik, M., Sacchetta, M., Vose, C., Deshpande, K., Guido, J., & Gray, S. (2018). Copy-number variations in children with disorders of spoken and written language point to genes with prenatal cerebellar expression. American Society of Human Genetics Meeting, San Diego, Oct. 16-20, 2018.