Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development.

Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.

A systematic review of the academic achievement of primary and secondary school-aged students with developmental language disorder.

Background and aims: The ability to communicate is a fundamental skill required to participate in school. Students with Developmental Language Disorder (DLD) have persistent and significant language difficulties that impact daily functioning. However, the impact of DLD on the academic achievement of primary and secondary school-aged students has received limited attention. Methods: A systematic review of the empirical research published between 2008 and 2020 was undertaken to identify studies that have examined the academic achievement of school-aged students with DLD within curriculum areas. A total of 44 studies were identified that met inclusion criteria for review. Results: Students with DLD demonstrated difficulties with academic achievement across all measured curriculum areas compared to their typically developing peers. Most studies focused on literacy skills, including reading, spelling, writing and narratives. Conclusions and implications: The performance of students with DLD was heterogeneous with individual students demonstrating relative strengths in some areas of academic achievement. The implications of these results for educational practices and future research are discussed.