Abstract
Childhood speech and language deficits are highly prevalent and are a common feature of neurodevelopmental disorders. However, it is difficult to investigate the underlying causal pathways because many diagnostic groups have a heterogeneous aetiology. Studying disorders with a shared genetic cause and shared cognitive deficits can provide crucial insight into the cellular mechanisms and neural systems that give rise to those impairments. The current study investigated structural brain differences of individuals with mutations in ZDHHC9, which is associated with a specific neurodevelopmental phenotype including prominent speech and language impairments and intellectual disability. We used multiple structural neuroimaging methods to characterise neuroanatomy in this group, and observed bilateral reductions in cortical thickness in areas surrounding the temporo-parietal junction, parietal lobule, and inferior frontal lobe, and decreased microstructural integrity of cortical, subcortical-cortical, and interhemispheric white matter projections. These findings are compared to reports for other genetic groups and genetically heterogeneous disorders with a similar presentation. Overlap in the neuroanatomical phenotype suggests a common pathway that particularly affects the development of temporo-parietal and inferior frontal areas, and their connections.
Highlights
Childhood speech and language problems are highly prevalent, but the neurodevelopmental mechanisms contributing to these impairments are not well understood (Grigorenko, 2009; Newbury and Monaco, 2010; Webster and Shevell, 2004)
Preliminary neuro-radiological assessment and volumetric analyses indicated no gross morphological abnormalities in the ZDHHC9 group other than hypoplasia of the corpus callosum and reduced volume of subcortical structures including the thalamus and striatum (Baker et al, 2015). We extended these initial observations by measuring the impact of ZDHHC9 mutation on brain organisation using MRI focussing on global and regional cortical thickness and surface area, and on white-matter integrity
Cortical thickness Comparison of mean cortical thickness across the entire cortical surface indicated a significant main effect of participant group with lower mean cortical thickness in the ZDHHC9 group
Summary
Childhood speech and language problems are highly prevalent, but the neurodevelopmental mechanisms contributing to these impairments are not well understood (Grigorenko, 2009; Newbury and Monaco, 2010; Webster and Shevell, 2004). Developmental speech and language problems typically have a heterogeneous aetiology; this variability means that despite their general prevalence it is difficult to identify the pathways (biochemical, cellular, neural systems) that result in these cognitive deficits. It is increasingly possible to identify small groups of individuals who share the same rare genetic cause of developmental language disorder. Rare, neuroimaging studies of disorders that combine aetiological homogeneity with cognitive specificity offer a unique window into the dysregulation of brain systems relevant to common neurodevelopmental disorders in the general population. The study of a rare familial speech disorder (KE family, FOXP2 mutation) has highlighted the importance of striatal systems and cortico-striatal networks for
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