Corpus callosum metrics predict severity of visuospatial and neuromotor dysfunctions in ARID1B mutations with Coffin–Siris syndrome

Abstract

ARID1B mutations in Coffin–Siris syndrome are a cause of intellectual disability (0.5–1%), with various degrees of autism and agenesis of the corpus callosum (10%). Little is known regarding the cognitive and motor consequences of ARID1B mutations in humans and no link has been made between corpus callosum anomalies and visuospatial and neuromotor dysfunctions. We have investigated the visuospatial and neuromotor phenotype in eight patients with ARID1B mutations. A paramedian sagittal section of the brain MRI was selected, and corpus callosum was measured in anteroposterior length, genu and trunk width. Spearman’s rank order coefficients were used to explore correlations between visuospatial and social cognitive variables and dimensions of the corpus callosum. A significant correlation between genu width size and visual cognition was observed. Retrocerebellar cysts were associated with corpus callosum anomalies. Here, we show that corpus callosum anomalies caused in ARID1B mutations may be predictive of the visuospatial and motor phenotype in Coffin–Siris syndrome.

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

“…Sim et al 28 demonstrated the key role of ARID1B in brain development. Recent studies have revealed that ARID1B is the pathogenic gene of Coffin‐Siris syndrome type I 29–32 . The clinical manifestations of ARID1B mainly include special facial features (hairy, low ear position, wide nose, big mouth, etc.…”

The Evolutionary Conserved SWI/SNF Subunits ARID1A and ARID1B Are Key Modulators of Pluripotency and Cell-Fate Determination

“…Other characteristics of this disorder include respiratory infections, feeding issues, hearing loss, sparse scalp hair and hypermobility of joints (Vergano and Deardorff, 2014). Mutations in ARID1B have also been linked to Autism Spectrum Disorder (ASD), Intellectual Disabilities (ID), epilepsy and neuroblastoma (Vergano et al, 1993;Halgren et al, 2012;Hoyer et al, 2012;Santen et al, 2012;Vals et al, 2014;Yu et al, 2015;Ben-Salem et al, 2016;Sonmez et al, 2016;Jung et al, 2017;Lee et al, 2017;Shibutani et al, 2017;Yu et al, 2018;Demily et al, 2019;Filatova et al, 2019;Pranckeniene et al, 2019;Sekiguchi et al, 2019;van der Sluijs et al, 2019;Curcio et al, 2020;Fujita et al, 2020;Lian et al, 2020;Pascolini et al, 2020;Smith et al, 2020). ARID1B mutations can be associated with both syndromic and non-syndromic forms of ID (van der Sluijs et al, 2019).…”

A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder

“…One study reported brain MRI findings in three children with autism and ARID1B gene variants (Demily et al, 2019). The three participants reported by Demily et al (2019) were patients at the Necker Hospital and Hospices Civils de Lyon clinical genetics unit.…”

“…All participants had reported brain MRI abnormalities. White matter abnormalities included short and thick CC (Demily et al, 2019) and abnormalities in GM included 'temporal lobe dedifferentiation' (Demily et al, 2019, p.239). Demily et al (2019) also reported a cerebellar cyst in all three participants.…”

“…White matter abnormalities included short and thick CC (Demily et al, 2019) and abnormalities in GM included 'temporal lobe dedifferentiation' (Demily et al, 2019, p.239). Demily et al (2019) also reported a cerebellar cyst in all three participants. All participants were reported to have DD or ID and severe speech impairment.…”