DTI Findings Related to Communication Impairment in SLOS

Background:  Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis with a high prevalence of intellectual disability and frequently accompanied autistic behavior and communication deficits. Communication impairment in autism is associated with abnormal hemispheric lateralization and elevated mean diffusivity (MD) in the left superior longitudinal fasciculus (SLF). The relationship between DTI findings in language-associated brain regions and communication impairment in SLOS has not been studied.

Objectives:  The aim of this study is to characterize the relationship between DTI findings in language-associated brain regions of interest (ROI) and standardized communication test scores in individuals with SLOS. Outcome measures include MD, mean fractional anisotropy (mFA), and volume of 8 atlas-based ROI. A secondary objective is to report the lateralization indices (LI) of DTI outcome measures in language-associated brain regions.

Methods: Ten children (mean age 10.1 +/-5.5) with SLOS underwent brain imaging on a 3T MRI scanner. Atlas-based DTI data for the right and left inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG), and superior longitudinal fasciculus (SLF) were reported using DTI Studio. Communication was assessed with the Vineland Adaptive Behavior Scales (VABS), communication domain (VABS-CD) and the ADI-R, Communication Domain (ADI-R -CD). Laterality Index (LI) = (left −right)/[(left + right)], was calculated for volume and mFA for all four regions. Statistical analysis was performed with student’s T-test and Pearson’s correlation (r).

Results:  In SLOS, lower VABS-CD score is correlated with higher mFA in right SLF (r=-0.72, p=0.023) and left SLF (r=-0.77, p=0.01). Higher rate of communication abnormalities according to the ADI-R Communication Domain is correlated with mFA in left STG (r=0.807, p=0.022), and MD in right SLF (r=0.723, p=0.046). In terms of laterality index, higher rate of abnormalities, determined by a higher ADI-R-CD correlates with higher mFA LI in the STG (r=0.61, p=0.036) and SLF (r=0.60, p=0.038) and volume LI in the STG (r=-0.74, p=0.006).

Conclusions:  In SLOS, DTI abnormalities in language regions are associated with severity of communication impairment. Specifically, increased lateralization of mFA and volume in the STG is associated with greater severity of communication impairment. Further studies investigating communication impairment in SLOS may lead to a better understanding of the neurobiologic basis of autism and other neurodevelopmental disorders.