Children with SLOS Demonstrate a Different Pattern Brain Microstructure Than Autism and Rett Syndrome

Background: Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis that results in multiple congenital malformations, intellectual disability and autistic behavior. Diffusion tensor imaging (DTI) studies in children with autism show increased mean fractional anisotropy (mFA) in infancy, followed by a decrease in mFA between ages 2.5 to 9 years, when compared with typically developing (TD) controls. A similar pattern has been described in individuals with Rett syndrome. There are no published DTI studies in SLOS.  

Objectives: The following study aims to compare the DTI findings in SLOS with TD controls. Outcome measures include mFA, MD, and volume for 40 atlas-based ROI previously described in studies of individuals with autism and Rett syndrome. A secondary aim is to compare the DTI findings in SLOS with those reported in autism and Rett syndrome.

Methods:  Ten children (mean= 10.1 years +/-5.5) with SLOS, and 27 TD controls (mean=9.7 years +/-7.5) received 3T MRI scans. Statistical analyses applied student’s T-test. SLOS children underwent ASD testing with ADI-R and ADOS by expert clinicians who emitted a clinical judgment using DSM-IV criteria.

Results:  Individuals with SLOS showed higher mFA, decreased volume, and decreased MD compared to controls for the majority of ROI studied (30/40, 75%). These results contrast with the pattern of microstructural findings in children with autism and Rett syndrome. Pending analysis within SLOS group will compare microstructural diffusion characteristics between autistic and non-autistic SLOS children.

Conclusions: The pattern of DTI findings in SLOS differ from those reported in autism, Rett syndrome and controls. These findings suggest that while autistic symptoms are present in these three neurodevelopmental disorders, a unique microstructural substrate in SLOS may be underlying the autistic behaviors described in the phenotype. Further studies are required to reveal the neurobiologic causes of autistic behavior in SLOS.