Neuroimaging, Behavior, and Biochemical Correlates in Smith-Lemli-Opitz Syndrome (SLOS)

Principal Investigator: Ryan Lee

SLOS is an autosomal recessive, multiple malformation syndrome of impaired cholesterol biosynthesis resulting in decreased cholesterol and elevated concentrations of abnormal sterols in tissues and blood (Irons, 1993). Cholesterol serves important biologic functions. It is a structural component of myelin and membrane lipid rafts, forms bile acids and neurosteroids, and facilitates hedgehog signaling (Porter, 2008; Fantini, 2009). Impairment of these basic cholesterol-dependent functions early in nervous system development is likely responsible for the SLOS clinical phenotype. There have been few case reports and one published study of neuroimaging in SLOS (Trasimeni, 1997; Oslejskova, 2008; Caruso, 2004). There are no studies applying advanced neuroimaging techniques such as diffusion tensor imaging (DTI), or correlating neuroimaging findings with behavioral and biochemical measures in SLOS. Although our understanding of the role of cholesterol in SLOS has advanced, many questions remain concerning brain structure and function, effectiveness of cholesterol replacement and simvastatin therapy, and the reliability of adjunct measures in clinical management. This study attempts to describe correlates between neuroimaging findings, behavior, and biochemistry in children with SLOS. If successful, this study may improve diagnostic and therapeutic management of subjects with SLOS, and benefit individuals with other neurodevelopmental disabilities.