Cognitive and behavioral aspects of Smith–Lemli–Opitz syndrome

Abstract

The brain's high concentrations of cholesterol make it especially vulnerable to the cholesterol biosynthetic defect that characterizes Smith-Lemli-Opitz syndrome (SLOS). An attempt to characterize the cognitive and behavioral phenotype of SLOS has identified increased rates of intellectual disability, language and motor developmental delay, repeated self-injury behaviors, sensory hyperreactivity, hyperactivity, affect dysregulation, and sleep disturbances. Some research has suggested that carriers of the gene mutation that results in SLOS display increased risk of suicidal behavior. Cholesterol dysregulation impairs neuroplasticity, which may be a mechanism underlying some of the mentioned abnormalities. Discrete positive effects have been reported with the use of cholesterol supplementation in the treatment of SLOS. Research has been limited by the small number of subjects available, and a limited understanding of lipid metabolism in the brain. Hopefully future research will help clarify the role that cholesterol plays in cognitive and behavioral abnormalities like the ones associated with SLOS. This would accelerate the development of treatments for SLOS, and perhaps also further understanding of non-syndromic psychiatric disorders such as autism and attention deficit hyperactivity disorder.

Smith-Lemli-Opitz-syndrome: How different is the anesthetic technique?

“…Intellectual impairment along with aggression, self-injurious behavior and hyperactivity may be seen in these patients. [10] Our patient was irritable and crying, but did not show aggressive behavior. EMLA cream would be useful in securing an IV access in these patients with risk of difficult airway.…”

Environmental Influences on Biochemistry in Autism Spectrum Disorder

“…Autism is a common comorbidity for Smith-Lemli Opitz Syndrome (SLOS). SLOS is a genetic syndrome characterized by cholesterol dysregulation initiated by deficient activity of 7-dehydrocholesterol reductase [22]. The presence of autism in SLOS supports the idea that lipid associated pathways may be disrupted in ASD [17,23].…”

The Potential for Proteomics in Understanding Neurodevelopmental Disorders

“…Total or partial deficiency of Dhcr7 causes SLOS [69]. As mentioned, several developmental disorders are associated with SLOS, including incomplete myelination, and mental retardation [70] as well as autism [64][65][66][67]. Tissue cholesterol and total sterol levels are substantially depleted, and 7-dehydrocholesterol levels increase SLOS and the Dhcr7 gene.…”

“…Smith-Lemli-Opitz Syndrome (SLOS) is an inborn decrease of cholesterol synthesis associated with ASD symptoms [64][65][66][67]. Although this may be conceived of as a disorder of metabolism, rather than a neurodevelopmental disorder, autism and mental retardation are highly prevalent in SLOS.…”