Smith–Lemli–Opitz Syndrome

Cholesterol homeostasis is critical for normal growth and development, playing essential roles during embryogenesis, myelination, and brain development. Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive disorder due to an inborn error of post-squalene cholesterol biosynthesis, caused by mutations in DHCR7. A deficiency of DHCR7 activity experienced by individuals with SLOS often results in decreased levels of cholesterol and increased levels of 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) in plasma and tissues. Smith-Lemli-Opitz syndrome is characterized by a wide and variable spectrum of phenotypic abnormalities, including intellectual disability and multiple congenital malformations. Clinical features of behavior that are common in SLOS include intellectual disability, cognitive delay, sensory hyperreactivity, irritability, sleep difficulties, syndrome-specific motor movements, symptoms of autism spectrum disorder, language impairment, and self-injurious behavior. Cholesterol dysregulation impairs neuroplasticity, which may be a mechanism underlying some of the aforementioned abnormalities. This chapter describes recommended assessments, including diagnostic testing and behavioral analyses, of individuals suspected to have SLOS. It also defines signs and symptoms of common medical and psychiatric comorbidities and discusses current biological and psychosocial treatment options available to individuals with SLOS.