The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome

Am J Med Genet A. 2006 Jul 15;140(14):1511-8. doi: 10.1002/ajmg.a.31294.


Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive condition caused by a defect in cholesterol synthesis. Affected children often have malformations and mental retardation. Autistic behaviors also are evident. The purpose of the present study was to determine the prevalence of autism spectrum disorders (ASDs) in children with SLOS. Fourteen children, 3-16 years old, were evaluated using three different methods to document autistic symptoms: (a) parent interview, (b) direct observation, and (c) a behavior checklist. Blood sterols were also measured at regular intervals. Each subject was determined to have Autistic Disorder, Pervasive Developmental Disorder, not otherwise specified (PDD NOS), or no diagnosis on the autism spectrum, based on DSM-IV criteria. Correlations among variables were calculated, and blood sterol levels were compared between diagnostic groups. Approximately three-fourths of the children with SLOS (71-86% depending on the evaluation method) had an ASD, about 50% diagnosed with Autistic Disorder and the rest with PDD NOS. The children's baseline cholesterol, 7-dehydrocholesterol (7-DHC), and 8-dehydrocholesterol (8-DHC) levels, and cholesterol levels following supplementation did not correlate with the presence or severity of autistic symptoms. These results suggest that most children with SLOS have some variant of autism. SLOS appears to have the most consistent relationship with autism of any single gene disorder. Therefore, a link between cholesterol metabolism and autism is suggested. With further study, these findings, together with knowledge of the genetic and biochemical defects in SLOS, will likely provide valuable insights into the causes of autism in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autistic Disorder / complications*
  • Autistic Disorder / diagnosis
  • Autistic Disorder / genetics*
  • Autistic Disorder / metabolism
  • Child
  • Child, Preschool
  • Cholesterol / biosynthesis
  • Female
  • Genes, Recessive
  • Humans
  • Male
  • Smith-Lemli-Opitz Syndrome / genetics*
  • Smith-Lemli-Opitz Syndrome / metabolism


  • Cholesterol