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Challenging Behavior in Smith-Lemli-Opitz Syndrome: Initial Test of Biobehavioral Influences

Freeman, Kurt A. PhD, ABPP*,†; Eagle, Rose PhD*; Merkens, Louise S. PhD; Sikora, Darryn PhD*,†; Pettit-Kekel, Kersti OTR/L†,‡; Nguyen-Driver, Mina PsyD*,†; Steiner, Robert D. MD§,¶

Cognitive and Behavioral Neurology: March 2013 - Volume 26 - Issue 1 - p 23–29
doi: 10.1097/WNN.0b013e31828bf6d5
Original Studies

Objective: To study challenging behavior (destruction, aggression, self-injury, stereotypy) in children with Smith-Lemli-Opitz syndrome (SLOS) using a biobehavioral model that helps distinguish biological from socially mediated variables influencing the behavior.

Background: SLOS is an autosomal-recessive syndrome of multiple malformations and intellectual disability resulting from a genetic error in cholesterol synthesis in all cells and tissues, including brain. The exact cause of the challenging behavior in SLOS is unclear, but defective brain cholesterol synthesis may contribute. Because the precise genetic and biochemical etiology of SLOS is known, this disorder is a good model for studying biological causes of challenging behavior.

Method: In a preliminary application of a biobehavioral model, we studied the association between cholesterol levels (as a biochemical indicator of disease severity) and behavior subtype (“biological” vs “learned”) in 13 children with SLOS. Parents completed a questionnaire that categorized challenging behavior as influenced primarily by social or nonsocial (thus, presumably biological) factors.

Results: The severity of the cholesterol synthesis defect correlated significantly with behavior subtype classification for 1 of 2 challenging behaviors. Greater severity of the cholesterol synthesis defect was associated with behavior being classified as primarily influenced by biological factors.

Conclusion: The interplay between challenging behavior and defective cholesterol synthesis in SLOS may help explain biological influences on the behavior. Our findings have implications for research on the effectiveness of behavioral and medical treatments for behavioral difficulties in SLOS and other neurodevelopmental disorders.

*Division of Psychology, Institute on Development & Disability

Department of Pediatrics

Division of Occupational Therapy, Institute on Development & Disability

§Department of Pediatrics

Department of Molecular Medical Genetics, Oregon Clinical and Translational Research Institute, Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, Oregon

Supported by National Institutes of Health grants R01 HL073980 to R.D.S. and M01 RR000334 to Oregon Health & Science University. Publication supported in part by the Oregon Clinical and Translational Research Institute, grant UL1 RR024140 from the National Center for Research Resources.

The authors declare no conflicts of interest.

Reprints: Kurt A. Freeman, PhD, ABPP, Institute on Development & Disability, Oregon Health & Science University, 707 SW Gaines, Portland, OR 97239 (e-mail:

Received February 22, 2012

Accepted October 23, 2012

© 2013 Lippincott Williams & Wilkins, Inc.