Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol synthesis, or production. It
is caused by mutations in the DHCR7 gene which encodes for 7-dehydrocholesterol-
Δ7-reductase, an enzyme necessary for the production of cholesterol in the body. Affected
individuals exhibit multiple malformations and mental retardation. The features of SLOS are
thought to be primarily related to cholesterol deficiency and accumulation of cholesterol
precursors. However, the clinical phenotype is not well characterized, the biochemical
pathogenesis is incompletely understood, and there is no proven therapy for this devastating
condition. Thus our primary objective is to better define the clinical and biochemical
phenotypes of the disease using a natural history study design. The study will contribute to
creating a comprehensive SLOS patient registry, identify biomarkers that can be used for
diagnostic testing, screening and outcome measures in future therapeutic trials. All
patients with SLOS receive dietary cholesterol supplementation with the hope that
cholesterol supplementation will improve the clinical manifestation of the disease. However,
there is no evidence supporting a clinical benefit of cholesterol supplementation. Thus a
secondary objective of the study is to determine if cholesterol intake correlates with
changes in whole body cholesterol homeostasis and clinical end-points.

Inclusion Criteria:

- Confirmed diagnosis of Smith-Lemli-Opitz Syndrome (SLOS)

- Males and females of all ages

- Willing and able to travel to OHSU or another STAIR site

Exclusion Criteria:

- Subject does not have Smith-Lemli-Opitz Syndrome (SLOS)