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

Status:	Recruiting
Healthy:	No
Age Range:	Any - 85
Updated:	4/2/2016
Start Date:	January 2011
Contact:	Sharon Butcher, RN, MSN, CPNP
Email:	butcher@ohsu.edu
Phone:	503-494-6524

Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation

The purpose of this study is to learn about Smith-Lemli-Opitz Syndrome (SLOS). SLOS is an
inherited condition that is caused by the body not making an enzyme as it should. The body
needs the enzyme to help make cholesterol. SLOS can cause many health problems including
slow growth and development, eating disorders, sleep disorders, behavior disorders, and eye
diseases. Severe SLOS leads to birth defects and mental retardation and in many cases early
death. The investigators plan to measure cholesterol and other sterol levels, perform
clinical observations, whole body testing and imaging (brain MRIs), to learn more about the
disease and its progression, differences in the clinical features among individuals with
SLOS, and look at the effect of cholesterol supplementation in this condition.

The study is an interventional study to characterize disease progression and correlations
between clinical, biochemical and physiological features of the disease. The main hypothesis
is that dietary cholesterol supplementation does not improve features of SLOS related to the
brain (e.g. IQ, behavior).

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)

We found this trial at

sites

Pdgen, Nichd, Nih, Dhhs

Bethesda, Maryland 20892

from

Bethesda, MD