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Study Description

Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol production by the body. It is caused by changes in the DHCR7 gene, which is the blueprint for an enzyme called 7-dehydrocholesterol- delta7-reductase. This enzyme is necessary for the production of cholesterol by all cells in the body. People with SLOS often have malformations of major organs, slow growth, feeding difficulties and intellectual disability or learning problems.

Because patients with SLOS cannot make enough cholesterol, it has been proposed that cholesterol supplementation (either with egg yolk or liquid suspensions of cholesterol) could help improve the symptoms of the disease. However, despite the widespread use of cholesterol supplementation, it is still not known whether it works or not. The study will try to provide an answer to this question by studying the disease and its progression while patients are receiving cholesterol.

The clinical features of SLOS are thought to be related to low cholesterol and buildup of toxic cholesterol precursors (substances from which cholesterol is formed). But how exactly low cholesterol and toxic precursors contribute to the disease is poorly understood. This knowledge is critically important because it should help discover new therapeutic targets and develop treatments of the disease in the long run. The study will try to fill this gap with a comprehensive clinical and biochemical testing of the study participants over the course of several years.

Last, a limitation of previous SLOS research studies has been their low number of participants. This is understandable because SLOS is a rare diseases and few research groups are working on it. However, in order to fully understand the disease, researchers need to study as many patients as possible. This study is unique in that it is run by a network of several highly specialized clinical research sites across the country. Having several sites involved increases the researcher's ability to recruit and study large number of patients, and centralize patients' information in a comprehensive SLOS clinical registry. This registry will be key to identify markers for diagnostic testing, screening and measuring outcomes in future studies of treatment.

The purpose of this study is to learn as much as possible about Smith-Lemli-Opitz Syndrome (SLOS) by following a large group of affected children and adults over time. In this study, we will measure cholesterol and other similar chemicals in blood and urine, evaluate development and behavior, do limited medical evaluation, and carry out brain imaging studies.This study will help researchers:

  • learn more about what causes SLOS and how SLOS changes with age,
  • note differences in features of SLOS among those affected,
  • evaluate the effect of giving extra cholesterol in this condition, and
  • develop ways to evaluate whether treatments developed in the future will be helpful.

  • Study Design:
    • Prospective Longitudinal Cohort
  • Study Type:
    • Longitudinal
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Study Inclusion/Exclusion Criteria

Subjects will be of all ages and all health status (i.e. no inclusion/exclusion criteria except for confirmed diagnosis of SLOS for inclusion). SLOS patients too ill to travel to the study sites or to safely undergo the testing involved will also be necessarily excluded. Neonates, children, and institutionalized subjects may be included, since those are frequent characteristics of the study group.

Study History

♦ Study Activated April 14, 2011
♦ First Accrual April 17, 2011
♦ Last accrual: September 13, 2015
♦ Study closed to enrollment: October 2015
♦ Last DSMB review February 6, 2017

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Diseases/Traits Related to Study (MeSH terms)
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