Natural History Investigation Into Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism
Background: Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work.
Objective: To learn more about SLOS and related disorders and how these diseases affect participants and relatives.
Eligibility: People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed.
Design: Participants will be screened with a medical record review. Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body. Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history. Participation will last for several years.
‣ Males or females of any age with any one of the following:
⁃ Clinical, biochemical, or genetic diagnosis of Smith-Lemli-Opitz Syndrome OR
⁃ Clinical, biochemical, or genetic diagnosis of desmosterolosis, lathosterolosis, CHILD syndrome, X-linked dominant chondrodysplasia type2 or another inborn error of cholesterol synthesis OR
⁃ Clinical suspicion of an inborn error of cholesterol synthesis, metabolism or impaired cholesterol homeostasis. Clinical observations may include, but are not limited to lipid-laden macrophages, abnormal LDL, HDL, total cholesterol, triglycerides, abnormal lipid
‣ electrophoresis, lipid storage in other tissues. OR
• Biologic parents of affected individuals or known carriers based on previously done genetic testing who are willing and able to provide samples of any or all of the following: blood, urine, a skin biopsy, and/or tissue derived from clinically indicated surgery or autopsy.