Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism

NCT05047354 | Recruiting

• 2 other identifiers: 10000487000487-CH
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Smith Lemli Opitz Syndrome; CHILD Syndrome; Lathosterolosis; Desmosterolosis

Keywords

7-dehydrocholesterol reductase; 7-dehydrocholesterol; cholesterol deficiency; Natural History

Outcome Measures

Primary Outcomes (2)

• The primary objective of this study is to determine laboratory or clinical outcome measures that could be used in future therapeutic trials.

  We will obtain data from patient evaluations that may be used as therapeutic targets in the fututre.

  ongoing

• The secondary objectives of these studies are to define comorbidities and mortality of the disease, to identify potential participants for future therapeutic trials and to evaluate possible laboratory outcome measures in carriers and suspected c...

  To describe in more detail long term manifestations of SLOS and disorders of cholesterol synthesis.

  ongoing

Study Arms (2)

1

Subjects with Smith-Lemli-Opitz syndrome

2

Subjects with Disorders of cholesterol synthesis and metabolism

Eligibility Criteria

• Age: 1 Day - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Male or female of any age with disorder of cholesterol metabolism. No geographic restrictions.

You may qualify if:

• 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.

You may not qualify if:

• Affected individuals who cannot travel to the NIH because of their medical condition will be excluded from on-site participation. They may participate in the telemedicine or in the biomaterials parts of the study.
• Affected individuals who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation will be excluded from on-site participation. They may participate in the telemedicine or in the
• biomaterials parts of the study.
• Carrier adults who are unable to or unwilling to provide any of the following samples: Blood, urine, skin biopsy sample or tissue derived from clinically indicated surgery or skin biopsy.
• Female participants who are pregnant will be excluded from evaluations requiring sedation, radiation and LP. Total blood draw volumes will be kept at a minimum or if anemia of pregnancy is known, no blood will be taken for research testing.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

• Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet. 2012 Nov 15;160C(4):250-62. doi: 10.1002/ajmg.c.31343. Epub 2012 Oct 11.

  PMID: 23059950 BACKGROUND

• Irons M, Elias ER, Salen G, Tint GS, Batta AK. Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome. Lancet. 1993 May 29;341(8857):1414. doi: 10.1016/0140-6736(93)90983-n. No abstract available.

  PMID: 7684480 BACKGROUND

• SMITH DW, LEMLI L, OPITZ JM. A NEWLY RECOGNIZED SYNDROME OF MULTIPLE CONGENITAL ANOMALIES. J Pediatr. 1964 Feb;64:210-7. doi: 10.1016/s0022-3476(64)80264-x. No abstract available.

  PMID: 14119520 BACKGROUND

• Selvaraman A, Rahhal S, Bianconi S, Furnary T, Porter FD. Assessing Postnatal Mortality in Smith-Lemli-Opitz Syndrome. Am J Med Genet A. 2025 Feb;197(2):e63875. doi: 10.1002/ajmg.a.63875. Epub 2024 Sep 13.

  PMID: 39271956 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Smith-Lemli-Opitz Syndrome; Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects; Lathosterolosis; Desmosterolosis

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Forbes D Porter, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derek M Alexander

CONTACT

(301) 827-0387; derek.alexander@nih.gov

Forbes D Porter, M.D.

CONTACT

(301) 435-4432; fdporter@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: September 17, 2021
• Study Start: June 23, 2021
• Primary Completion (Estimated): May 31, 2031
• Study Completion (Estimated): May 31, 2031
• Last Updated: March 2, 2026

Record last verified: 2026-02-26

Locations

US (1)