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Genetics Home Reference: your guide to understanding genetic conditions
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Smith-Lemli-Opitz syndrome

Reviewed July 2007

What is Smith-Lemli-Opitz syndrome?

Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small head size (microcephaly), intellectual disability or learning problems, and behavioral problems. Many affected children have the characteristic features of autism, a developmental condition that affects communication and social interaction. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly).

The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual disability and major physical abnormalities.

How common is Smith-Lemli-Opitz syndrome?

Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 60,000 newborns. This condition is most common in Caucasians (whites) of European ancestry, particularly people from Central European countries such as Slovakia and the Czech Republic. It is very rare among African and Asian populations.

What genes are related to Smith-Lemli-Opitz syndrome?

Mutations in the DHCR7 gene cause Smith-Lemli-Opitz syndrome.

The DHCR7 gene provides instructions for making an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the production of cholesterol. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). Cholesterol is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.

Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood, nervous system, and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome.

Related Gene(s)

Changes in this gene are associated with Smith-Lemli-Opitz syndrome.

  • DHCR7

How do people inherit Smith-Lemli-Opitz syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Smith-Lemli-Opitz syndrome?

These resources address the diagnosis or management of Smith-Lemli-Opitz syndrome and may include treatment providers.

  • Gene Review: Smith-Lemli-Opitz Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1143)
  • Genetic Testing Registry: Smith-Lemli-Opitz syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0175694)

You might also find information on the diagnosis or management of Smith-Lemli-Opitz syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Smith-Lemli-Opitz syndrome?

You may find the following resources about Smith-Lemli-Opitz syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Smith-Lemli-Opitz syndrome?

  • 7-Dehydrocholesterol reductase deficiency
  • RSH Syndrome
  • SLOS
  • SLO syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Smith-Lemli-Opitz syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Smith-Lemli-Opitz syndrome?

acids ; autism ; autosomal ; autosomal recessive ; cell ; cholesterol ; deficiency ; digestive ; disability ; egg ; embryonic ; enzyme ; gastrointestinal ; gene ; genitalia ; hypotonia ; inherited ; microcephaly ; muscle tone ; nervous system ; polydactyly ; recessive ; syndactyly ; syndrome ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Smith-Lemli-Opitz Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1143)
  • Jira PE, Waterham HR, Wanders RJ, Smeitink JA, Sengers RC, Wevers RA. Smith-Lemli-Opitz syndrome and the DHCR7 gene. Ann Hum Genet. 2003 May;67(Pt 3):269-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12914579?dopt=Abstract)
  • Nowaczyk MJ, Waye JS, Douketis JD. DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients? Am J Med Genet A. 2006 Oct 1;140(19):2057-62. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16906538?dopt=Abstract)
  • Nowaczyk MJ, Waye JS. The Smith-Lemli-Opitz syndrome: a novel metabolic way of understanding developmental biology, embryogenesis, and dysmorphology. Clin Genet. 2001 Jun;59(6):375-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11453964?dopt=Abstract)
  • Porter FD. RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis. Mol Genet Metab. 2000 Sep-Oct;71(1-2):163-74. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11001807?dopt=Abstract)
  • Sikora DM, Pettit-Kekel K, Penfield J, Merkens LS, Steiner RD. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2006 Jul 15;140(14):1511-8. (http://www.ncbi.nlm.nih.gov/pubmed/16761297?dopt=Abstract)
  • Yu H, Patel SB. Recent insights into the Smith-Lemli-Opitz syndrome. Clin Genet. 2005 Nov;68(5):383-91. Review. Erratum in: Clin Genet. 2005 Dec;68(6):570. (http://www.ncbi.nlm.nih.gov/pubmed/16207203?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2007
Published: September 15, 2014