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Smith Lemli Opitz Syndrome

Synonyms of Smith Lemli Opitz Syndrome

  • DHCR7 abnormality
  • RSH Syndrome
  • SLOS
  • SLO syndrome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Smith-Lemli-Opitz syndrome (SLOS) is a variable genetic disorder that is characterized by slow growth before and after birth, small head (microcephaly), mild to moderate mental retardation and multiple birth defects including particular facial features, cleft palate, heart defects, fused second and third toes, extra fingers and toes and underdeveloped external genitals in males. The severity of SLOS varies greatly in affected individuals, even in the same family, and some have normal development and only minor birth defects. SLOS is caused by a deficiency in the enzyme 7-dehydrocholesterol reductase that results in an abnormality in cholesterol metabolism. SLOS is inherited as an autosomal recessive genetic disorder.


The symptoms of SLOS vary greatly in affected individuals but the pattern of abnormalities that is typical includes growth delay, microcephaly, extra fingers and toes, fused second and third toes, cleft palate, underdeveloped external genitals in males and mental retardation.

Characteristic facial features associated with SLOS include drooping eyelids, fold in the inner corners of the eyes, fine wrinkles of the skin of the upper and lower eyelids, nostrils that are turned forward, long upper lip, inverted V shape of the upper lip, small jaw and large external ears. Abnormal gums are sometimes present and a variety of vision abnormalities, including cataracts, are seen in some affected individuals.

Occasional findings include seizures, heart defects, low muscle tone (hypotonia) in young children, a narrowing in the distal opening of the stomach (pyloric stenosis) and bowel obstruction. Many individuals with SLOS have an unusual sensitivity to light (photosensitivity).


SLOS is caused by a deficiency of the enzyme 7-dehydrocholesterol reductase. The enzyme deficiency occurs as the result of an abnormal DHCR7 gene inherited from each parent.

SLOS is an autosomal recessive genetic disorder. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

For the US the birth prevalence of SLOS has been estimated to be approximately 1 in 20,000 to 60,000 live births. The predicted prevalence based on newborn screening for gene carriers is estimated to be 1 in 1,590 to 13,500 and this discrepancy may be due to the fact that many fetuses with SLOS are stillborn. This condition occurs equally in males and females but females are often not diagnosed because genital abnormalities are missed. SLOS occurs more often in individuals of European ancestry.

Related Disorders


Standard Therapies

The diagnosis of SLOS is based on physical findings and detection of an elevated concentration of 7-dehydrocholesterol (7-DHC) in blood serum or an elevated 7-dehydrocholesterol:cholesterol ratio. Molecular genetic testing for mutations in the DHCR7 gene is available and is mainly used for carrier testing and prenatal diagnosis.

Medical treatment for SLOS is based on the specific problems that are present in the affected child. It is important that the child be evaluated for the range of conditions associated with SLOS including eye, heart, musculoskeletal, genitourinary and gastrointestinal disorders and that a physician familiar with SLOS oversees the care. Severely affected individuals may require surgery to correct cleft palate, heart defects and genital anomalies. Cholesterol supplementation (one or two egg yolks), sometimes in combination with bile acids, appears to improve growth and reduce photosensitivity in individuals with SLOS with no harmful side effects.

Genetic counseling is recommended for the parents of an affected child.

Investigational Therapies

Simvastatin has been successful in reducing cholesterol levels in individuals with SLOS but must be used with caution because of the possible risk of liver damage.

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:

Smith Lemli Opitz Syndrome Resources



Opitz JM. Smith-Lemli-Opitz Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:253.

Azurdia RM, Anstey AV, Rhodes LE. Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome. Br J Dermatol 2001;144:143-5.

Irons M, Elias ER Abuelo D, et al. Treatment of Smith-Lemli-Opitz syndrome:results of a multicenter trial. Am J Med Genet 1997;68:311-4.

Jira PE Wevers RA de Jong J, et al. Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome. J Lipid Res 2000;41:1339_46.

Kelly RI, Hennekam RCM. The Smith-Lemli-Opitz syndrome. J Med Genet 2000;37:321-335.

Linck LM, Lin DS, Flavell D, et al. Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome. Am J Med Genet 2000;93:363-365.

Nwokoro NA and Mulvill JJ. Cholesterol and bile acid replacement therapy in children and adults with Smith-Lemli-Opitz (SLO/RSH) syndrome. Am J Med Genet 1997;68:315-21.

Porter FD. RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome syndrome due to an inborn error of cholesterol biosynthesis. Mol Genet Metab 2000:71:163-74.

Starck L, Lovgran-Sandblom A, Bjorkhem I. Simvastatin treatment in the SLO syndrome: a safe approach? Am J Med Genet 2002:113:183-9.

Cunniff CM. (Updated 2/11/04) Smith-Lemli-Opitz Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource database online). Copyright, University of Washington, Seattle. 1997-2006. Available at Accessed 1/06.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD. The Johns Hopkins University; Entry No. 270400; Last Update 3/3/05.

eMedicine-Smith-Lemli-Opitz Syndrome: Article by Robert D Steiner, MD

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2007/07/23 00:00:00 GMT+0

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