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Smith-Lemli-Opitz Syndrome

  • Author: Robert D Steiner, MD; Chief Editor: Luis O Rohena, MD  more...
Updated: Apr 01, 2015


Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomalies (MCA)/mental retardation (MR) syndrome caused by a defect in cholesterol synthesis. Smith-Lemli-Opitz syndrome is an autosomal recessive genetic condition caused by deficiency of the enzyme 3 beta-hydroxysterol-delta 7-reductase (7-dehydrocholesterol-delta 7-reductase [DHCR7] EC, the final enzyme in the sterol synthetic pathway that converts 7-dehydrocholesterol (7DHC) to cholesterol.

Affected individuals usually have low plasma cholesterol levels and invariably have elevated levels of cholesterol precursors, including 7DHC. Severely affected individuals (those with the condition formerly referred to as Smith-Lemli-Opitz syndrome type II) have multiple congenital malformations and are often miscarried or stillborn or die in the first weeks of life. Dysmorphic facial features, microcephaly, second-toe and third-toe syndactyly, other malformations, and MR are typical. Mildly affected individuals may have only subtle dysmorphic features and learning and behavioral disabilities.

See the image below.

Child with Smith-Lemli-Opitz syndrome. Child with Smith-Lemli-Opitz syndrome.


The classic paradigm for the pathogenesis of an inborn error of metabolism includes the accumulation of a toxic precursor and/or deficiency of an essential product as a result of an enzyme deficiency. In the case of Smith-Lemli-Opitz syndrome, the precursor 7DHC is potentially toxic in large concentrations, and cholesterol deficiency is almost certainly detrimental.

Smith, Lemli, and Opitz initially described Smith-Lemli-Opitz syndrome as a genetic MCA/MR syndrome in 1964.[1] They named the condition RSH after the first initial of the last names of the first 3 patients ascertained.[2] The clinical characteristics of Smith-Lemli-Opitz syndrome have been well established over the past 4 decades.

The etiology of Smith-Lemli-Opitz syndrome was unknown until 1993, when Irons et al discovered that patients with Smith-Lemli-Opitz syndrome had low plasma cholesterol levels and accumulated sterol precursors such as 7DHC.[3] A deficiency of the microsomal enzyme DHCR7, which reduces the 7-8 double bond of 7DHC to form cholesterol in the final step of the cholesterol synthetic pathway, was hypothesized and later proven to cause Smith-Lemli-Opitz syndrome. Mutations in the DHCR7 gene are responsible for Smith-Lemli-Opitz syndrome. Therefore, Smith-Lemli-Opitz syndrome can now be considered a classic inborn error of metabolism.

Currently, the reason defects in cholesterol synthesis cause congenital malformations is not known. Several disparate lines of research have led to recent understanding of the critical and somewhat unexpected role of cholesterol in early human development. Cholesterol is important in cell membranes, serves as the precursor for steroid hormones and bile acids, and is a major component in myelin. Cholesterol is covalently bound to the embryonic signaling protein sonic hedgehog (Shh) in a necessary step of the autoprocessing of the precursor to active form, occurring about age gestational day 0-7 in humans.

Shh plays a critical role in several embryologic fields relevant to Smith-Lemli-Opitz syndrome (eg, brain, face, heart, limbs). Therefore, cholesterol is an essential triggering agent in the early developmental program of the human. Because 7DHC can also activate Shh, cholesterol deficiency that leads to decreased activation of Shh is probably not the sole explanation for congenital malformations in this syndrome.

Abnormalities in the Shh-patched signaling cascade presumably play a role. Membrane instability and dysmyelination from cholesterol deficiency and accumulation of 7DHC and other potentially toxic cholesterol precursors are also likely to contribute to the Smith-Lemli-Opitz syndrome phenotype.

Increased isoprenoids were reported in Smith-Lemli-Opitz syndrome, but the role these nonsterol isoprenoids play in the pathophysiology of this disorder is unclear.[4]

A study by Merkens et al indicated that high 7DHC plasma levels correlate with feeding difficulties in patients with Smith-Lemli-Opitz syndrome. In the report, which involved 26 patients (aged 0.4-19 years) with the syndrome, the investigators found that patients with a plasma level of more than 0.24 mmol/L or a cholesterol concentration of less than 1.95 mmol/L were more likely to require use of a gastrostomy tube.[5]

A study by Sparks et al found reduced levels of the neurotransmitter metabolites 5-hydroxyindoleacetic acid (from serotonin) and homovanillic acid (from dopamine) in the cerebrospinal fluid of patients with Smith-Lemli-Opitz syndrome. The investigators suggested that this may result from a sterol-associated defect in synaptic vesicle development.[6]




United States

Prevalence of Smith-Lemli-Opitz syndrome has been estimated to be 1 in 20,000-60,000 births among whites. Smith-Lemli-Opitz syndrome is also not uncommon in Hispanics. Its specific prevalence in different populations has not been precisely determined. The higher-than-expected prevalence of Smith-Lemli-Opitz syndrome suggests a heterozygote advantage.

Only one description of an African-American patient has been published, although no biochemical or molecular confirmation of Smith-Lemli-Opitz syndrome was available.[7] In a study of 150 biochemically diagnosed patients with Smith-Lemli-Opitz syndrome, only one individual was of African descent.[8] In 2000, Yu and colleagues did not detect the mutation among 121 Africans from Sierra Leone.[9] In 2001, Nowaczyk and colleagues reported an IVS8-1G>C (common Smith-Lemli-Opitz syndrome mutation) carrier frequency of 1.09% (17 per 1559 population) in Canadian whites and 0.79% (4 per 504 population) in Canadians of African descent; however, no African Canadian patients were identified.[10]

The results of Wright et al's 2003 study indicate an IVS8-1G>C carrier frequency of 0.73% (10 per 1378 population) in African Americans.[11] This predicts the prevalence of Smith-Lemli-Opitz syndrome due to IVS8-1G>C homozygosity to be 1 case per 75,061 persons in the African American population. Although the African American carrier frequency of the IVS8-1G>C allele was determined to be 0.73%, few African American patients with Smith-Lemli-Opitz syndrome have been identified.

Carrier frequency for Smith-Lemli-Opitz syndrome is approximately 1 in 30 persons of northern European descent, suggesting a disease frequency of 1 per 5000-18,000 people. The actual disease prevalence may be lower because of fetal losses.


Smith-Lemli-Opitz syndrome has been described in patients from the United States, many northern European countries, Japan, South America, and other countries. Smith-Lemli-Opitz syndrome appears to be uncommon in Japan. The frequency of Smith-Lemli-Opitz syndrome appears to be similar in northern Europe and the United States, but additional studies are needed to determine the frequency of Smith-Lemli-Opitz syndrome in other regions. The European origin of some of the major mutations found in Smith-Lemli-Opitz syndrome has been explored.[12]


Spontaneous abortion of fetuses with Smith-Lemli-Opitz syndrome is not unusual. Stillbirths have also been reported. Death from multiorgan system failure during the first weeks of life is typical in individuals with Smith-Lemli-Opitz syndrome type II. Cause of death can include pneumonia, lethal congenital heart defect, or hepatic failure. Survival is unlikely if the plasma cholesterol level is less than approximately 20 mg/dL as measured by gas chromatography, which is used because routine methods of cholesterol measurement include precursor sterols.

Congenital heart disease is not uncommon in Smith-Lemli-Opitz syndrome and can cause cyanosis or congestive heart failure. Pulmonary hypertension has been noted in at least one patient.[13] Vomiting, feeding difficulties, constipation, toxic megacolon, electrolyte disturbances, and failure to thrive are common and, in some cases, related to GI anomalies. Liver disease has been commonly described.[14] Visual loss may occur because of cataracts, optic nerve abnormalities, or other ophthalmologic problems,[15] and subclinical retinal abnormalities may be noted on electroretinography.[16] Cataracts may occur acutely in the postnatal period.[17] Hearing loss is fairly common.


See Frequency.


As an autosomal recessive genetic condition, Smith-Lemli-Opitz syndrome is equally prevalent among males and females.


Smith-Lemli-Opitz syndrome is a genetic condition that is present from conception, but signs may occasionally be so subtle that patients avoid detection until later childhood or even adulthood. Some have postulated that the mildest cases may completely escape detection in some instances. More commonly, Smith-Lemli-Opitz syndrome is suspected at birth or shortly thereafter because of birth defects.

Contributor Information and Disclosures

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Laura S Martin, MD, and Roderick F Hume, MD, to the writing and development of this article.

  1. Smith DW, Lemli L, Opitz JM. A newly recognized syndrome of multiple congenital anomalies. J Pediatr. 1964 Feb. 64:210-7. [Medline].

  2. Opitz JM. RSH (so-called Smith-Lemli-Opitz) syndrome. Curr Opin Pediatr. 1999 Aug. 11(4):353-62. [Medline].

  3. Irons M, Elias ER, Tint GS. Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient. Am J Med Genet. 1994 May 1. 50(4):347-52. [Medline].

  4. Pappu AS, Connor WE, Merkens LS, et al. Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli-Opitz syndrome: effects of dietary cholesterol. J Lipid Res. 2006 Dec. 47(12):2789-98. [Medline].

  5. Merkens MJ, Sinden NL, Brown CD, et al. Feeding impairments associated with plasma sterols in Smith-Lemli-Opitz syndrome. J Pediatr. 2014 Oct. 165(4):836-41.e1. [Medline]. [Full Text].

  6. Sparks SE, Wassif CA, Goodwin H, et al. Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome. J Inherit Metab Dis. 2014 May. 37(3):415-20. [Medline]. [Full Text].

  7. Hanissian AS, Summitt RL. Smith-Lemli-Opitz Syndrome in a Negro Child. J Pediatr. 1969 Feb. 74(2):303-5. [Medline].

  8. Kelley RI. A new face for an old syndrome [editorial]. Am J Med Genet. 1997 Jan 31. 68(3):251-6. [Medline].

  9. Yu H, Tint GS, Salen G, et al. Detection of a common mutation in the RSH or Smith-Lemli-Opitz syndrome by a PCR-RFLP assay: IVS8-G-->C is found in over sixty percent of US propositi. Am J Med Genet. 2000 Feb 14. 90(4):347-50. [Medline].

  10. Nowaczyk MJ, McCaughey D, Whelan DT, et al. Incidence of Smith-Lemli-Opitz syndrome in Ontario, Canada. Am J Med Genet. 2001 Jul 22. 102(1):18-20. [Medline].

  11. Wright BS, Nwokoro NA, Wassif CA, et al. Carrier frequency of the RSH/Smith-Lemli-Opitz IVS8-1G>C mutation inAfrican Americans. Am J Med Genet. 2003 Jul 1. 120A(1):139-41. [Medline].

  12. Witsch-Baumgartner M, Schwentner I, Gruber M, Benlian P, et al. Age and origin of major Smith-Lemli-Opitz syndrome (SLOS) mutations in European populations. J Med Genet. 2008 Apr. 45(4):200-9. [Medline].

  13. Katheria AC, Masliah E, Benirschke K, Jones KL, Kim JH. Idiopathic persistent pulmonary hypertension in an infant with Smith-Lemli-Opitz syndrome. Fetal Pediatr Pathol. 2010. 29(6):373-9. [Medline].

  14. Rossi M, Vajro P, Iorio R, et al. Characterization of liver involvement in defects of cholesterol biosynthesis: long-term follow-up and review. Am J Med Genet A. 2005 Jan 15. 132(2):144-51. [Medline].

  15. Atchaneeyasakul LO, Linck LM, Connor WE. Eye findings in 8 children and a spontaneously aborted fetus with RSH/Smith-Lemli-Opitz syndrome. Am J Med Genet. 1998 Dec 28. 80(5):501-5. [Medline].

  16. Garry D, Hansen RM, Moskowitz A, Elias ER, Irons M, Fulton AB. Cone ERG responses in patients with Smith-Lemli-Opitz Syndrome (SLOS). Doc Ophthalmol. 2010 Oct. 121(2):85-91. [Medline]. [Full Text].

  17. Goodwin H, Brooks BP, Porter FD. Acute postnatal cataract formation in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2008 Jan 15. 146A(2):208-11. [Medline].

  18. 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. [Medline].

  19. Lee RW, McGready J, Conley SK, Yanjanin NM, Nowaczyk MJ, Porter FD. Growth charts for individuals with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2012 Nov. 158A(11):2707-13. [Medline]. [Full Text].

  20. Oslejskova H, Horinova V, Sterba J, et al. Malignant intracranial germinoma in Smith-Lemli-Opitz syndrome: cholesterol homeostasis possibly connecting morphogenesis and cancer development. J Pediatr Hematol Oncol. 2008 Sep. 30(9):689-91. [Medline].

  21. Goodwin H, Brooks BP, Porter FD. Acute postnatal cataract formation in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2008 Jan 15. 146A(2):208-11. [Medline].

  22. Waterham HR, Hennekam RC. Mutational spectrum of Smith-Lemli-Opitz syndrome. Am J Med Genet C Semin Med Genet. 2012 Nov 15. 160C(4):263-84. [Medline].

  23. Liu W, Xu L, Lamberson CR, Merkens LS, Steiner RD, Elias ER, et al. Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients. J Lipid Res. 2013 Jan. 54(1):244-53. [Medline]. [Full Text].

  24. Shackleton CH, Roitman E, Kratz LE. Equine type estrogens produced by a pregnant woman carrying a Smith- Lemli-Opitz syndrome fetus. J Clin Endocrinol Metab. 1999 Mar. 84(3):1157-9. [Medline].

  25. Ness GC, Lopez D, Borrego O. Increased expression of low-density lipoprotein receptors in a Smith- Lemli-Opitz infant with elevated bilirubin levels. Am J Med Genet. 1997 Jan 31. 68(3):294-9. [Medline].

  26. Svoboda MD, Christie JM, Eroglu Y, Freeman KA, Steiner RD. Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders. Am J Med Genet C Semin Med Genet. 2012 Nov 15. 160C(4):285-94. [Medline].

  27. FDA. FDA approves Cholbam to treat rare bile acid synthesis disorders. US Food and Drug Administration. Available at Accessed: Apr 1 2015.

  28. Cholbam (cholic acid) [package insert]. Baltimore, MD: Asklepion Pharmaceuticals LLC. Mar 2015. Available at [Full Text].

  29. Lowes R. Cholbam Approved for Rare Metabolic Disorders. Medscape Medical News. Mar 17 2015. [Full Text].

  30. Tierney E, Conley SK, Goodwin H, Porter FD. Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2010 Jan. 152A(1):91-5. [Medline]. [Full Text].

  31. Irons MB, Nores J, Stewart TL. Antenatal therapy of Smith-Lemli-Opitz syndrome. Fetal Diagn Ther. 1999 May-Jun. 14(3):133-7. [Medline].

  32. Haas D, Garbade SF, Vohwinkel C, et al. Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). J Inherit Metab Dis. 2007 Jun. 30(3):375-87. [Medline].

  33. Haas D, Garbade SF, Vohwinkel C, et al. Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). J Inherit Metab Dis. 2007 Jun. 30(3):375-87. [Medline].

  34. Nowaczyk MJ, Siu VM, Krakowiak PA, et al. Adrenal insufficiency and hypertension in a newborn infant with Smith-Lemli-Opitz syndrome. Am J Med Genet. 2001 Oct 15. 103(3):223-5. [Medline].

  35. Pauli RM, Williams MS, Josephson KD. Smith-Lemli-Opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome. Am J Med Genet. 1997 Jan 31. 68(3):260-2. [Medline].

  36. Abuelo DN, Tint GS, Kelley R. Prenatal detection of the cholesterol biosynthetic defect in the Smith- Lemli-Opitz syndrome by the analysis of amniotic fluid sterols. Am J Med Genet. 1995 Apr 10. 56(3):281-5. [Medline].

  37. Angle B, Tint GS, Yacoub OA. Atypical case of Smith-Lemli-Opitz syndrome: implications for diagnosis. Am J Med Genet. 1998 Dec 4. 80(4):322-6. [Medline].

  38. Azurdia RM, Anstey AV, Rhodes LE. Cholesterol supplementation objectively reduces photosensitivity in theSmith-Lemli-Opitz syndrome. Br J Dermatol. 2001 Jan. 144(1):143-5. [Medline].

  39. Battaile KP, Maslen CL, Wassif CA, et al. A simple PCR-based assay allows detection of a common mutation, IVS8-1G- ->C, in DHCR7 in Smith-Lemli-Opitz syndrome. Genet Test. 1999. 3(4):361-3. [Medline].

  40. Battaile KP, Steiner RD. Smith-Lemli-Opitz syndrome: the first malformation syndrome associated with defective cholesterol synthesis [In Process Citation]. Mol Genet Metab. 2000 Sep-Oct. 71(1-2):154-62. [Medline].

  41. Battaille KP, Battaile BC, Merkens LS. Carrier frequency of the common mutation IVS8-1 G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome. Mol Gen Metab. 2001. 72:67-71. [Full Text].

  42. Bradley LA, Palomaki GE, Knight GJ. Levels of unconjugated estriol and other maternal serum markers in pregnancies with Smith-Lemli-Opitz (RSH) syndrome fetuses [letter]. Am J Med Genet. 1999 Feb 12. 82(4):355-8. [Medline].

  43. Bronshtein M, Riechler A, Zimmer EZ. Prenatal sonographic signs of possible fetal genital anomalies. Prenat Diagn. 1995 Mar. 15(3):215-9. [Medline].

  44. Canick JA, Abuelo DN, Bradley LA. Maternal serum marker levels in two pregnancies affected with Smith- Lemli-Opitz syndrome [letter]. Prenat Diagn. 1997 Feb. 17(2):187-9. [Medline].

  45. Chambers CM, McLean MP, Ness GC. Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous injection of lipoprotein cholesterol. Am J Med Genet. 1997 Jan 31. 68(3):322-7. [Medline].

  46. Cunniff C, Kratz LE, Moser A. Clinical and biochemical spectrum of patients with RSH/Smith-Lemli- Opitz syndrome and abnormal cholesterol metabolism. Am J Med Genet. 1997 Jan 31. 68(3):263-9. [Medline].

  47. Dallaire L, Mitchell G, Giguere R. Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7-dehydrocholesterol in amniotic fluid. Prenat Diagn. 1995 Sep. 15(9):855-8. [Medline].

  48. Dehart DB, Lanoue L, Tint GS. Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz syndrome. Am J Med Genet. 1997 Jan 31. 68(3):328-37. [Medline].

  49. Elias ER, Hansen RM, Irons M, et al. Rod photoreceptor responses in children with smith-lemli-opitz syndrome. Arch Ophthalmol. 2003 Dec. 121(12):1738-43. [Medline].

  50. Elias ER, Irons MB, Hurley AD. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet. 1997 Jan 31. 68(3):305-10. [Medline].

  51. Fitzky BU, Witsch-Baumgartner M, Erdel M. Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci U S A. 1998 Jul 7. 95(14):8181-6. [Medline].

  52. Ginat S, Battaile KP, Battaile BC. Lowered DHCR7 activity measured by ergosterol conversion in multiple cell types in Smith-Lemli-Opitz syndrome. Mol Genet Metab. 2004 Sep-Oct. 83(1-2):175-83. [Medline].

  53. Ginat S, Maslen CL, Connor WE. Smith-Lemli-Opitz syndrome: a multiple malformation/mental retardation syndrome caused by defective cholesterol synthesis. The Endocrinologist. 2000. 10:300-314.

  54. Herz J, Willnow TE, Farese RV Jr. Cholesterol, hedgehog and embryogenesis [letter]. Nat Genet. 1997 Feb. 15(2):123-4. [Medline].

  55. Honda A, Batta AK, Salen G. Screening for abnormal cholesterol biosynthesis in the Smith-Lemli- Opitz syndrome: rapid determination of plasma 7-dehydrocholesterol by ultraviolet spectrometry. Am J Med Genet. 1997 Jan 31. 68(3):288-93. [Medline].

  56. Honda A, Tint GS, Salen G. Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts: diagnosis of a biochemically atypical case of the syndrome. Am J Med Genet. 1997 Jan 31. 68(3):282-7. [Medline].

  57. Honda M, Tint GS, Shefer S. Accurate detection of Smith-Lemli-Opitz syndrome carriers by measurement of the rate of reduction of the ergosterol C-7 double bond in cultured skin fibroblasts. J Inherit Metab Dis. 1998 Oct. 21(7):761-8. [Medline].

  58. Hyett JA, Clayton PT, Moscoso G. Increased first trimester nuchal translucency as a prenatal manifestation of Smith-Lemli-Opitz syndrome. Am J Med Genet. 1995 Sep 25. 58(4):374-6. [Medline].

  59. Irons M, Elias ER, Abuelo D. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet. 1997 Jan 31. 68(3):311-4. [Medline].

  60. Irons M, Elias ER, Salen G. Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome [letter]. Lancet. 1993 May 29. 341(8857):1414. [Medline].

  61. Irons MB, Tint GS. Prenatal diagnosis of Smith-Lemli-Opitz syndrome. Prenat Diagn. 1998 Apr. 18(4):369-72. [Medline].

  62. Jira P, Wevers R, de Jong J. New treatment strategy for Smith-Lemli-Opitz syndrome [letter]. Lancet. 1997 Apr 26. 349(9060):1222. [Medline].

  63. Jira PE, Wevers RA, de Jong J. Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome. J Lipid Res. 2000 Aug. 41(8):1339-46. [Medline].

  64. Johnson DW, ten Brink HJ, Jakobs C. A rapid screening procedure for cholesterol and dehydrocholesterol by electrospray ionization tandem mass spectrometry. J Lipid Res. 2001 Oct. 42(10):1699-705. [Medline].

  65. Johnson JA, Aughton DJ, Comstock CH. Prenatal diagnosis of Smith-Lemli-Opitz syndrome, type II. Am J Med Genet. 1994 Jan 15. 49(2):240-3. [Medline].

  66. Kelley RI. RSH/Smith-Lemli-Opitz syndrome: mutations and metabolic morphogenesis. Am J Hum Genet. 1998 Aug. 63(2):322-6. [Medline].

  67. Krakowiak PA, Nwokoro NA, Wassif CA. Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping [In Process Citation]. Am J Med Genet. 2000 Sep 18. 94(3):214-27. [Medline].

  68. Lin DS, Steiner RD, Flavell DP. Intestinal absorption of cholesterol by patients with smith-lemli-opitz syndrome. Pediatr Res. 2005 Jun. 57(6):765-70. [Medline].

  69. Linck LM, Hayflick SJ, Lin DS, et al. Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol Delta(7)- reductase activity in chorionic villi. Prenat Diagn. 2000 Mar. 20(3):238-40. [Medline].

  70. Linck LM, Lin DS, Flavell D. Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome [In Process Citation]. Am J Med Genet. 2000 Aug 28. 93(5):360-5. [Medline].

  71. Lowry RB, Yong SL. Borderline normal intelligence in the Smith-Lemli-Opitz (RSH) syndrome. Am J Med Genet. 1980. 5(2):137-43. [Medline].

  72. McGaughran JM, Clayton PT, Mills KA. Prenatal diagnosis of Smith-Lemli-Opitz syndrome. Am J Med Genet. 1995 Apr 10. 56(3):269-71. [Medline].

  73. McKusick VA. OMIM Number:270400. Online Mendelian Inheritance in Man, OMIM. Available at Accessed: October 3, 1999.

  74. Merkens LS, Connor WE, Linck LM. Effects of dietary cholesterol on plasma lipoproteins in Smith-Lemli-Opitz syndrome. Pediatr Res. 2004 Nov. 56(5):726-32. [Medline].

  75. Mills K, Mandel H, Montemagno R. First trimester prenatal diagnosis of Smith-Lemli-Opitz syndrome (7- dehydrocholesterol reductase deficiency). Pediatr Res. 1996 May. 39(5):816-9. [Medline].

  76. Moebius FF, Fitzky BU, Lee JN. Molecular cloning and expression of the human delta7-sterol reductase. Proc Natl Acad Sci U S A. 1998 Feb 17. 95(4):1899-902. [Medline].

  77. Nowaczyk MJ, Nakamura LM, Eng B, et al. Frequency and ethnic distribution of the common DHCR7 mutation in Smith-Lemli-Opitz syndrome. Am J Med Genet. 2001 Sep 1. 102(4):383-6. [Medline].

  78. Nowaczyk MJ, Siu VM, Krakowiak PA, Porter FD. Adrenal insufficiency and hypertension in a newborn infant with Smith-Lemli-Opitz syndrome. Am J Med Genet. 2001 Oct 15. 103(3):223-5. [Medline].

  79. Nwokoro NA, Mulvihill JJ. Cholesterol and bile acid replacement therapy in children and adults with Smith-Lemli-Opitz (SLO/RSH) syndrome. Am J Med Genet. 1997 Jan 31. 68(3):315-21. [Medline].

  80. Opitz JM. The RSH syndrome: Paradigmatic metabolic malformation syndrome. New M, ed. Diagnosis and Treatment of the Unborn Child. 1999. 43-55.

  81. Palomaki GE, Bradley LA, Knight GJ, Craig WY, Haddow JE. Assigning risk for Smith-Lemli-Opitz syndrome as part of 2nd trimester screening for Down's syndrome. J Med Screen. 2002. 9(1):43-4. [Medline].

  82. Porter FD. RSH/Smith-Lemli-Opitz syndrome: A multiple congenital Anomaly/Mental retardation syndrome due to an inborn error of cholesterol biosynthesis [In Process Citation]. Mol Genet Metab. 2000 Sep-Oct. 71(1-2):163-74. [Medline].

  83. Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signaling proteins in animal development [published erratum appears in Science 1996 Dec 6;274(5293):1597]. Science. 1996 Oct 11. 274(5285):255-9. [Medline].

  84. Quezado ZM, Veihmeyer J, Schwartz L, et al. Anesthesia and airway management of pediatric patients with Smith-Lemli-Opitz syndrome. Anesthesiology. 2002 Oct. 97(4):1015-9. [Medline].

  85. Roessler E, Belloni E, Gaudenz K. Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly. Hum Mol Genet. 1997 Oct. 6(11):1847-53. [Medline].

  86. Rossiter JP, Hofman KJ, Kelley RI. Smith-Lemli-Opitz syndrome: prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid. Am J Med Genet. 1995 Apr 10. 56(3):272-5. [Medline].

  87. Shackleton CH, Marcos J, Palomaki GE, et al. Dehydrosteroid measurements in maternal urine or serum for the prenatal diagnosis of Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet A. 2007 Sep 15. 143A(18):2129-36. [Medline].

  88. Sharp P, Haan E, Fletcher JM. First-trimester diagnosis of Smith-Lemli-Opitz syndrome. Prenat Diagn. 1997 Apr. 17(4):355-61. [Medline].

  89. Sikora DM, Ruggiero M, Petit-Kekel K. Cholesterol supplementation does not improve developmental progress in Smith-Lemli-Opitz syndrome. J Pediatr. 2004 Jun. 144(6):783-91. [Medline].

  90. Starck L, Lovgren-Sandblom A, Bjorkhem I. Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome. J Intern Med. 2002 Oct. 252(4):314-21. [Medline].

  91. Starck L, Lovgren-Sandblom A, Bjorkhem I. Simvastatin treatment in the SLO syndrome: a safe approach?. Am J Med Genet. 2002 Nov 22. 113(2):183-9. [Medline].

  92. Steiner RD, Linck LM, Flavell DP. Sterol balance in the Smith-Lemli-Opitz syndrome. Reduction In whole body cholesterol synthesis and normal bile acid production [In Process Citation]. J Lipid Res. 2000 Sep. 41(9):1437-47. [Medline].

  93. Tierney E, Nwokoro NA, Porter FD, et al. Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome. Am J Med Genet. 2001 Jan 15. 98(2):191-200. [Medline].

  94. Tint GS. Cholesterol defect in Smith-Lemli-Opitz syndrome [letter]. Am J Med Genet. 1993 Sep 15. 47(4):573-4. [Medline].

  95. Tint GS, Abuelo D, Till M. Fetal Smith-Lemli-Opitz syndrome can be detected accurately and reliably by measuring amniotic fluid dehydrocholesterols. Prenat Diagn. 1998 Jul. 18(7):651-8. [Medline].

  96. Tint GS, Irons M, Elias ER. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994 Jan 13. 330(2):107-13. [Medline].

  97. Tsukahara M, Fujisawa K, Yamamoto K. Smith-Lemli-Opitz syndrome in Japan. Am J Med Genet. 1998 Jan 6. 75(1):118-9. [Medline].

  98. Wanders RJ, Romeijn GJ, Wijburg F. Smith-Lemli-Opitz syndrome: deficient delta 7-reductase activity in cultured skin fibroblasts and chorionic villus fibroblasts and its application to pre- and postnatal detection. J Inherit Metab Dis. 1997 Jul. 20(3):432-6. [Medline].

  99. Wassif CA, Krakowiak PA, Wright BS. Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. Mol Genet Metab. 2005 Jun. 85(2):96-107. [Medline].

  100. Wassif CA, Maslen C, Kachilele-Linjewile S, et al. Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome. Am J Hum Genet. 1998 Jul. 63(1):55-62. [Medline].

  101. Wassif CA, Zhu P, Kratz L, et al. Biochemical, phenotypic and neurophysiological characterization of a genetic mouse model of RSH/Smith--Lemli--Opitz syndrome. Hum Mol Genet. 2001 Mar 15. 10(6):555-64. [Medline].

  102. Waterham HR, Wijburg FA, Hennekam RC. Smith-Lemli-Opitz syndrome is caused by mutations in the 7- dehydrocholesterol reductase gene. Am J Hum Genet. 1998 Aug. 63(2):329-38. [Medline].

  103. Witsch-Baumgartner M, Ciara E, Loffler J, et al. Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitzsyndrome in Europe: evidence for different origins of common mutations. Eur J Hum Genet. 2001 Jan. 9(1):45-50. [Medline].

  104. Zimmerman PA, Hercules DM, Naylor EW. Direct analysis of filter paper blood specimens for identification of Smith-Lemli-Opitz syndrome using time-of-flight secondary ion mass spectrometry. Am J Med Genet. 1997 Jan 31. 68(3):300-4. [Medline].

Child with Smith-Lemli-Opitz syndrome.
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