Smith-Lemli-Opitz Syndrome Clinical Presentation

  • Author: Robert D Steiner, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jul 12, 2011
 

History

The following signs and symptoms may be noted:

  • Lethargy
  • Obtundation or coma
  • Respiratory failure
  • Hearing loss
  • Visual loss
  • Vomiting
  • Feeding difficulties
  • Failure to thrive
  • Constipation
  • Cyanosis
  • Congestive heart failure
  • Photosensitivity

Neuropsychiatric and neurodevelopmental abnormalities are common and include variable mental retardation, aberrant behavior, and autism.

  • The aberrant behavior of the older child can include antisocial, self-destructive, and violent acts or withdrawal, self-stimulation, and frank autism. Indeed, autism is quite common in Smith-Lemli-Opitz syndrome (SLOS).[16]
  • The risk for neuropsychiatric disorders also appears to be increased in adults with Smith-Lemli-Opitz syndrome.
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Physical

Intrauterine growth retardation (IUGR) is common, as is short stature or abnormally low weight for height, altered muscle tone (hypotonia), and often a distinctive shrill cry.

Rarely, hydrops fetalis occurs.

Congenital anomalies evident upon physical examination may include the following:

  • Microcephaly
  • Intracranial germinoma[17]
  • Broad nasal tip with anteverted nostrils
  • Micrognathia
  • Ptosis of eyelids
  • Epicanthal folds
  • Strabismus
  • Cataracts (may also develop postnatally[18] )
  • Broad maxillary alveolar ridges
  • Slanted or low-set ears
  • Syndactyly of second and third toes
  • Postaxial polydactyly
  • Hypospadias or cryptorchidism in males and, occasionally, complete sex reversal (ie, 46,XY females)
  • Cleft palate
  • Heart murmur or cyanosis or respiratory distress secondary to congenital cardiac defects
  • Respiratory distress secondary to pulmonary anomalies

Considerable phenotypic variance may be present within affected families, between individuals, and over time in the neonate, infant, child, and adult with Smith-Lemli-Opitz syndrome. Mildly affected individuals may exhibit only subtle dysmorphic facies and learning disabilities, whereas severely affected individuals may have complete sex reversal, lethal cardiac and brain malformations, microcephaly, cleft palate, and multiorgan system failure.

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Causes

Analysis of family pedigrees has revealed that Smith-Lemli-Opitz syndrome is transmitted in an autosomal recessive fashion as an multiple congenital anomaly (MCA)/MR syndrome. Three different groups reported the molecular genetic basis for Smith-Lemli-Opitz syndrome simultaneously.

Smith-Lemli-Opitz syndrome is caused by mutations in the DHCR7 gene, the gene that codes for the enzyme DHCR7 that normally converts 7DHC to cholesterol in the final step of the cholesterol synthetic pathway. Mapping of the DHCR7 gene established the chromosomal position on band 11q12.13. Subsequent mutational analyses by several groups have identified a wide variety of different mutations within the DHCR7 gene with several common mutations.

Most patients with Smith-Lemli-Opitz syndrome have proven to be compound heterozygotes. This genetic heterogeneity points to possible phenotype-genotype corollaries.

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Contributor Information and Disclosures
Author

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research; Faculty, Pediatrics, Molecular and Medical Genetics, and Program in Molecular and Cellular Biosciences; Vice Chair for Research in Pediatrics, Doernbecher Children's Hospital, Oregon Health and Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital

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, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Specialty Editor Board

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 American Society of Human Genetics

Disclosure: Nothing to disclose.

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.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Acknowledgments

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

References

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

  2. Opitz JM. RSH (so-called Smith-Lemli-Opitz) syndrome. Curr Opin Pediatr. Aug 1999;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. May 1 1994;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. Dec 2006;47(12):2789-98. [Medline].

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

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

  7. 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. Feb 14 2000;90(4):347-50. [Medline].

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

  9. 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. Jul 1 2003;120A(1):139-41. [Medline].

  10. 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. Apr 2008;45(4):200-9. [Medline].

  11. 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].

  12. 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. Jan 15 2005;132(2):144-51. [Medline].

  13. 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. Dec 28 1998;80(5):501-5. [Medline].

  14. 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. Oct 2010;121(2):85-91. [Medline]. [Full Text].

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

  16. 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. Jul 15 2006;140(14):1511-8. [Medline].

  17. 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. Sep 2008;30(9):689-91. [Medline].

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

  19. 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. Mar 1999;84(3):1157-9. [Medline].

  20. 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. Jan 31 1997;68(3):294-9. [Medline].

  21. 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. Jan 2010;152A(1):91-5. [Medline]. [Full Text].

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

  23. 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. Jun 2007;30(3):375-87. [Medline].

  24. 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. Jun 2007;30(3):375-87. [Medline].

  25. 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. Oct 15 2001;103(3):223-5. [Medline].

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

  27. 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. Apr 10 1995;56(3):281-5. [Medline].

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

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

  30. 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].

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

  32. 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].

  33. 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. Feb 12 1999;82(4):355-8. [Medline].

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

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

  36. 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. Jan 31 1997;68(3):322-7. [Medline].

  37. 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. Jan 31 1997;68(3):263-9. [Medline].

  38. 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. Sep 1995;15(9):855-8. [Medline].

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

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

  41. 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. Jan 31 1997;68(3):305-10. [Medline].

  42. 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. Jul 7 1998;95(14):8181-6. [Medline].

  43. 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. Sep-Oct 2004;83(1-2):175-83. [Medline].

  44. 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.

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

  46. 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. Jan 31 1997;68(3):288-93. [Medline].

  47. 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. Jan 31 1997;68(3):282-7. [Medline].

  48. 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. Oct 1998;21(7):761-8. [Medline].

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

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

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

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

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

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

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

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

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

  58. 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. Sep 18 2000;94(3):214-27. [Medline].

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

  60. 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. Mar 2000;20(3):238-40. [Medline].

  61. 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. Aug 28 2000;93(5):360-5. [Medline].

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

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

  64. McKusick VA. OMIM Number:270400. Online Mendelian Inheritance in Man, OMIM. Available at http://www.ncbi.nlm.nih.gov/omim/. Accessed October 3, 1999.

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

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

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

  68. 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. Sep 1 2001;102(4):383-6. [Medline].

  69. 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. Oct 15 2001;103(3):223-5. [Medline].

  70. 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. Jan 31 1997;68(3):315-21. [Medline].

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

  72. 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].

  73. 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. Sep-Oct 2000;71(1-2):163-74. [Medline].

  74. 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. Oct 11 1996;274(5285):255-9. [Medline].

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

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

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

  78. 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. Sep 15 2007;143A(18):2129-36. [Medline].

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

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

  81. 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. Oct 2002;252(4):314-21. [Medline].

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

  83. 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. Sep 2000;41(9):1437-47. [Medline].

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

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

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

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

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

  89. 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. Jul 1997;20(3):432-6. [Medline].

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

  91. 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. Jul 1998;63(1):55-62. [Medline].

  92. 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. Mar 15 2001;10(6):555-64. [Medline].

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

  94. 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. Jan 2001;9(1):45-50. [Medline].

  95. 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. Jan 31 1997;68(3):300-4. [Medline].

 
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