Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations of the DHCR7 gene. It is characterized by multiple congenital anomalies and mental retardation.

Systematic

Congenital abnormalities of the kidney and urinary tract
Acro-renal-ocular syndrome
Aplasia of lacrimal and salivary glands
Autosomal dominant Robinow syndrome 1
Autosomal recessive Robinow syndrome
BMP7
BNAR syndrome
Brain malformations with urinary tract defects
Branchio-oculo-facial syndrome
Branchiootic syndrome
Branchiootorenal dysplasia
CHARGE syndrome
CHD1L
Congenital anomalies of kidney and urinary tract 1
Congenital anomalies of kidney and urinary tract 2
Congenital hypogonadotropic hypogonadism with anosmia 1
Congenital hypogonadotropic hypogonadism without anosmia 5
Denys-Drash syndrome
Fraser syndrome
Frasier syndrome
Goldberg-Shprintzen syndrome
IVIC syndrome
Ivemark syndrome
Kabuki syndrome
Lacrimoauriculodentodigital syndrome
Mowat-Wilson syndrome
Papillorenal syndrome
Renal cysts and diabetes (RCAD)
Renal dysplasia with hypopituitarism and diabetes
Renal hypodysplasia/aplasia
Renal tubular dysgenesis
SERKAL syndrome
Simpson-Golabi-Behmel syndrome
Smith-Lemli-Opitz syndrome
DHCR7
Somatic nephroblastoma
Susceptibility to cystic renal dysplasia
Syndromic microphthalmia 6
Urofacial syndrome
Vesicoureteral reflux
WAGR syndrome

References:

1.

Porter JA et al. (1996) Cholesterol modification of hedgehog signaling proteins in animal development.

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2.

Shefer S et al. (1995) Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes.

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3.

Wassif CA et al. (1998) Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome.

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4.

Fitzky BU et al. (1998) Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome.

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5.

Nowaczyk MJ et al. (1998) Smith-Lemli-Opitz syndrome: phenotypic extreme with minimal clinical findings.

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6.

Yu H et al. (2000) 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.

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7.

Yu H et al. (2000) Spectrum of Delta(7)-dehydrocholesterol reductase mutations in patients with the Smith-Lemli-Opitz (RSH) syndrome.

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8.

Witsch-Baumgartner M et al. (2001) Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations.

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9.

Wassif CA et al. (2001) Biochemical, phenotypic and neurophysiological characterization of a genetic mouse model of RSH/SmithLemliOpitz syndrome.

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10.

Nowaczyk MJ et al. (2001) DHCR7 genotypes of cousins with Smith-Lemli-Opitz syndrome.

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11.

Nowaczyk MJ et al. (2001) Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype.

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12.

Langius FA et al. (2003) Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome.

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13.

Kovarova M et al. (2006) Cholesterol deficiency in a mouse model of Smith-Lemli-Opitz syndrome reveals increased mast cell responsiveness.

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14.

Witsch-Baumgartner M et al. (2008) Age and origin of major Smith-Lemli-Opitz syndrome (SLOS) mutations in European populations.

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15.

Koo G et al. (2010) Discordant phenotype and sterol biochemistry in Smith-Lemli-Opitz syndrome.

[^]
16.

Kalb S et al. (2012) High frequency of p.Thr93Met in Smith-Lemli-Opitz syndrome patients in Turkey.

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17.

Witsch-Baumgartner M et al. (2004) Maternal apo E genotype is a modifier of the Smith-Lemli-Opitz syndrome.

[^]
18.

Lazarin GA et al. (2013) An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.

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19.

Roux C et al. (1979) Teratogenic action and embryo lethality of AY 9944R. Prevention by a hypercholesterolemia-provoking diet.

[^]
20.

None (1975) Smith-Lemli-Opitz syndrome: review and report of two affected siblings.

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21.

Fierro M et al. (1977) Smith-Lemli-Opitz syndrome: neuropathological and ophthalmological observations.

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22.

Cherstvoy ED et al. () The pathological anatomy of the Smith-Lemli-Opitz syndrome.

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23.

Fukazawa R et al. () Normal Y sequences in Smith-Lemli-Opitz syndrome with total failure of masculinization.

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24.

Lachman MF et al. (1991) Brief clinical report: a 46,XY phenotypic female with Smith-Lemli-Opitz syndrome.

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25.

McKeever PA et al. (1990) Smith-Lemli-Opitz syndrome. II: A disorder of the fetal adrenals?

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26.

Berry R et al. (1989) Apparent Smith-Lemli-Opitz syndrome and Miller-Dieker syndrome in a family with segregating translocation t(7;17)(q34;p13.1).

[^]
27.

Chasalow FI et al. () Possible abnormalities of steroid secretion in children with Smith-Lemli-Opitz syndrome and their parents.

[^]
28.

Bialer MG et al. (1987) Female external genitalia and müllerian duct derivatives in a 46,XY infant with the smith-lemli-Opitz syndrome.

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29.

Opitz JM et al. (1987) Smith-Lemli-Opitz (RSH) syndrome bibliography.

[^]
30.

Joseph DB et al. (1987) Genitourinary abnormalities associated with the Smith-Lemli-Opitz syndrome.

[^]
31.

Scarbrough PR et al. (1986) An additional case of Smith-Lemli-Opitz syndrome in a 46,XY infant with female external genitalia.

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32.

Curry CJ et al. (1987) Smith-Lemli-Opitz syndrome-type II: multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality.

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33.

Belmont JW et al. (1987) Two cases of severe lethal Smith-Lemli-Opitz syndrome.

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34.

Donnai D et al. (1986) The lethal multiple congenital anomaly syndrome of polydactyly, sex reversal, renal hypoplasia, and unilobular lungs.

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35.

Fried K et al. (1972) Smith-Lemli-Opitz syndrome in an adult.

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36.

Cotlier E et al. (1971) Cataracts in the Smith-Lemli-Opitz syndrome.

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37.

Suzuki K et al. (1971) Cellular degeneration in developing central nervous system of rats produced by hypocholesteremic drug AY9944.

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38.

None (1969) Syndrome of retardation with urogenital and skeletal anomalies (Smith-Lemli-Opitz syndrome): clinical features and mode of inheritance.

[^]
39.

Deaton JG et al. (1973) Smith-Lemli-Optiz syndrome in a 23-year-old man.

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40.

Nevo S et al. (1972) Smith-Lemli-Opitz syndrome in an inbred family.

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41.

Hoefnagel D et al. (1969) The Smith-Lemli-Opitz syndrome in an adult male.

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42.

Lowry RB et al. (1968) Micrognathia, polydactyly, and cleft palate.

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43.

Blair HR et al. (1966) A syndrome characterized by mental retardation, short stature, craniofacial dysplasia, and genital anomalies occurring in siblings.

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44.

Dallaire L et al. (1966) The syndrome of retardation with urogenital and skeletal anomalies in siblings.

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45.

Kenis H et al. (1967) A familial syndrome of mental retardation in association with multiple congenital anomalies resembling the syndrome of Smith-Lemli-Opitz.

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46.

Rutledge JC et al. (1984) A "new" lethal multiple congenital anomaly syndrome: joint contractures, cerebellar hypoplasia, renal hypoplasia, urogenital anomalies, tongue cysts, shortness of limbs, eye abnormalities, defects of the heart, gallbladder agenesis, and ear malformations.

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47.

Greene C et al. (1984) Smith-Lemli-Opitz syndrome in two 46,XY infants with female external genitalia.

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48.

None (1983) Brief clinical report: familial neonatally lethal syndrome of hypoplastic left heart, absent pulmonary lobation, polydactyly, and talipes, probably Smith-Lemli-Opitz (RSH) syndrome.

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49.

None (1983) Editorial comment: variability in the Smith-Lemli-Opitz syndrome: overlap with the Meckel syndrome.

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50.

Patterson K et al. (1983) Hirschsprung disease in a 46,XY phenotypic infant girl with Smith-Lemli-Opitz syndrome.

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51.

Tint GS et al. (1995) Correlation of severity and outcome with plasma sterol levels in variants of the Smith-Lemli-Opitz syndrome.

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52.

Opitz JM et al. (1994) Cholesterol metabolism in the RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD conference.

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53.

Irons M et al. (1993) Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome.

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54.

Alley TL et al. (1995) Identification of a yeast artificial chromosome clone spanning a translocation breakpoint at 7q32.1 in a Smith-Lemli-Opitz syndrome patient.

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55.

Xu G et al. (1995) Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in rats.

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56.

Johnson JA et al. (1994) Prenatal diagnosis of Smith-Lemli-Opitz syndrome, type II.

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57.

McGaughran J et al. (1994) Diagnosis of Smith-Lemli-Opitz syndrome.

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58.

Opitz JM et al. (1994) Smith-Lemli-Opitz (RSH) syndrome bibliography: 1964-1993.

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59.

Irons M et al. (1994) Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient.

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60.

Wallace M et al. (1994) Smith-Lemli-Opitz syndrome in a female with a de novo, balanced translocation involving 7q32: probable disruption of an SLOS gene.

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61.

None (1993) Cholesterol defect in Smith-Lemli-Opitz syndrome.

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62.

Tint GS et al. (1994) Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome.

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63.

Hyett JA et al. (1995) Increased first trimester nuchal translucency as a prenatal manifestation of Smith-Lemli-Opitz syndrome.

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64.

Dallaire L et al. (1995) Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7-dehydrocholesterol in amniotic fluid.

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65.

Salen G et al. (1996) Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.

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66.

De Die-Smulders C et al. (1996) Confirmation of defective cholesterol biosynthesis in 2 previously described adult sibs with Smith-Lemli-Opitz syndrome.

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67.

Cormier-Daire V et al. (1996) Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz and the lethal acrodysgenital syndromes.

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68.

Guzzetta V et al. (1996) Clinical and biochemical screening for Smith-Lemli-Opitz syndrome. Italian SLOS Collaborative Group.

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69.

Seller MJ et al. (1997) Phenotypic diversity in the Smith-Lemli-Opitz syndrome.

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70.

Pauli RM et al. (1997) Smith-Lemli-Opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome.

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71.

Cunniff C et al. (1997) Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism.

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72.

Alley TL et al. (1997) Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with t(7;20) (q32.1;q13.2).

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73.

Honda A et al. (1997) Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts: diagnosis of a biochemically atypical case of the syndrome.

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74.

Honda A et al. (1997) Screening for abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome: rapid determination of plasma 7-dehydrocholesterol by ultraviolet spectrometry.

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75.

Ness GC et al. (1997) Increased expression of low-density lipoprotein receptors in a Smith-Lemli-Opitz infant with elevated bilirubin levels.

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76.

Elias ER et al. (1997) Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS)

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77.

Irons M et al. (1997) Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial.

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78.

Nwokoro NA et al. (1997) Cholesterol and bile acid replacement therapy in children and adults with Smith-Lemli-Opitz (SLO/RSH) syndrome.

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79.

Dehart DB et al. (1997) Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz syndrome.

[^]
80.

Irons MB et al. (1998) Prenatal diagnosis of Smith-Lemli-Opitz syndrome.

[^]
81.

Ryan AK et al. (1998) Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype.

[^]
82.

None (1998) RSH/Smith-Lemli-Opitz syndrome: mutations and metabolic morphogenesis.

[^]
83.

Anderson AJ et al. (1998) Variant RSH/Smith-Lemli-Opitz syndrome with atypical sterol metabolism.

[^]
84.

Atchaneeyasakul LO et al. (1998) Eye findings in 8 children and a spontaneously aborted fetus with RSH/Smith-Lemli-Opitz syndrome.

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85.

Kratz LE et al. (1999) Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.

[^]
86.

Andersson HC et al. (1999) Adrenal insufficiency in Smith-Lemli-Opitz syndrome.

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87.

Shackleton CH et al. (1999) Equine type estrogens produced by a pregnant woman carrying a Smith-Lemli-Opitz syndrome fetus.

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88.

Neklason DW et al. (1999) Biochemical variants of Smith-Lemli-Opitz syndrome.

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89.

Anstey AV et al. (1999) Photosensitivity in the Smith-Lemli-Opitz syndrome: the US experience of a new congenital photosensitivity syndrome.

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90.

Honda M et al. (2000) Regulation of cholesterol biosynthetic pathway in patients with the Smith-Lemli-Opitz syndrome.

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91.

Linck LM et al. (2000) Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome.

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92.

Battaile KP et al. (2001) Carrier frequency of the common mutation IVS8-1G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome.

[^]
93.

Azurdia RM et al. (2001) Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome.

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94.

Tierney E et al. (2001) Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome.

[^]
95.

Nowaczyk MJ et al. (2001) Incidence of Smith-Lemli-Opitz syndrome in Ontario, Canada.

[^]
96.

Nowaczyk MJ et al. (2001) Adrenal insufficiency and hypertension in a newborn infant with Smith-Lemli-Opitz syndrome.

[^]
97.

None (2003) Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.

[^]
98.

WEBER JW et al. (1960) [Typus Rostockiensis Ullrich-Feichtiger. Dyscranio-pygo-phalangia].

[^]
99.

SMITH DW et al. (1964) A NEWLY RECOGNIZED SYNDROME OF MULTIPLE CONGENITAL ANOMALIES.

[^]
100.

PINSKY L et al. (1965) A FAMILIAL SYNDROME OF FACIAL AND SKELETAL ANOMALIES ASSOCIATED WITH GENITAL ABNORMALITY IN THE MALE AND NORAML GENITALS IN THE FEMALE: ANOTHER CAUSE OF MALE PSEUDOHERMAPHRODITISM.

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101.

Goldenberg A et al. (2004) Antenatal manifestations of Smith-Lemli-Opitz (RSH) syndrome: a retrospective survey of 30 cases.

[^]
102.

Jezela-Stanek A et al. (2006) Maternal urinary steroid profiles in prenatal diagnosis of Smith-Lemli-Opitz syndrome: first patient series comparing biochemical and molecular studies.

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103.

Sikora DM et al. (2006) The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome.

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104.

Jiang XS et al. (2010) Activation of Rho GTPases in Smith-Lemli-Opitz syndrome: pathophysiological and clinical implications.

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105.

OMIM.ORG article

Omim 270400 [^]
106.

Orphanet article

Orphanet ID 818 [^]
107.

Wikipedia article

Wikipedia EN (Smith–Lemli–Opitz_syndrome) [^]
Update: April 29, 2019