The Smith–Lemli–Opitz syndrome: a novel metabolic way of understanding developmental biology, embryogenesis, and dysmorphology

@article{Nowaczyk2001TheSS,
  title={The Smith–Lemli–Opitz syndrome: a novel metabolic way of understanding developmental biology, embryogenesis, and dysmorphology},
  author={Malgorzata J.M. Nowaczyk and John S. Waye},
  journal={Clinical Genetics},
  year={2001},
  volume={59}
}
The brief history of the Smith–Lemli–Opitz syndrome (SLOS) (MIM 270400) reflects that of latter 20th century dysmorphology and biochemical and molecular genetics: from its first description as a rare but characteristic multiple malformation syndrome known only to a handful of dysmorphologists, to a relatively common Garrodian defect with a complex molecular basis that has captured the attention of researchers and basic scientists from the fields as diverse as embryology, developmental biology… 
Smith–Lemli–Opitz syndrome: Phenotype, natural history, and epidemiology
  • M. Nowaczyk, M. Irons
  • Biology, Medicine
    American journal of medical genetics. Part C, Seminars in medical genetics
  • 2012
TLDR
The physical and behavioral phenotype of SLOS, the diagnostic approaches, the natural history from the prenatal period to adulthood, and current understanding of the pathophysiology ofSLOS are discussed.
Smith-Lemli-Opitz syndrome: new mutation with a mild phenotype.
TLDR
A female infant with an exceptionally mild phenotype of SLOS is reported on, in whom molecular studies identified a new mutation in DHCR7, presumably associated with significant residual enzyme activity and milder expression of clinical phenotype.
Molecular screening of Smith–Lemli–Opitz syndrome in pregnant women from the Czech Republic
TLDR
The most frequently found mutations, c.964-1> C and p.W151X, are also the most severe ones, which suggests that the biochemical screening of pregnant women probably uncovers mainly more severely affected fetuses.
Smith-Lemli-Opitz syndrome: carrier frequency and spectrum of DHCR7 mutations in Canada
TLDR
The spectrum of severity extends from prenatal death with holoprosencephaly or other lethal malformations to minimally physically affected patients with normal intelligence or minimal intellectual impairment, showing both founder effects and recurrent mutations.
Smith-Lemli-Opitz syndrome : carrier frequency and spectrum of DHCR 7 mutations in Canada
Smith-Lemli-Opitz syndrome (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis resulting from deficient 3β-hydroxysterol ∆-reductase (DHCR7) activity. 2 Patients with
Clinical utility gene card for: Smith-Lemli-Opitz Syndrome [SLOS]
TLDR
A correlation of the genotype with the SLOS phenotype7 demonstrates that patients carrying homozygous or compound heterozygous functional null DHCR7 alleles have the most severe phenotypes.
A Novel Mutation of the DHCR7 Gene in a Sicilian Compound Heterozygote with Smith-Lemli-Opitz Syndrome
TLDR
A Sicilian patient is described, a carrier of a novel mutation of the DHCR7 gene (1251N), which is responsible in a compound heterozygous state for a severe form of Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz Syndrome
TLDR
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple-anomaly / cognitive impairment syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase.
The implications of 7-dehydrosterol-7-reductase deficiency (Smith–Lemli–Opitz syndrome) to neurosteroid production
TLDR
Analysis by GC/MS of urinary steroids excreted by post-pubertal females confirmed the presence of neurosteroid-like compounds in SLOS patient's urine, and it is likely that mechanisms for their synthesis are operable in this organ.
Smith‐Lemli‐Opitz Mutations in Unexplained Stillbirths
TLDR
The authors detected SLOS mutations in only 0.7% of stillbirths, which does not support a strong association between unrecognized DHCR7 mutations and stillbirth.
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References

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Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism.
TLDR
A comparison of the frequency of anomalies in biochemically identified patients with similar data from previously reported clinical series suggests that up to 25% of reports of RSH/SLO in the literature may describe genetic conditions other than RSH-SLO with 7-DHC-emia.
Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene.
TLDR
Data demonstrate that Smith-Lemli-Opitz syndrome is caused by mutations in the gene coding for 7-dehydrocholesterol reductase, which catalyzes the final step in the cholesterol-biosynthesis pathway.
Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz syndrome.
TLDR
A rat model is developed that presents with abnormalities observed as early as gestational day 12 that appear to be consistent with some of those subsequent malformations that comprise the human syndrome, and the potential basis for the selective vulnerability of this cell population and the impact of its vulnerability relative to subsequent dysmorphogenesis is discussed.
Smith-Lemli-Opitz syndrome: evidence of T93M as a common mutation of Δ7-sterol reductase in Italy and report of three novel mutations
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis characterised by facial dysmorphisms, mental retardation and multiple congenital anomalies. SLOS
RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis.
  • F. Porter
  • Biology, Medicine
    Molecular genetics and metabolism
  • 2000
TLDR
Identification of the biochemical basis of RSH/SLOS has led to development of therapeutic regimens based on dietary cholesterol supplementation and has increased the understanding of the role cholesterol plays during embryonic development.
Variant RSH/Smith-Lemli-Opitz syndrome with atypical sterol metabolism.
TLDR
The findings suggest that these mildly affected RSH/SLOS sibs may have a genetic disorder of sterol metabolism that is related to but biochemically different from classical RSH /SLOS, possibly one affecting intracellular transport of sterols.
Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.
TLDR
It is concluded that accurate prenatal diagnosis of RSH/ SLOS is possible by sterol analysis of AF and, most likely, CV specimens as well and that MSuE3 levels in combination with sonography may provide useful diagnostic and prognostic information in the absence of a family history of R SH/SLOS.
Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol metabolism affect the function of Sonic Hedgehog?
TLDR
Clinical, biochemical, and molecular studies suggest that HPE and other malformations in SLOS may be caused by incomplete or abnormal modification of the sonic hedgehog protein and, possible, other patterning proteins of the hedgehog class, a hypothesis testable in somatic cell systems.
Novel 7-DHCR mutation in a child with Smith-Lemli-Opitz syndrome.
TLDR
This work reports the first molecular characterization of an Italian SLOS patient and finds that his paternal 7DHCR allele, of Arab origin, harbored a novel P329L mutation which in combination with a maternal splice-site (IVS8-1 G>C) mutation resulted in a relatively milder phenotype.
The Smith-Lemli-Opitz syndrome.
TLDR
The recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its effects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome.
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