Relation between biomarkers and clinical severity in patients with Smith–Lemli–Opitz syndrome

  title={Relation between biomarkers and clinical severity in patients with Smith–Lemli–Opitz syndrome},
  author={Anna V. Ol{\'a}h and Gabriella P. Szab{\'o} and J{\'o}zsef Varga and L{\'i}dia Balogh and Gy{\"o}rgyi Cs{\'a}b{\'i} and Violetta Cs{\'a}kv{\'a}ry and Wolfgang Erwa and Istv{\'a}n Balogh},
  journal={European Journal of Pediatrics},
Smith–Lemli–Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n = 4, clinical score <20) was 0.5–18 years, cholesterol was 2.37 ± 0.8 mmol/L, and 7DHC was 0.38 ± 0.14 mmol/L. In the group… 
Smith-Lemli-Opitz syndrome: clinical and biochemical correlates
It is suggested that screening for adrenal insufficiency and for hypoparathyroidism, hypothyroidism and immunodeficiency, should be done routinely in infants diagnosed early with SLOS, in the context of the emerging evidence of the importance of cholesterol in morphogenesis and steroidogenesis.
A Case of Smith-Lemli-Opitz Syndrome Diagnosed with Hypertrophic Pyloric Stenosis
Infants with progressive projectile vomiting, feeding problems, and multiple anomalies with dysmorphic facial anomalies may be suspected to have SLOS and their families should be advised to have genetic testing and genetic counseling.
[Inborn error of cholesterol biosynthesis: Smith-Lemli-Opitz syndrome].
The authors summarize the pathophysiology, epidemiology, clinical picture, diagnostics and therapy of the disease based on a review of the international literature.
Dietary cholesterol supplementation and inhibitory factor 1 serum levels in two dizygotic Smith-Lemli-Opitz syndrome twins: a case report
The findings confirm that IF 1 could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF 1 as a new modulator of cholesterol levels.
Novel DHCR7 mutation in a case of Smith–Lemli–Opitz syndrome showing 46,XY disorder of sex development
A Japanese case with 46,XY disorder of sex development and Y-shaped 2–3 toe syndactyly with DHCR7 gene analysis revealed compound heterozygous mutations including the novel mutation H442R which led to starting cholesterol treatment at an early age.
Vulnerability of DHCR7+/− mutation carriers to aripiprazole and trazodone exposure[S]
The results suggest that DHCR7 carriers have increased vulnerability to both ARI and TRZ exposure compared with CTRs, and the 1–3% of the population may be more likely to sustain deleterious health consequences on exposure to compounds that increase levels of 7-DHC, especially during brain development.
Determination of the allelic frequency in Smith–Lemli–Opitz syndrome by analysis of massively parallel sequencing data sets
The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence.
Human Cholesterol Biosynthesis Defects
Clinical, biochemical and molecular aspects of the known human cholesterol biosynthesis defects are reviewed, reflecting the important role of cholesterol, and its intermediary metabolites, in embryogenesis and development.
Medication effects on developmental sterol biosynthesis
Studies of human dermal fibroblasts from individuals who carry DCHR7 +/- single allele mutations suggest that the same gene*medication interaction also occurs in humans, and public health relevance is high, as DHCR7-inhibitors can be considered teratogens, and are commonly used by pregnant women.


Mutational Spectrum of Smith-Lemli-Opitz Syndrome Patients in Hungary
Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases and these mutations show a large interethnic variability.
Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism.
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.
Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.
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.
Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management
  • F. Porter
  • Medicine
    European Journal of Human Genetics
  • 2008
This review discusses the clinical aspects and diagnosis of SLOS, therapeutic interventions and the current understanding of pathophysiological processes involved in SLOS.
Effects of cholesterol and simvastatin treatment in patients with Smith–Lemli–Opitz syndrome (SLOS)
Cholesterol as well as additional simvastatin decreased the plasma (7+8–DHC)/cholesterol ratio, however, the mechanism leading to the decreasing ratio was different and was due to an increasing cholesterol concentration in the cholesterol-only cohort, while a decreasing 7- and 8-dehydrocholesterol concentration was demonstrated in the cohort receiving additional simVastatin.
Cholesterol and bile acid replacement therapy in children and adults with Smith-Lemli-Opitz (SLO/RSH) syndrome.
The experience with bile acid and/or cholesterol replacement therapy in six patients with SLOS, now aged 3-27 years, with a confirmed biochemical diagnosis, is reported.
A patient with Smith–Lemli–Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement
This patient demonstrates that the c.964-1G>C/p.G366V genotype of combined heterozygosity is associated with a typical form of SLO syndrome along with moderately altered laboratory findings and a favorable biochemical response to cholesterol and simvastatin treatment.
First Trimester Prenatal Diagnosis of Smith-Lemli-Opitz Syndrome(7-Dehydrocholesterol Reductase Deficiency)
It is concluded that synthesis of cholesterol via 7-DHC is occurring in the placenta and/or fetus at 10 wk of gestation and that prenatal diagnosis by CV biopsy is possible.
Incidence of Smith-Lemli-Opitz syndrome in Ontario, Canada.
The observation that five unrelated cases of SLOS were diagnosed in Ontario during a 12-month period has implications for prenatal and newborn screening for this potentially treatable inherited disorder.