Diagnosing SLOS: Lab Tests and Genetics
At a Glance
Smith-Lemli-Opitz syndrome (SLOS) is definitively diagnosed using a specialized blood test called sterol profiling, which measures elevated 7-DHC levels. A standard cholesterol test is not sufficient. The diagnosis is then confirmed by identifying mutations in the DHCR7 gene.
Confirming a diagnosis of Smith-Lemli-Opitz Syndrome (SLOS) requires more than a standard blood test. Because SLOS is a metabolic disorder that affects how the body creates its own cholesterol, doctors must look for specific chemical “fingerprints” in the blood and confirm the finding through genetic analysis [1][2].
The “Gold Standard” Lab Tests
If you suspect SLOS, a standard total cholesterol panel is not enough. This is because common laboratory machines often cannot distinguish between actual cholesterol and the precursor molecules that build up in SLOS [3].
Sterol Profiling
The definitive way to diagnose SLOS biochemically is through sterol profiling using advanced technology called Gas Chromatography-Mass Spectrometry (GC-MS) or LC-MS/MS [2][4]. These tests are designed to measure:
- 7-Dehydrocholesterol (7-DHC): This is the primary marker for SLOS. In affected individuals, levels of 7-DHC are significantly elevated [1][4].
- 8-Dehydrocholesterol (8-DHC): This is another precursor that builds up alongside 7-DHC and helps confirm the diagnosis [3][2].
- Low Cholesterol: While not always present in every case, many individuals will also show abnormally low total cholesterol levels [1].
Genetic Confirmation
While the blood test shows “what” is happening, genetic testing shows “why.” SLOS is caused by mutations in the DHCR7 gene [1][5].
- Autosomal Recessive Inheritance: To have SLOS, a person must inherit two faulty copies of the DHCR7 gene—one from each parent [1].
- Confirming the Diagnosis: Genetic testing looks for these specific pathogenic variants (mutations). Finding two such mutations confirms the biochemical diagnosis and can help families understand the 25% risk of the condition recurring in future pregnancies [5][6].
Potential “False Positives” and Confounders
It is important to tell your doctor about all current medications, as some drugs can mimic the chemical signs of SLOS. This is sometimes called “pseudometabolic” elevation of 7-DHC [7].
- Medications: Certain prescription drugs, including the antipsychotic aripiprazole (Abilify), the antidepressant trazodone, and some antifungal treatments, can interfere with the same enzyme that is affected in SLOS, causing 7-DHC levels to rise even if the person does not have the genetic condition [7][8][9].
Prenatal Diagnosis
For families who know they carry the DHCR7 mutation, or when an ultrasound shows physical features like a cleft palate or webbed toes, prenatal testing is available [10].
- Amniocentesis: A sample of amniotic fluid can be tested for elevated 7-DHC levels or for the specific family mutations in the DHCR7 gene [10][5].
- CVS (Chorionic Villus Sampling): This procedure tests a small piece of the placenta early in pregnancy to look for the known genetic mutations [6].
Understanding these diagnostic tools empowers you to ensure you or your child receives the most accurate testing possible, avoiding the pitfalls of standard cholesterol screens.
Common questions in this guide
Why isn't a standard cholesterol test enough to diagnose SLOS?
What is the primary lab marker for SLOS?
How is a Smith-Lemli-Opitz syndrome diagnosis confirmed?
Can medications cause a false positive SLOS test?
Can SLOS be diagnosed before a baby is born?
Questions to Ask Your Doctor
Curated prompts to bring to your next appointment.
- 1.Was the testing performed using Gas Chromatography-Mass Spectrometry (GC-MS) or LC-MS/MS?
- 2.What were the exact levels of 7-DHC and 8-DHC found in the blood?
- 3.Could any current medications, like aripiprazole or certain antifungals, be causing a 'false positive' or 'pseudometabolic' elevation in 7-DHC?
- 4.How do the specific DHCR7 gene mutations identified in the genetic test correlate with the symptoms we are seeing?
- 5.If planning a pregnancy, what are the options for prenatal diagnosis or testing?
Questions For You
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References
References (10)
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PMID: 33528983 - 8
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ACS pharmacology & translational science 2021; (4(2)):848-857 doi:10.1021/acsptsci.1c00012.
PMID: 33860207 - 9
Inhibitors of 7-Dehydrocholesterol Reductase: Screening of a Collection of Pharmacologically Active Compounds in Neuro2a Cells.
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Chemical research in toxicology 2016; (29(5)):892-900 doi:10.1021/acs.chemrestox.6b00054.
PMID: 27097157 - 10
Prenatal diagnosis of holoprosencephaly associated with Smith-Lemli-Opitz syndrome (SLOS) in a 46,XX fetus.
Travessa A, Dias P, Rocha P, Sousa AB
Taiwanese journal of obstetrics & gynecology 2017; (56(4)):541-544 doi:10.1016/j.tjog.2017.01.012.
PMID: 28805615
This page explains diagnostic testing for SLOS for educational purposes only. Always consult a clinical geneticist or your child's pediatrician for interpreting specific lab results and genetic testing.
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