How is Smith-Lemli-Opitz syndrome (SLOS) diagnosed postnatally?

Updated: Jan 27, 2021
  • Author: Robert D Steiner, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Smith-Lemli-Opitz syndrome is usually suspected clinically, but biochemical studies (and/or genetic studies) are necessary for diagnosis. Plasma total cholesterol and/or low-density lipoprotein (LDL) cholesterol levels may be low but are not universally low. Measurement of plasma sterols, including, at a minimum, cholesterol and 7DHC, is the diagnostic test for Smith-Lemli-Opitz syndrome.

The striking elevation of plasma 7DHC on sterol analysis by gas-liquid chromatography, gas chromatography/mass spectrometry, or tandem mass spectrometry is pathognomonic. The characteristic pattern of low plasma cholesterol levels and the extremely high 7DHC levels define Smith-Lemli-Opitz syndrome. 7DHC is present in plasma in healthy individuals in trace quantities. Cholesterol levels are not always below the reference range; screening by plasma cholesterol measurement alone should be discouraged.

Sterol analysis has proven useful for diagnosing patients with the classical phenotype, prenatal cases identified through maternal serum screening, and patients with more subtle physical findings and intellectual disability. In the United States, a handful of laboratories perform this analysis, and a timely query to the Genetic Testing Registry is extremely useful in identifying laboratories performing this analysis.

Mutational analyses/molecular genetic testing are useful confirmatory tests and important for prenatal diagnosis in a family with a known mutation and, when appropriate, for carrier testing.

Reserve enzyme analysis for atypical cases or cases yielding equivocal results by other methods.

Electrolytes and, possibly, cortisol and adrenocorticotropic hormone (ACTH) may be useful in ruling out adrenal insufficiency.

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