Smith-Lemli-Opitz syndrome

Prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid

Judith P. Rossiter, K. J. Hofman, R. I. Kelley

Research output: Contribution to journalArticle

Abstract

Until recently, the diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was made on the basis of clinical criteria alone. As a result, prenatal diagnosis has been possible only if sonography disclosed distinct fetal malformations in a subsequent pregnancy. However, the recent description of increased levels of 7-dehydro-cholesterol (cholesta-5,7-dien-3̄-ol) in patients with SLOS, most likely caused by a deficiency of 3β-hydroxysteroid-Δ7-reductase, has provided an apparently reliable biochemical marker for diagnosis of SLOS. To determine if this abnormality of sterol metabolism has utility for prenatal diagnosis of SLOS, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLOS was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7-dehydrocholesterol in plasma. Quantitative analysis by gas chromatography of sterols extracted from the amniotic fluid of both pregnancies revealed similar, markedly increased levels of 7-dehydrocholesterol and its precursor, lathosterol (cholest-7-en- 3β-ol), both of which were undetectable in reference amniotic fluids. These findings suggest that abnormalities of cholesterol biosynthesis in SLOS may be sufficiently expressed in fetal life to permit prenatal diagnosis of this disorder by measurement of 7-dehydrocholesterol in amniotic fluid.

Original languageEnglish (US)
Pages (from-to)272-275
Number of pages4
JournalAmerican Journal of Medical Genetics
Volume56
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

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Smith-Lemli-Opitz Syndrome
Amniotic Fluid
Prenatal Diagnosis
Cholesterol
Sterols
Pregnancy
Hydroxysteroids
Intellectual Disability
Gas Chromatography
Ultrasonography
Oxidoreductases
Biomarkers

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Smith-Lemli-Opitz syndrome : Prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid. / Rossiter, Judith P.; Hofman, K. J.; Kelley, R. I.

In: American Journal of Medical Genetics, Vol. 56, No. 3, 1995, p. 272-275.

Research output: Contribution to journalArticle

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