Rare multiple congenital malformations/developmental disorders are challenging in clinical diagnosis. The introduction of next-generation sequencing (NGS) has revolutionized this diagnostic by offering multigene panels or whole-exome sequencing. However, if there is no possibility to perform NGS or if we are facing prenatal ultrasound results, clinical diagnostics is even more difficult. For a selected group of congenital metabolic disorders, resulting from defects in cholesterol biosynthesis (called cholesterolopathies), application of gas chromatography-mass spectrometry (GS-MS) may provide or orientate diagnostics. The most common of these is Smith-Lemli-Opitz syndrome (SLOS), but in this publication, we also want to introduce other cholesterolopathies and draw attention to the possibility of non-invasive prenatal diagnosis of SLOS.
Keywords: GC-MS; Smith-Lemli-Opitz; cholesterol biosynthesis; prenatal diagnosis; prenatal ultrasound.