Prenatal diagnosis of holoprosencephaly associated with Smith–Lemli–Opitz syndrome (SLOS) in a 46,XX fetus

Abstract Objective To show the importance of measuring cholesterol precursor levels in amniotic fluid in all pregnancies with ultrasound features (such as holoprosencephaly) suggestive of Smith–Lemli–Opitz syndrome (SLOS), after exclusion of chromosomal anomalies. Case report A 28-year-old woman, gravida 1 para 0, performed chorionic villus sampling for fetal karyotyping at 13 weeks of gestation due to positive combined first trimester screening in a fetus with increased nuchal translucency and suspected holoprosencephaly. The result was normal – 46,XX. The diagnosis of alobar holoprosencephaly was confirmed at 15 weeks of gestation, and cardiac and limb defects were also identified. Thus, a syndromic cause was considered, specifically a chromosomal microdeletion syndrome or a monogenic entity such as SLOS. The latter was confirmed by measuring 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) in amniotic fluid. Molecular analysis of DHCR7 gene identified a homozygous mutation in intron 8, c.964-1G>C, providing molecular confirmation for this diagnosis. Conclusion The differential diagnosis of holoprosencephaly is broad. Identification of the cause of holoprosencephaly aids in establishing the prognosis and is essential to ascertain the mode of inheritance for adequate genetic counseling.