P759: Reassessing Smith–Lemli–Opitz syndrome screening: Reflections from a recent clinical diagnosis

Smith–Lemli–Opitz syndrome (SLOS) is a severe autosomal recessive disorder caused by biallelic pathogenic variants in DHCR7, leading to impaired cholesterol biosynthesis. Affected individuals may present with multiple congenital anomalies, intellectual disability, and a high rate of fetal or neonatal loss. California’s Department of Public Health previously included SLOS in its second-trimester prenatal screening program using maternal serum analytes (AFP, uE3, and hCG). However, after screening more than 770,000 pregnancies between 2002 and 2004, only four confirmed cases were identified in 2,018 screen-positive pregnancies, resulting in a very low positive predictive value.