Assessing Postnatal Mortality in Smith–Lemli–Opitz Syndrome

Abstract

ABSTRACTSmith–Lemli–Opitz syndrome (SLOS) is a rare autosomal recessive disorder caused by pathological variants in DHCR7, resulting in a deficiency in the enzyme 7‐dehydrocholesterol reductase. This results in elevated levels of cholesterol precursors and typically low cholesterol levels, leading to a range of physical and cognitive challenges. Mortality rates in infants with severe SLOS are high, due to congenital malformations. Premature death has been described in individuals with SLOS, particularly in severely affected individuals. Further research is needed to understand postnatal mortality risk factors for individuals with SLOS. Understanding these factors could improve monitoring and prevention efforts. To investigate this, we obtained death certificates from the National Death Index (NDI) database on a cohort of individuals with SLOS who were enrolled in natural history studies at the National Institutes of Health Clinical Center (NCT00001721 and NCT05047354). Analysis and comparison of this deceased cohort showed that although premature death occurs in SLOS, many individuals with SLOS survive into adulthood. We also observed the risk of postnatal mortality increasing with higher severity scores and lower initial cholesterol levels.Trial Registration: NCT00001721 and NCT05047354.