Smith-Lemli-Opitz Syndrome (SLOS) is a severe developmental disorder. The clinical spectrum is wide and includes both pre- and post-natal growth retardation, mild to severe mental retardation, multiple congenital malformations (both major and minor), and characteristic facies. Frequent additionally observed findings include: microcephaly, micrognathia, cleft palate, cardiac defects, abnormal external genitalia, post-axial polydactyly, and 2-3 toe syndactyly. Infants are often hypotonic with poor suck, and have failure to thrive. Older children commonly have behavioral concerns including autism, hyperactivity, aggression, and self-injurious behavior.
Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and low levels of serum cholesterol. In cholesterol biosynthesis, 7-DHC is converted to cholesterol by the enzyme 3b-hydroxysterol D7-reductase (sterol delta-7-reductase), which is encoded by the gene DHCR7. DHCR7 is also required to reduce 7-dehydrodesmosterol to desmosterol. Mutations in the DHCR7 gene underlie SLOS.