Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide and individuals have been described with normal development and only minor malformations.
The diagnosis of SLOS relies on clinical suspicion and detection of elevated serum concentration of 7-DHC. Although serum concentration of cholesterol is usually low, it may be in the normal range in approximately 10% of affected individuals, making it an unreliable test for screening and diagnosis. DHCR7 is the only gene in which mutation is known to cause SLOS. Sequence analysis of DHCR7 detects approximately 96% of known mutations.
SLOS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier detection is possible if the disease-causing mutations in the family are known. Prenatal testing for pregnancies at risk is possible using biochemical testing or molecular genetic testing if the disease-causing mutations in the family are known.