Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive congenital genetic disorder involving a defect in the DHCR7 gene, which is involved in cholesterol metabolism, that results in abnormalities in a wide range of body systems. This disorder is characterized by pre- and postnatal growth retardation, microcephaly, moderate to severe cognitive impairment, and distinctive facial features. Malformation in multiple organ systems including the brain and central nervous system (CNS), lungs, heart, and genitourinary and gastrointestinal tracts is common.

The signs and symptoms of SLO syndrome can vary widely from patient to patient, from minor cognitive impairment with minor congenital malformation to severe intellectual impairment with major life-threatening abnormalities. Microcephaly may be present, and facial features may include a high-arched palate, cleft lip / palate, short nasal root with a broad base and nasal bridge, anteverted nares, blepharoptosis, a small chin, micrognathia, and low set and posteriorly rotated ears. Many patients have polydactyly or syndactyly of the hands and feet, with a syndactyly of the second and third toes seen most often. Cognitive and intellectual disabilities can range from low normal intelligence to profound intellectual disability. Most patients display autistic behaviors and are prone to self-injurious behaviors. CNS abnormalities can include a small frontal lobe, cerebellar hypoplasia, ventriculomegaly, and agenesis of the corpus callosum. Ambiguous genitalia and congenital heart disease are common.

The diagnosis of SLO syndrome can be made prenatally by measuring 7-dehydrocholesterol (7DHC):total sterol ratio in a chorionic villus sampling (CVS) taken at 11-12 weeks of gestation or by detecting increased 7DHC in the amniotic fluid at 13 weeks' gestation. Postnatal diagnosis can be made if the patient has the characteristic physical features with a high plasma 7DHC level.

SLO syndrome is the second most common recessive genetic disorder found at a frequency of 1:20 000 to 1:40 000.