Smith-Lemli-Opitz Syndrome

Key Features

• Elevated 7- and 8-dehydrocholesterol in serum is diagnostic in Smith-Lemli-Opitz (SLO) syndrome, which presents with developmental delay and malformations

• Chondrodysplasia punctata, skin defects, and neurologic symptoms can indicate other cholesterol synthetic defects

• An autosomal recessive disorder caused by a deficiency of the enzyme 7-dehydrocholesterol Δ7-reductase

Clinical Findings

• Microcephaly

• Poor growth

• Mental retardation

• Typical dysmorphic features of face and extremities (particularly two- to three-toe syndactyly)

• Malformations of the heart and genitourinary system

Diagnosis

• Elevated 7- and 8-dehydrocholesterol in serum or amniotic fluid is diagnostic

• Serum cholesterol levels may be low or in the normal range

• Enzymes of cholesterol synthesis may be assayed in cultured fibroblasts or amniocytes, and mutation analysis is possible

Treatment

• Although postnatal treatment does not resolve prenatal injury, supplementation with cholesterol in SLO improves growth and behavior

• The role of supplemental bile acids is controversial