Smith–Lemli–Opitz syndrome

Smith–Lemli–Opitz syndrome is an autosomal recessive disorder caused by pathogenic variants in DHCR7, which impair the final step of cholesterol synthesis. It can cause congenital anomalies, developmental differences, and elevated 7-dehydrocholesterol.

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7-Dehydrocholesterol: A sterol that is converted into cholesterol by the enzyme 7-dehydrocholesterol reductase. Its accumulation is the biochemical hallmark of impaired DHCR7 activity.
Smith–Lemli–Opitz syndrome diagnosis: The process of identifying Smith–Lemli–Opitz syndrome through clinical findings, sterol analysis, and genetic testing. Elevated 7-dehydrocholesterol and DHCR7 variants help confirm the diagnosis.
Autosomal recessive inheritance: An inheritance pattern in which a condition generally occurs when both copies of a gene carry disease-causing variants. A child typically develops the syndrome after inheriting a pathogenic DHCR7 variant from each parent.
Polydactyly: The presence of extra fingers or toes. Postaxial polydactyly is a characteristic feature in some affected individuals.
7-Dehydrocholesterol reductase: The enzyme that catalyzes the final step of cholesterol biosynthesis, converting 7-dehydrocholesterol into cholesterol. DHCR7 encodes this enzyme, whose reduced activity drives the disorder.
Sterol analysis: Laboratory measurement of sterols and related compounds in biological samples. Measuring 7-dehydrocholesterol can reveal the pathway defect.
Congenital anomaly: A structural or functional difference that is present at birth and arises during development. The syndrome can affect multiple structures as they form before birth.
Syndactyly: The congenital joining of two or more fingers or toes. Fusion of the second and third toes is a frequent clinical clue.
Cholesterol biosynthesis: The sequence of cellular reactions that produces cholesterol from smaller molecules. The syndrome disrupts its final enzymatic step.
DHCR7: A gene that encodes 7-dehydrocholesterol reductase and is associated with Smith–Lemli–Opitz syndrome when both copies carry pathogenic variants. Testing DHCR7 can establish the molecular cause and support family testing.