Smith-Lemli-Opitz syndrome

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Smith-Lemli-Opitz syndrome
Classification and external resources
7-Dehydrocholesterol
ICD-10	Q87.1
ICD-9	759.89
OMIM	270400
DiseasesDB	12223
eMedicine	ped/2117
MeSH	D019082

Smith-Lemli-Opitz syndrome (also SLOS, or 7-dehydrocholesterol reductase deficiency) is a metabolic and developmental disorder that affects many parts of the body.

Presentation

This condition is characterized by distinctive facial features, small head size (microcephaly), mental retardation or learning disabilities, and behavioral problems. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly).

Genetic prevalence

Smith-Lemli-Opitz syndrome has an autosomal recessive pattern of inheritance.

Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 40,000 births. It is most common in Caucasians of European ancestry, but very rare among African and Asian populations.

This disorder is inherited in an autosomal recessive pattern, which means two copies of the gene must be inherited to have the disorder.

Mutations in the DHCR7 gene cause Smith-Lemli-Opitz syndrome. The DHCR7 gene makes an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the production of cholesterol. Cholesterol is an essential nutrient that is necessary for normal embryonic development. Cholesterol is also a structural component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays an important role in the production of certain hormones and digestive acids.

Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome.

Notable cases

On July 24th, 2007, a jury awarded a Florida couple, Daniel and Amara Estrada, whose sons are afflicted with Smith-Lemli-Opitz syndrome, 21 million dollars in damages. The Estradas claimed that a geneticist failed to diagnose their first son's genetic disorder, leading to their having another son with the same disorder.^[1]

References

See also

• David Weyhe Smith

 This article incorporates public domain material from the United States National Library of Medicine document "Genetics Home Reference".

External links

• Richard I. Kelley on SLOS
• Overview of condition at NLM Genetics Home Reference
• GeneReview/UW/NIH on Smith-Lemli-Opitz syndrome