Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (also SLOS, or 7-dehydrocholesterol reductase deficiency) is an autosomal recessive metabolic and developmental congenital disorder that causes the inability to correctly produce or synthesize cholesterol due to a low occurrence of the 7-DHC reductace enzyme.

Symptoms
The signs and symptoms of SLOS syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual and physical disabilities. Common symptoms are: SLOS is also linked to autism
 * Small head size (microcephaly)
 * Mental retardation
 * Learning disabilities and behavioral problems
 * Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia
 * Hypocholesterolemia
 * Paleness
 * Low muscle tone (hypotonia)
 * Delayed development and speech
 * Feeding difficulties
 * Drooping eyelids (ptosis)
 * Cataracts
 * Hirschsprung disease
 * Hearing impairment
 * Weak immune system
 * Scoliosis
 * Osteoporosis
 * Fused second and third toes (syndactyly)
 * Extra fingers or toes (polydactyly)

Genetic prevalence


Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 40,000 births. It is most common in Caucasians (especially Scandinavians) 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. It is estimated that as many as 1 in 30 people are carriers for the syndrome.

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.

Autism
SLOS is believed to have a relation to autism. Studies have shown up to 86% of children with SLOS also had autism.

Diagnosis
There are two ways to test for SLOS. A specialized blood test to measure the level of 7-DHC or a lipid panel are the most common tests. The second way to test is to have molecular testing (also known as DNA testing) done to look for the known SLOS mutations.

Treatment
SLOS can be treated by taking cholesterol either in synthetic form, or via natural foods such as egg yolk and cream, or a combination of both.