Smith-Lemli-Opitz Syndrome

What is Smith-Lemli-Opitz syndrome?

Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterised by distinctive facial features, small head size (microcephaly), mental retardation or learning disabilities, and behavioural 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).

The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioural problems. Severe cases can be life-threatening and involve profound mental retardation and major physical abnormalities.

How common is Smith-Lemli-Opitz syndrome?

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

What genes are related to Smith-Lemli-Opitz 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 a fat-like substance that is found in some foods and is also produced by the body. It 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.

How do people inherit Smith-Lemli-Opitz syndrome?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for Smith-Lemli-Opitz syndrome?

• 7-Dehydrocholesterol reductase deficiency
• RSH Syndrome
• SLOS
• SLO syndrome