Smith-Lemli-Opitz Syndrome (SLOS)
What is Smith-Lemli-Opitz Syndrome?
Smith-Lemli-Opitz Syndrome (SLOS) is an inherited disorder in which affected individuals are deficient in their ability to make cholesterol. Cholesterol is important in maintaining the normal functions of cells and nerves. It also plays a role in early human development.
The signs and symptoms of SLOS can be different from person to person. Most individuals with SLOS have birth defects and intellectual disability. Mildly affected individuals may only have subtle learning disabilities and physical abnormalities. whereas severely affected individuals may have many of the features listed below:
Common features include:
- Small head size
- Intellectual disability and/or learning difficulties
- Hearing loss
- Eye abnormalities (cataracts and ptosis of eyelids)
- Feeding difficulties
- Cleft palate
- Poor growth and appetite
- Heart defects
- Breathing difficulties
- Polydactyly (extra fingers and toes)
- Underdeveloped or ambiguous external genitalia
- Webbed toes
How many people have Smith-Lemli-Opitz Syndrome?
It is estimated that approximately 1 in 20,000 babies are born with SLOS. SLOS has been found more frequently in Whites, African Americans and Hispanics, and less frequently in Asians. Males and females are equally affected.
What causes Smith-Lemli-Opitz Syndrome?
SLOS is caused by a mutation or change in a gene. Genes are units of DNA, our bodies' instruction manuals for growth and development, and are inherited from our mother and father at conception. In SLOS, the gene that has been changed or mutated is called the DHCR7 gene (DHCR7). This gene is responsible for making the enzyme 7-dehydrocholesterol reductase. This enzyme is needed to carry out the final step of cholesterol production in our bodies, converting 7-dehydrocholesterol (7DHC) to cholesterol. Mutations or changes in the DHCR7 gene prevent the body from making the cholesterol that it needs. This also leads to a buildup of 7DHC in the body, since it is unable to be converted to cholesterol normally.
SLOS is an inherited autosomal recessive disorder. Affected individuals inherit two copies of the mutated or changed gene, one from each parent. Therefore the parents are "carriers" of SLOS, meaning that they have one normal functioning copy and one non-functioning copy of the DHCR7 gene. With each pregnancy, carriers of SLOS have a 1 in 4 or 25% chance of having a child with SLOS.
How is Smith-Lemli-Opitz Syndrome diagnosed?
SLOS is typically diagnosed by a blood test that measures the amount of cholesterol and 7-dehydrocholesterol (7DHC) in the blood. Since individuals with SLOS have a lowered capacity to make cholesterol, we expect cholesterol levels to be low and 7DHC level to be high. However, in some cases, cholesterol levels can be in the normal range. Genetic testing can also be done to identify the specific changes in the DHCR7 gene that cause SLOS in that particular individual. When this information is known, testing other family members and prenatal testing in future pregnancies is also available.
What is/is there treatment for Smith-Lemli-Opitz Syndrome?
There is currently no proven treatment for SLOS. Many individuals are given cholesterol supplementation or a high cholesterol diet, and others take simvastatin. Simvastatin has not been proven to be effective and is still considered investigational therapy that normally is not prescribed in SLOS outside of a research protocol.