> SLOS

• Symptoms & Characteristics
• Treatment
• How Common Is It?
• Genetics & Inheritance
• Genetic Testing
• Support & More Information
• Alternative Names

Last Reviewed June 2, 2009

Symptoms & Characteristics

Smith-Lemli-Opitz syndrome (commonly called SLOS) is a genetic condition that affects various parts of the body. People affected with SLOS cannot make cholesterol, which is an essential nutrient that has important functions both before and after birth. Common characteristics and symptoms may include:

• distinctive facial features

• small head size (microcephaly)

• mental retardation/developmental delay or learning disabilities

• behavioral problems

• autism

• congenital defects of heart, lungs, kidneys, gastrointestinal tract, and genitalia

• low muscle tone (hypotonia)

• feeding difficulties

• growth retardation

• fused second and third toes (syndactyly)

• extra fingers or toes (polydactyly)

• abnormal urethral opening on male penis (hypospadias)

• opening in roof of the mouth (cleft palate)

The signs and symptoms of SLOS vary greatly. Mildly affected people may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve severe mental retardation and major physical defects. 

Treatment

There is no cure for SLOS. In some cases, early diagnosis, routine surveillance and treatment can help to manage some of the symptoms and sometimes prevent related problems.

How Common Is It?

About 1 in 20,000 to 1 in 40,000 newborns are believed to be affected with SLOS.

Genetics & Inheritance

SLOS is caused by mutations in a gene called DHCR7, which is located on chromosome 11 at the location q13.2-q13.5.

• There are over 70 identified mutations in the gene, but three specific mutations are the most common.

• The DHCR7 gene provides instructions for making an enzyme called 7-dehydrocholesterol reductase (DHCR7), which is responsible for the final step in the production of cholesterol. Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol reductase, preventing cells from producing enough cholesterol.

We all have two copies of the DHCR7 gene - one from each parent. In SLOS, it is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.

• Both parents of an affected person are always obligate carriers (each have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but typically do not have symptoms themselves.

• Without a family history, the chance to be a carrier is determined by a person's ethnic background. For example, SLOS is most common in Caucasians of European ancestry, particularly people from Central European countries such as Slovakia and the Czech Republic. SLOS is very rare among African and Asian populations.

There are other genetic conditions that have features which overlap with SLOS. Some of these conditions include Trisomy 13, Trisomy 18, and Noonan syndrome.

A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.

Genetic Testing

Clinical genetic testing for Smith-Lemli-Opitz syndrome can be broken down into two categories: diagnostic testing and carrier testing.

• Diagnostic testing may be used to confirm or rule out a clinical diagnosis in a person suspected to have the disorder. A clinical diagnosis is often made by special biochemical testing that looks for elevated 7-dehydrocholesterol levels and/or an elevated 7-dehydrocholesterol:cholesterol ratio.

• Carrier testing is typically offered after a clinical diagnosis and/or mutations have already been identified in an affected family member(s). Carrier testing usually involves DNA testing for the known familial mutations or if not available, the most common mutations. Biochemical testing cannot be used for carrier testing purposes.

Clinical genetic testing for Smith-Lemli-Opitz syndrome is available through an in person genetic consultation for people who are considered at risk. Use our find a professional directory to locate a trained genetic professional in your area.

• A medical geneticist can also be found at the American College of Medical Genetics website.

• A genetic counselor can also be found at the National Society of Genetic Counselors website.

Support & More Information

More information can be found at:

• Genetics Home Reference

Support can be found at:

• Smith-Lemli-Opitz/RSH Foundation

Alternative Names

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