Genetics Northern California

Smith-Lemli-Opitz Syndrome

What is Smith-Lemli-Opitz syndrome (SLOS)?
How common is Smith-Lemli-Opitz?
What causes Smith-Lemli-Opitz?
How is Smith-Lemli-Opitz diagnosed?
Can Smith-Lemli-Opitz be diagnosed during pregnancy?
How is Smith-Lemli-Opitz treated?
Where can I get more information about Smith-Lemli-Opitz?

What is Smith-Lemli-Opitz syndrome?
Smith-Lemli-Opitz syndrome (SLOS) is an inherited condition that can affect many parts of the body and may also include learning and behavior issues. The severity of the condition can vary, even in the same family. Individuals with a mild form of SLOS may only have slight differences in appearance, low muscle tone, and normal or near-normal learning. Individuals with the more severe form of SLOS may have life-threatening health problems at birth.

Medical concerns in SLOS 
Many different medical concerns are seen with this condition. Severe SLOS often includes:
Poor growth (before and after birth)
Changes in brain formation
Cleft palate (an opening in the roof of the mouth)
Heart defects
Underdeveloped genitals (in males)
Feeding and swallowing problems
Intestinal problems
Extra fingers or toes

Learning and behavior in SLOS
There is a wide range of learning abilities in individuals with this condition. Learning is usually delayed, but can vary from mild delays to more significant delays. Behavior concerns are common and may include autistic behaviors, aggressiveness, and self-harm. Despite these concerns, most parents report their children as loving, affectionate and happy.

How common is SLOS?
It is estimated that one in every 20,000 newborns worldwide has SLOS. However, it may be more common than that. The features of this condition are extremely variable, so the diagnosis may be missed in some newborns. Both males and females can have SLOS.

What causes SLOS?
Individuals with SLOS have low levels of an enzyme called 7-dehydrocholesterol (7-DHC). This enzyme is important for making cholesterol in the body. Babies need cholesterol even before birth to help their brain and body develop. Humans inherit two copies of the gene that makes 7-DHC (one from each parent). The gene is called DHCR7. A person with SLOS has a genetic change (mutation) in both copies of the DHCR7 gene, so they are unable to make enough enzyme for normal development.

SLOS is inherited as a recessive condition. That means both parents are silent carriers of a DHCR7 gene that is not working. For carrier couples, there is a 1 in 4 (25%) chance in each pregnancy that the baby will get two non-working copies of the gene (one from each parent). This causes SLOS.

How is SLOS diagnosed?
The diagnosis may be suspected when a person has features commonly seen in SLOS. The diagnosis is confirmed by measuring the amount of 7-DHC enzyme in the blood. Testing can also be done by measuring cholesterol values from a blood sample. However, cholesterol testing is not as reliable as the enzyme test. Most people with SLOS have very low levels of cholesterol, but the values can sometimes fall in the normal range and cause the diagnosis to be missed.

Can SLOS be diagnosed during pregnancy?
SLOS can be diagnosed during pregnancy when the gene mutations in the family are known or when the diagnosis is suspected from a prenatal screening test. A sample from the developing baby can be taken by CVS or amniocentesis. Then, special testing is ordered to measure the 7-DHC enzyme levels or to look for mutations in the DHCR7 gene.

Prenatal screening tests can look for signs of SLOS, but screening tests will miss some cases. The California Prenatal Screening Program uses blood samples from pregnant women to screen for SLOS. In addition, prenatal ultrasound may find birth defects that could be part of SLOS, such as heart defects. A diagnostic test would still be needed to confirm the diagnosis.

How is SLOS treated?
Treatment may include a high cholesterol diet. However, it is unclear if adding cholesterol to the diet helps improve development and growth. Currently, there is no proven treatment for SLOS. There are clinical trials studying other possible treatments. Medical care is arranged based on individual need and could involve many different specialists. Surgery may be needed to repair some birth defects.

Where can I get more information about Smith-Lemli-Opitz? 

Genetics Home Reference: Smith-Lemli-Opitz syndrome - General information about SLOS provided as a service of the U.S. National Library of Health. Also includes links to many related sites.
Smith-Lemli-Opitz/RSH Foundation - This website provides detailed information about SLOS and many different resources for families.

Last reviewed: December 21, 2017

Last updated: December 21, 2017

Reviewed by: Kimberly Barr, MS, LCGC