Genetics Northern California

Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic disorder that causes mental retardation, poor growth and birth defects. SLOS occurs in 1 out of 100,000 to 1 out of 130,000 births. SLOS is an inborn error of metabolism that is caused by a genetic defect in the ability to make cholesterol, an essential nutrient for normal growth and development. All babies require cholesterol even before birth to help their brain and body develop.

Individuals with SLOS typically have very low levels of cholesterol and very high levels of cholesterol precursors in their blood. The infants with the lowest cholesterol levels tend to have the most severe forms of the disorder and often die at birth or in the first few months of life.

In addition to growth retardation and developmental delay, many different malformations have been described in SLOS. The most common malformations are microcephaly, low-set ears, small, upturned nose, cleft palate, cataracts, blepharoptosis, micrognathia, short thumbs, extra fingers or toes, abnormal palmar creases (usually single), webbing between 2nd and 3rd toes, hypospadias, undescended testicles, heart defects, pyloric stenosis and Hirschsprung disease. Some children will have only one or two minor malformations and others will have almost all of the defects listed above. Children born with this condition may die in infancy or live to adulthood. No one can predict how long someone with SLOS will live, because it depends on the severity of their medical problems. Some are severely affected, a few are mildly affected, but most are somewhere in the middle.

Infants with SLOS usually have feeding problems and poor growth. Common feeding problems include trouble sucking and swallowing because of weakness, cleft palate, microgastria, reflux, persistent vomiting, and pyloric stenosis. Other causes of poor growth may be internal malformations such as heart and kidney defects, Hirschsprung disease, or more rarely, chronic liver disease. However, even children who are vigorous and feed well do not grow normally and tend to be small as children and adults. Many patients will need to be fed with a gastrostomy feeding tube.

Babies with SLOS cannot make enough cholesterol because two important genes that make cholesterol do not work correctly. Genes occur in pairs, one gene from each pair comes from the mother and the other gene comes from the father. If both parents have one "non-working" cholesterol gene and one working cholesterol gene, they are known as "carriers". Carriers have normal amounts of cholesterol themselves, but if the baby inherits the non-working gene from both parents, the baby cannot make cholesterol normally. Only children who inherit two non-working copies of the gene will have SLOS. There is a 1 in 4 or 25 percent chance that two carrier parents will have a baby with SLOS.

The diagnosis of SLOS is made by demonstration of elevated levels of cholesterol precursors in the blood after birth. Prenatal diagnosis by amniocentesis or chorionic villus sampling (CVS) is also available. The gene for SLOS has been localized to the long arm of chromosome 11 and many different mutations have been identified within the gene in affected patients.

There is no way to replace the non-working gene at this time, so each problem caused by SLOS needs to be treated separately. There is no treatment at this time that will eliminate all of the problems that an individual with SLOS has. Supplementation of the diet with cholesterol, either as a natural food source (egg yolks) or giving it directly as medication has been shown to improve some of the development and growth problems in some patients. However, this does not cure or reverse the mental retardation and birth defects associated with SLOS.


Genetic Science Learning Center: Smith-Lemli-Opitz Syndrome - Good general information site about SLOS.

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.