Smith-Lemli-Opitz syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 8, 2016
StartDiseasesSmith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a congenital disorder (present at birth) that causes an error in how the body manufactures cholesterol. Like many other congenital conditions, SLOS can present with a variety of signs and symptoms that can range from barely noticeable facial defects to major intellectual disabilities and behavioral problems.


Definition & Facts

SLOS is the result of a defective enzyme that forms the final link in the biochemical chain of events that produces cholesterol. Although the word “cholesterol” is often associated with something that most people wish they had less of, cholesterol is one of the building blocks of numerous substances that are critical to the normal function of the body such as hormones, digestive enzymes, and even vitamin D.

Since production of this enzyme is under the control of a single defective gene, this defect is present from the earliest stages of embryonic development. The gene is inherited in an autosomal recessive inheritance pattern, meaning that both parents must possess the defective gene before it can be passed on to offspring.

Symptoms & Complaints

The mechanisms by which SLOS exerts its effects on the developing embryo, and later the fetus, is not well understood. What is known is that the signs and symptoms of SLOS can represent a constellation of physical defects and/or neuropsychological problems that can vary from the hardly noticeable to life-threatening.

The “classic” or “textbook” cases of SLOS will include a number of physical signs such as microcephaly (an abnormally small skull, a condition that is also associated with the Zika virus and with fetal alcohol syndrome), abnormally placed ears, and reduced muscle tone that may lead to difficulty nursing and failure to thrive.

Malformations of the heart, gastrointestinal tract, and genitourinary system are also frequently present. From a neuropsychological standpoint those suffering from SLOS may exhibit learning and social adaptation disorders that are similar to those seen in autism spectrum disorder.

People with this syndrome may also have polydactyly in which they have extra fingers or syndactyly in which their fingers are webbed or fused together.


As noted earlier in this article, the direct cause of SLOS is a defective enzyme that is essential for the manufacture of cholesterol. Estimates of the number of infants born with SLOS vary, with most authorities accepting a value of between 1 in 20,000 and 1 in 60,000 births. SLOS is seen more frequently in caucasians of central European ancestry (e.g. Czech Republic and Yugoslavia) and is rare among those of African or Asian descent.

Diagnosis & Tests

Since SLOS is characterized by a number of physical abnormalities such as microcephaly, congenital heart defects, and malformed facial features the presence of any of these in the newborn is sufficient reason to begin a full genetic workup. If, however, the major physical abnormalities are absent or not as severe as those seen in the “classic” cases of SLOS, the diagnosis may be delayed until the infant fails to meet expected growth and developmental criteria.

Certain symptoms can be detected during prenatal ultrasound. However, unless the ultrasound examination takes place in the late second or early third semester, when the body parts are closer to their birth size, even the more obvious defects could be missed.

If pathology is detected by ultrasonography or a family history of SLOS is present, an amniocentesis may be conducted which would test for the genetic mutations associated with this syndrome. Another prenatal diagnostic technique is chorionic villus sampling which involves taking a sample of the placenta and testing it. This test may reveal elevated levels of a cholesterol precursor called 7DHC, which is also seen in SLOS.

Treatment & Therapy

Treatment and therapy of the infant with SLOS must be individualized and is guided by the infant’s clinical condition. SLOS is an inherited condition, and there is currently no drug or other treatment that can repair the genetic defect responsible for SLOS. Instead, treatment involves addressing issues discovered by the immediate post-natal physical examination.

The management of SLOS begins with the surgical repair of any life-threatening birth defects (such as congenital heart defects) and is followed by symptomatic management of other issues as they arise.

Since infants and children with SLOS will invariably have at least some degree of intellectual disability, placement in a special education program from an early age will usually be necessary. As previously noted, children with SLOS will have behavioral and social adjustment issues similar to those seen in autism spectrum disorder and will usually benefit from educational programs that are tailored to the needs of such children and adolescents.

Prevention & Prophylaxis

As mentioned several times in previous sections of this article, there is no intervention that can prevent SLOS. This has instead focused treatment, prevention and prophylaxis efforts to minimize the effects of the condition, particularly to growth and development issues as well as the intellectual disabilities that are the hallmark of SLOS.

Since SLOS is caused by a disorder of cholesterol production, this has led to the creation of dietary regimens that focus on increasing cholesterol intake to compensate for the body’s failure to produce that substance. Such diets have been reported to be successful, in varying degrees, in reducing the degree of growth retardation that accompanies SLOS.