What is Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a rare, genetic metabolic disorder caused by the body's inability to produce enough cholesterol, which is essential for normal growth and brain development. This condition affects multiple body systems and is characterized by a wide range of physical, developmental, and behavioral challenges that vary significantly in severity from person to person.

What causes Smith-Lemli-Opitz syndrome?

Smith-Lemli-Opitz syndrome is caused by mutations in the DHCR7 gene, which provides instructions for making the enzyme 7-dehydrocholesterol reductase. This enzyme is the final step in the body’s cholesterol synthesis pathway. When this enzyme is deficient, the body cannot convert 7-dehydrocholesterol into cholesterol, leading to both a deficiency of cholesterol and a toxic buildup of its precursors. Because cholesterol is a critical building block for cell membranes and the brain, this disruption affects nearly every organ system. Smith-Lemli-Opitz syndrome is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene to pass the condition to their child.

How does Smith-Lemli-Opitz syndrome affect the body?

The clinical presentation of Smith-Lemli-Opitz syndrome is highly variable, ranging from mild learning disabilities to severe, life-threatening complications. Because cholesterol is vital for embryonic development, the condition typically impacts the following areas:

• Physical features: Many infants have a small head size (microcephaly), distinct facial features, and may have webbing of the second and third toes (syndactyly).


• Developmental delays: Intellectual disability and delayed speech development are common.


• Behavioral challenges: Individuals with Smith-Lemli-Opitz syndrome often experience autism-like behaviors, sleep disturbances, and self-injurious actions.


• Organ systems: Structural heart defects, gastrointestinal issues (such as pyloric stenosis), and genital abnormalities are frequently observed.


• Feeding difficulties: Many infants struggle with failure to thrive and require specialized nutritional support.

How common is this condition and who is affected?

Smith-Lemli-Opitz syndrome is considered a rare disease, with an estimated prevalence ranging from 1 in 20,000 to 1 in 60,000 live births in European populations. It appears to be less common in individuals of African or Asian descent. Because it is a recessive genetic disorder, it affects males and females equally, and it is usually diagnosed in the newborn period or early childhood when physical symptoms or growth delays become apparent. Currently, 61 people within the DiseaseMaps.org community have shared their personal experiences with Smith-Lemli-Opitz syndrome, highlighting the diversity of the patient journey.

How is Smith-Lemli-Opitz syndrome distinguished from other conditions?

What differentiates Smith-Lemli-Opitz syndrome from other developmental disorders is the biochemical profile. A diagnosis is confirmed through a blood test that detects low levels of cholesterol and significantly elevated levels of 7-dehydrocholesterol. Unlike many other genetic syndromes that are strictly developmental, Smith-Lemli-Opitz syndrome is a metabolic disorder, meaning some symptoms may be managed through dietary cholesterol supplementation and bile acid therapy, which can sometimes improve growth and behavior.

Next steps

• Consult with a clinical geneticist to confirm the diagnosis through DHCR7 gene sequencing.


• Schedule appointments with a metabolic specialist or endocrinologist to monitor cholesterol levels.


• Connect with the 61 community members on DiseaseMaps.org who are navigating life with Smith-Lemli-Opitz syndrome.


• Engage with early intervention services, including speech, occupational, and physical therapy, to support developmental milestones.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment; always seek the guidance of your physician with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Smith-Lemli-Opitz syndrome overview.


• Orphanet: Rare Disease Database (ORPHA: 3163).


• Online Mendelian Inheritance in Man (OMIM): 270400 (Smith-Lemli-Opitz Syndrome).


• Smith-Lemli-Opitz Syndrome Foundation: Patient support and clinical research resources.