Smith-Lemli-Opitz syndrome

What Is Smith-Lemli-Opitz Syndrome?

Smith-Lemli-Opitz syndrome (SLOS) is an inherited condition in which the body's ability to make cholesterol is impaired due to deficiency of the 7-dehydrocholesterol reductase enzyme. It is caused by mutations in the DHCR7 gene. Cholesterol is critical for the structure of cells and is necessary for the normal development of a baby. Because of this, babies with SLOS often have birth defects. Cholesterol also plays an important role in the production of hormones and digestive acids. In addition to low cholesterol levels, SLOS also causes toxic byproducts of cholesterol production to build up throughout the body, further disrupting growth and development. The severity and types of symptoms can vary from individual to individual.

In children with little or no ability to make cholesterol, symptoms are severe. Some common birth defects in babies with SLOS are an abnormally small head (microcephaly), cleft palate, heart defects, and abnormal genitalia in male infants. They often have difficulty feeding because they lack the sucking reflex and have weak muscle tone. Some have extra fingers or toes as well as fused second and third toes on both feet, which is typical of SLOS. Infants with the severe form of SLOS grow slowly, and most have moderate-to-severe intellectual and developmental disabilities. Severely affected infants may also have problems with their kidneys, which can be life-threatening.

Some children have a milder form of the condition in which the body can produce some cholesterol. Symptoms may include developmental delays, toe defects, slow growth, and short stature. These children generally learn to walk and talk and can acquire other skills, although most do not become independent adults. Aggression is common in adults with SLOS. Sensitivity to sunlight (photosensitivity) is common in people with SLOS.

How Common Is Smith-Lemli-Opitz Syndrome?

SLOS affects an estimated 1 in 20,000 to 1 in 60,000 people. This disease is more common in those of European ancestry, especially in people from Slovakia and the Czech Republic. SLOS syndrome is rare among people of African and Asian descent.

How Is Smith-Lemli-Opitz Syndrome Treated?

There is no cure for SLOS, but some symptoms can be addressed. The primary treatment is to supplement the patient's diet with large amounts of cholesterol, either in the form of purified cholesterol or in the form of food such as egg yolks and cream. This has been shown to improve symptoms.

Early intervention and therapy help with speech and physical disabilities. Medication may treat symptoms such as vomiting, constipation, and gastroesophageal reflux. Surgery can often repair birth defects. Orthotics can help muscle spasms and improve mobility. Additional symptoms are treated as they arise.

Because the condition can cause extreme sun sensitivity, people with SLOS should try to stay out of the sun for long periods of time and should always wear sunscreen, sunglasses, and appropriate clothing when they go outdoors.

What Is the Prognosis for a Person with Smith-Lemli-Opitz Syndrome?

Although serious internal malformations can lead to early death, many people with SLOS can have a normal lifespan with good nutrition and medical care. Intellectual and developmental disabilities typically prevent people with this disease from living independently.