Smith-Lemli-Opitz | RSH Syndrome Overview

What is Smith-Lemli-Opitz syndrome (SLOS)?

SLOS is a metabolic disorder caused by a mutation in the DHCR7 (7-dehydrocholesterol reductase) gene on chromosome 11. This gene codes for an enzyme that is involved in the production of cholesterol. People who have SLOS are unable to make enough cholesterol to support normal growth and development.

Cholesterol is an essential component of the cell membrane and tissues of the brain. A person who can’t make enough cholesterol will therefore experience poor growth, developmental delays, and mental retardation. People with this disorder may also have a range of physical malformations (such as extra fingers or toes) and problems with internal organs (such as the heart or kidney).

How do people get SLOS?

SLOS is inherited in an autosomal recessive pattern. Because it is recessive, a child will not have the symptoms of the disorder unless both parents pass on a defective copy of the DHCR7 gene. This can only happen if both parents are carriers. A carrier is a person who has one good copy and one mutated copy of the DHCR7 gene, but does not experience any symptoms of the disorder. If both parents are carriers, each of their children will have a 25 percent chance of inheriting the disorder.

What are the symptoms of SLOS?

Symptoms vary from person to person, depending upon the amount of cholesterol they can produce. In addition to mental retardation and poor growth, common physical signs of SLOS are a cleft palate (a split upper lip), malformed genitals (in males), and polydactyly (extra fingers or toes).

Other symptoms that may be present at birth include: microcephaly (small head), webbing between the second and third toes, drooping eyelids, heart defects, hearing or sight loss, and difficulties feeding.

With the right medical care and proper diet a person with SLOS can experience a normal life expectancy, although independent living is unlikely due to mental retardation. Sadly, children with the most severe cases of SLOS (produce almost no cholesterol) often die a few months after birth.

How do doctors diagnose SLOS?

An ultrasound (a machine that uses sound waves to look inside a mother’s uterus) can reveal the hallmark physical deformities before a baby is born. Amniocentesis and chorionic villus sampling (CVS) can also determine whether the baby will be born with SLOS.

After birth, a blood test can determine whether someone has the disorder. The test looks for low levels of cholesterol, as well as higher-than-normal levels of a precursor of cholesterol.

How is SLOS treated?

There is no cure for SLOS. Cholesterol therapy, which comes in several forms and can improve growth and development, is the recommended treatment. The results, however, vary and not every family sees significant change. Other possible treatments such as simvastatins and antioxidants are currently being investigated through clinical trials. Surgery may be necessary to correct some of the physical deformities (cleft palate, heart defects) associated with the disorder.

Interesting facts about SLOS

  • In the United States, about 1 out of every 20,000 babies is born with SLOS.
  • The prevalence of carriers is thought to be as high as 1 in 30 in some populations.
  • SLOS was initially named RSH, for the initials of the first three patients diagnosed with the disorder. It was later changed to honor the three geneticists (David Smith, Luc Lemli, and John Opitz) who first described the disorder in 1964.