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Smith Lemli Opitz Syndrome (SLOS)
Monday, 04 August 2003
Monday, 01 August 2005
RSH Syndrome


Smith-Lemli-Opitz Syndrome (SLOS) is a rare, inherited, genetic disorder that affects the development of children both before and after birth. SLOS is characterized by an inability to produce cholesterol in amounts sufficient for normal growth and development. Cholesterol is an important component of cell membranes, a precursor for many hormones and a major component of myelin, the insulating material around nerves that ensures proper signaling and communication throughout the nervous system.


It is estimated that 1 in 20,000 to 60,000 babies in the United States is born with this condition. Similar rates of incidence have been observed in people of Northern European descent and also in Hispanics. SLOS appears to be much less common in African and Asian populations. SLOS is equally prevalent among males and females.

Signs and Symptoms

At birth, these babies are often small for gestational (time spent in the womb) age, may have very poor muscle tone, and/or a distinctive, shrill cry. There are a variety of physical features that may be present and every child with this disease will exhibit different physical characteristics with varying severity. Possible features include a small head, small chin, droopy eyelids, lazy eye, cataracts, low-set ears, conjoined toes, extra digits, cleft palate, heart murmur or respiratory distress related to heart or lung abnormalities. Malformations of the digestive system may also be present and usually symptoms are evident within the first few months of life. Examples of these symptoms include vomiting, feeding problems, constipation, and electrolyte disturbances. Males with this disease may also exhibit a malformation of the penis known as hypospadias or have undescended testicles. Unfortunately, brain development is compromised as a result of the cholesterol deficiency and children usually exhibit some sort of neurological impairment such as behavioral problems, vision or hearing loss and usually some degree of mental retardation. Mildly affected individuals may exhibit only subtle facial malformations and learning disabilities, whereas severely affected individuals may have complete sex reversal, lethal cardiac and brain malformations, cleft palate, and multi-organ system failure. Any of these severe manifestations of the disease may lead to miscarriage during pregnancy, still birth at the time of delivery, or death of the newborn within the first few weeks of life.

Possible Causes

The cholesterol deficiency that patients experience is due to their lacking the 7-Dehydrocholesterol (DHC) reductase enzyme that converts 7-DHC to cholesterol. As with all “inborn errors of metabolism”, the harmful effects observed in patients are either due to the accumulation of toxic precursors and/or by the lack of the missing enzyme’s product. In the case of SLOS, the precursor 7-DHC is potentially toxic in large concentrations and the cholesterol deficiency is almost certainly detrimental. Research has demonstrated that the gene that normally codes for the 7-DHC reductase enzyme is found on chromosome 11 and SLOS is an example of a disease that is inherited in an autosomal recessive pattern. As such, both parents are carriers of an abnormal gene, but show no physical evidence themselves because they have two copies of every gene and the parents’ second copy of the gene is protective. There was no way for the parents to know that they carried a copy of the disease-causing gene until the chance event that they had a child together who was affected. After their child is diagnosed with this disease, parents should be counseled to inform them that subsequent pregnancies will have a 1 in 4 chance of having this disease and prenatal testing is available for early diagnosis.


In families with a previously affected pregnancy, fetal ultrasound may reveal anomalies suggestive of SLOS and the diagnosis can be confirmed by either chorionic villi sampling or amniocentesis. This disorder is usually suspected at birth or shortly thereafter due to the congenital malformations associated with it. However, in some instances the disease is so subtle that children avoid diagnosis until later into childhood or even adulthood. A geneticist will usually perform a number of blood tests to evaluate a patient for possible syndromes. With respect to SLOS, plasma total cholesterol and LDL levels may be low but not always. The confirmatory test looks at the ratio of 7-DHC to cholesterol and an extremely elevated level of 7-DHC establishes the diagnosis. A number of imaging studies and procedures are helpful once a diagnosis is made to see what kinds of internal abnormalities are present. For example, MRI (magnetic resonance imaging) or CT (computed tomography) of the brain, echocardiogram of the heart, hearing tests, eye exams and ultrasounds of the kidneys, abdomen and pelvis to look for renal, digestive and genitourinary problems, respectively, are often obtained.


Cholesterol supplementation is a logical treatment for this disease but long-term research evidence for this is lacking. It has only been about 10 years since the enzyme defect has been identified in this disease and, as a result, there has not been a great deal of research to determine the best methods and doses for supplementation. Many such projects are currently underway. Hormone therapy regimens are also being researched since many hormones in our body are produced from cholesterol. Research projects to try to prevent the development of the potentially toxic levels of 7-DHC levels are also underway, and statins, the class of drugs taken by adults to reduce their cholesterol levels, have shown some promising results. It may seem counter-intuitive to administer a cholesterol reducing agent, but it is postulated that statins will stop the already flawed synthetic process of cholesterol at an earlier stage and prevent the accumulation of 7-DHC. There are a number of surgical procedures that could be recommended to repair structural malformations. These may include removal of extra digits, heart surgery, cleft palate repair and the placement of an artificial feeding device to ensure proper intake of nutrients. Hearing aids may help those with hearing problems and patients are also encouraged to avoid sun exposure because their skin is more easily damaged than that of a typical healthy person. Physical therapy can help to increase muscle strength and coordination, and there are many developmental centers that can help parents learn how to deal with the behavioral problems that may arise.


Lifespan can be limited by serious internal malformations, but with good nutrition and medical care, a normal lifespan is possible for those with a more mild form of the disease. Hopefully long-term survival rates and fewer complications will become more common as a result of cholesterol supplementation, statin use and hormone replacement therapy.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


Gene Reviews
Great resource for the genetic background of SLOS as well as associated symptoms and methods of prenatal diagnosis.

Information about the role of cholesterol, the status of current research and diagnostic procedures.

The Arc of the United States
A national organization devoted to the advancement of the mentally handicapped with information about federal and state resources and much more.

Disorder Zone Archives
Personal stories of other affected families and some good links.

Family Village
Good starting point for useful general information.

NIH Genetics Website
A lot of excellent medical information and links to helpful resources.

Google Search for Smith Lemli Opitz Syndrome (SLOS)

References and Sources

eMedicine Gene Reviews