NORD gratefully acknowledges Emily Furno, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Smith-Lemli-Opitz syndrome (SLOS) is a genetic condition that affects many parts of the body. It is an autosomal recessive genetic condition caused by changes in the DHCR7 gene. Problems associated with SLOS are usually noticeable before or shortly after birth (congenital). Common features of SLOS include slow growth, a small head (microcephaly) and mild to severe intellectual disability. Birth defects such as extra fingers and toes (polydactyly) are also common. SLOS is a variable condition. Some individuals with SLOS have normal development and only minor features. SLOS affects 1 in 20,000 to 1 in 60,000 babies born in the United States. People with SLOS cannot make cholesterol. Treatment with extra cholesterol may help with some signs of SLOS, however, no cure for SLOS currently exists.
The features of SLOS are not the same in every patient. Common findings are slowed growth before and after birth, a small head (microcephaly) and a spilt in the roof of the mouth (cleft palate). Most babies have differences in their fingers and/or toes. This includes fused toes (2-3 syndactyly) and extra fingers or toes (polydactyly). Males with SLOS can have underdeveloped genitals that may resemble female genitals. People with SLOS often experience behavioral problems, sleep problems and mild to severe intellectual disability.
Individuals with SLOS have specific facial features. Their eyes may appear to be drooping (ptosis). There can also be a fold in the inner corner of the eye (epicanthal folds) and wrinkles on the eyelids. Children with SLOS can have a small nose and nostril differences (anteverted nares). Other common facial features include differences of the upper lip, a small jaw and large ears. Vision problems can occur, including cataracts. There may also be differences in the number and/or spacing of teeth.
Less common findings include seizures, heart defects and low muscle tone (hypotonia). People with SLOS can have a narrowing at the top of the stomach (pyloric stenosis) and blockage (obstruction) of the bowel. A sensitivity to light (photosensitivity) is also common.
The chromosomes in our cells carry our genes which occur in pairs and are instructions to make proteins. One copy of each gene is inherited from the mother, and the other from the father. SLOS is caused by having a harmful change (mutation) in both copies of the DHCR7 gene. This causes lack of an enzyme (7-dehydrocholesterol reductase) which is needed to make cholesterol. Cholesterol is a waxy substance that is important for making cell structures. Cholesterol is necessary for development before and after birth. Mistakes in DHCR7 also leads to a buildup of 7-dehydrocholesterol (7-DHC) which is toxic to the body. Buildup of 7-DHC along with low cholesterol cause the features of SLOS.
SLOS is an autosomal recessive genetic condition. Recessive genetic conditions occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass on the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same harmful gene change, which increases the risk to have children with a recessive genetic condition.
About 1 in 20,000 to 1 in 60,000 people in the US have SLOS. This condition affects males and females equally. However, females are less likely to be diagnosed because they do not have genital differences. SLOS occurs more often in people of European ancestry.
The diagnosis of SLOS is based on physical findings and either biochemical or genetic testing. Biochemical testing looks for protein levels in the blood. In patients with SLOS, the protein 7-dehydrocholesterol is elevated. Genetic testing looks for changes in a patient’s genes. SLOS is diagnosed if there are harmful changes in both copies of the DHCR7 gene.
Results from a test offered during pregnancy (maternal serum screen) may suggest SLOS. An amniocentesis can be performed to confirm the diagnosis. An amniocentesis uses a needle to take a small amount of fluid surrounding the baby during pregnancy. This fluid can be tested for 7-DHC levels or changes in the DHCR7 gene.
Treatment for SLOS is based on the child’s specific problems. Some children may require surgery to correct cleft palate, heart defects and genital anomalies. Early educational intervention is important for learning and developmental disabilities. Food with extra cholesterol and bile acid supplements may improve some of the symptoms of SLOS including growth. Statins, such as Simvastatin, can safely reduce DHC levels and may improve some behavioral problems.
Research into new therapies for SLOS is ongoing. Current clinical trials are investigating cholic acid, antioxidants, cholesterol and other dietary supplements. There is also some evidence that early liver transplantation may be considered in people with SLOS.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
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Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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