Smith-Lemli-Opitz syndrome

This is part of Rare diseases.

Diagnosis: Smith-Lemli-Opitz syndrome

Synonyms: SLOS, SLO syndrome


Date of publication: 2009-12-16
Version: 2.1

The disease

Smith-Lemli-Opitz syndrome (SLOS) is a congenital, inherited disorder affecting the metabolism and characterised by delayed development, congenital malformations and impaired mobility.

The syndrome was described for the first time in 1964 and is named after American paediatrician, David Weyhe Smith, Belgian paediatrician Luc Lemli and American geneticist John Marius Opitz.


It is not known how common the syndrome is. Despite the identification of the gene and the possibility of making a definite diagnosis, the incidence is still not known. In a previous US study the incidence was estimated at between two and five cases per 100,000 newborns. Extrapolating to Sweden, this means that between two and five children may be born annually with the disease. Variations between rates of occurrence in different population groups can be considerable, as can the degree of disability, which means it may be difficult to identify all those with the syndrome.

Although the estimated number of carriers of the abnormal or mutated gene which causes the syndrome is relatively high, there is no direct correlation with the number of confirmed cases. There are presumably several reasons for this. Those who are most seriously affected do not survive the prenatal or postnatal stages. In the mildest forms it can be difficult to identify the syndrome and the diagnosis may therefore not be confirmed. There are presumably other genetic factors which affect the way the syndrome presents, as there are children with identical genetic mutations, but who have widely differing degrees of disability.


The source of the syndrome is an inherited deficiency in the ability to produce cholesterol. All cells in the body produce cholesterol, an important component in cell membranes, needed, among other things, for the production of bile acids, hormones and myelin, which are important for the nervous system. An inability to produce cholesterol is caused by a deficiency in enzyme 7-dehydrocholesterol-7-reductase, which is essential in the final stage of the chemical process which results in cholesterol. With reduced levels of the enzyme, the cholesterol precursors (7-dehydrocholesterol and 8-dehydrocholesterol) accumulate. These precursors can only partially replace cholesterol and are presumably toxic, although to what extent is not established.

The gene which controls the creation of (encodes for) enzyme 7-dehydrocholesterol-7-reductase was localised to chromosome 11 in 1998, and is known as DHCR7. Since then more than 130 mutations have been found which result in this enzyme deficiency. It is estimated that the most common form of the mutation is found in about one third of all those with the syndrome in Western Europe. Among people with the disease there is variation in the degree of enzyme deficiency. Generally, the more of the active enzyme is present, the milder the disease. Still, there can be variations in the symptoms displayed by different children who have the same degree of enzyme deficiency as well as the same genetic mutation.


The inheritance pattern of Smith-Lemli-Opitz syndrome is autosomal recessive. This means that two copies of the mutated gene are needed in order to develop the disease. If both parents have only one copy of the mutated gene they are called healthy carriers. Their children will have a 25 per cent risk of inheriting two mutated genes (one from each parent) and developing the disease. In 50 per cent of the cases the child will inherit only one copy of the mutated gene and become a healthy carrier. In 25 per cent of the cases the child will inherit two normal genes and will neither develop the disease nor pass it down.

Figure. Autosomal recessive inheritance of genetic traits


There are great variations in the type and severity of the symptoms displayed by different children. The most familiar picture is of those children with the greatest disabilities. In severe cases it is very common that they have problems sucking and swallowing. Children often vomit many times a day during the first years of life, which makes feeding very complicated. Consequently, children with the syndrome have difficulty in gaining weight and growing. There are also often problems with both constipation and diarrhoea. Growth retardation is also part of the syndrome. Hormonal abnormalities may also impair growth and the course of puberty. Children with the syndrome often have sleeping problems and may have long periods of wakefulness during the night.

Many children suffer severe motor impairment caused by loss of central (brain and spinal cord) and peripheral (other parts of the body) nerve functions. Hearing and vision deficits are common. Vision impairment can be caused by opaque lenses (cataracts), refractive disorders and/or damage to the optic nerve. It is common that children with the syndrome have moderate to severe mental disabilities and do not develop speech.

Most children have a particular sensitivity to UV radiation and react negatively to sunshine, even when filtered through a window. Although there is no evidence of any specific immunodeficiency, these children are prone to recurrent ear infections, and infections in the upper and lower respiratory tracts (often in the form of pneumonia.)

The syndrome is associated with a characteristic appearance, including a small head (microcephaly), a small chin (micrognathia) and a broad, upturned nose. Some children have cleft palates. A simian crease (on the palm of the hand), extra toes or fingers or webbing of the second and third toes may also present. Boys with the syndrome often have genital malformations. One example is hypospadia, when the urethra opens on the underside of the penis.

Some children have congenital heart defects. Other malformations in the brain, urethra and intestines may also occur. Moderately elevated concentrations of liver enzymes may be detected in some people with the syndrome. Acute liver disease, unresponsive to treatment, may present in severely affected neonates. Liver disease may also present in adolescence where its severity varies.

For some, the disorder progresses slowly, with increasing muscle weakness, deformities, and susceptibility to infections, general deterioration in health, and premature death. In others the condition is more stable and people with the disease survive into adulthood.


The diagnosis is established in a special laboratory by measuring blood concentrations of cholesterol and 7- and 8-dehydrocholesterol. In Smith-Lemli-Opitz syndrome the cholesterol concentration is low and the level of dehydrocholesterols is elevated. The cholesterol analysis in a regular blood lipid examination will not detect abnormalities characteristic of Smith-Lemli-Opitz syndrome.

Pre-natal and DNA-based diagnoses are possible.


There is currently no cure for Smith-Lemli-Opitz syndrome. Efforts are aimed at symptom relief and at compensation for functional disabilities.

Dietary treatment involving cholesterol supplements may alleviate symptoms such as light sensitivity. In some cases bile acid supplements are given. Intellectual ability is not affected by diet, as the brain produces its own cholesterol. All children with Smith-Lemli-Opitz syndrome should be offered dietary treatment although it is not clear who will benefit most from cholesterol treatment or how long it should continue.

Trials have been carried out with drugs (statins) to inhibit the synthesis of cholesterol, in order to affect cholesterol production. Statins may be of therapeutic value for mildly affected patients with minor enzyme, and moderate cholesterol, deficiencies. In more severe cases, however, there is a risk that statins will further lower cholesterol levels in the cells. International research projects are under way to clarify the role of statins in future treatment.

When critical situations arise, such as severe infections, surgery or injury, it can be vital for those people with Smith-Lemli-Opitz syndrome to be given cortisone.

Feeding children with this condition is time consuming. In order for them to receive sufficient nourishment a direct connection may be made between the abdominal wall and the stomach, a percutaneous endoscopic gastrostomy (PEG).

Others need to be tube fed, often with the help of a feeding pump, for many years. Feeding problems tend to be most severe for the first few years of life, and more than half of the children with the syndrome need to be fed by PEG or tube for several years. Laxatives may be necessary on occasions. Regular contact with a dietician who can assess nutritional needs is essential. As feeding problems and frequent vomiting increase the risk of dental cavities (caries), it is important that the child receives frequent dental check ups and preventive treatment.

During the early stages of life an examination should be carried out to determine possible congenital heart problems. The type of problem and the degree of severity determine treatment. Some heart defects require surgery.

Certain genital deformities are treated with hormones.

As the children are sun-sensitive they should use sunscreen with a high sun protection factor in the spring and summer, even in the shade. Soothing skin medication may also be required on occasion.

Eye examinations should be carried out at an early stage, as cataracts or drooping eyelids may require surgical treatment. Checkups should then be performed regularly as it has been observed that cataracts can develop relatively quickly. Increased eye irritation may occur. Many people require spectacles, but not all forms of poor vision can be alleviated in this way. It is also important to assess hearing at an early stage as some children have hearing difficulties.

The child requires early habilitation measures as well as auditory and visual training. Habilitation teams include professionals who have special expertise in disabilities and their effect on everyday life, health and development. Medical, educational, psychological and social support and treatment are offered. Help includes assessment, treatment, assistance with aids, information on the specific disability, and counselling. It also includes all possible community support and advice on adjustments to the home environment and other places where the child spends time. Parents and siblings should also be offered specific support to help them cope with everyday life.

Support should be based on the needs of the child. This will vary over time and be planned in close collaboration with those adults in the child’s immediate environment. Children with Smith-Lemli-Opitz syndrome require special education. The Swedish Network for Smith-Lemli-Opitz syndrome has published an information folder including advice and hints about games, exercises and stimulating activities (see under “Information material”). As few children with the syndrome learn to talk, it is essential to work with “augmentative and alternative communication” (AAC). Most of the children with the syndrome can make themselves understood using body language, sounds, signs or pictures. Some children may need technical support in the form of visual and auditory aids.

The local authority can offer different forms of help to make the daily life of the family easier. Relief can take the form of the provision of personal assistance or a contact family. It may also be in the form of short-term residential or respite care, designed to meet the needs of the individual family. This is extremely important as nearly all children with the syndrome have problems sleeping, with long periods of wakefulness during the nights. The family may also need help with coordinating various interventions.

Adults with the syndrome need continued medical and habilitation provision.

Practical advice

Valuable practical advice (in Swedish only) is available in an information folder on the syndrome that can be ordered from FUB. (See under “Information material.”)

National and regional resources in Sweden

Laboratory diagnosis is carried out at:

The Center for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Tel +46 8 585 800 00.

Also at The Neurochemical Laboratory, Sahlgrenska University Hospital/Mölndal, SE-431 80 Mölndal, Sweden. Tel +46 31 343 10 00.

The Sachs’ Children’s Hospital Knowledge Centre for Smith-Lemli-Opitz syndrome was established in Stockholm in 1996. The mission of the centre is to spread information and improve the care of children with the syndrome. The centre has developed a medical care programme for the syndrome. Contact paediatric neurologist Lena Starck (see under “Resource personnel”).

Resource personnel

Professor Ingemar Björkhem, The Centre for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Tel +46 8 585 800 00.

Assistant Professor Ulrika von Döbeln, The Centre for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Tel +46 8 585 800 00.

Lena Starck, paediatric neurologist, Sachs’ Children’s Hospital, SE-118 83 Stockholm, Sweden. Tel +46 8 616 40 00.

Courses, exchanges of experience, recreation


Organizations for the disabled/patient associations

The JMR Foundation, an organization for people with Smith-Lemli-Opitz syndrome, was founded in 2009 to spread information about the syndrome (in Swedish only). See: http://stiftelse.jmr.se/, email: post info@jmr.se.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities. Industrivägen 7 (visitors address), Box 1181, 171 23 Solna, Sweden. Tel +46 8 508 866 00, fax +46 8 508 866 66, email: fub@fub.se, www.fub.se.

There are both British and American associations, the American one having a worldwide membership. 

Courses, exchanges of experience for personnel


Research and development (R&D)


Information material

An information leaflet on Smith-Lemli-Opitz syndrome that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 1996-126-1009). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

The Knowledge Centre for Smith-Lemli-Opitz syndrome has produced a leaflet about the syndrome and an information folder about treatment (in Swedish). The folder includes accounts from parents and advice on communication, stimulating activities, toys, feeding, motor skills training, aids, support and respite care. This material can be ordered from FUB. Find the address under the heading, Organizations for the disabled/patient associations.”

An association for people with Smith-Lemli-Opitz syndrome, with the aim of spreading knowledge about the syndrome, was set up in 2009. For further information see http://stiftelse.jmr.se/.


“Severe limitations, many possibilities” is a film about what is possible despite severe disabilities. One of the three young people who contributed to the film has Smith-Lemli-Opitz syndrome. The film can be ordered from FUB. Find the address under the heading “Organizations for the disabled/patient associations.”


Nowaczyk MJ, Waye JS, Douketis JD. DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients? Am J Med Genet A 2006; 140: 2057-2062.

Opitz JM. RSH/SLO (“Smith-Lemli-Opitz”) syndrome: historical, genetic, and developmental considerations. Am J Med Genet 1994; 50: 344-346.

Porter FD. Smith-Lemli-Opitz syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet 2008; 16: 535-541.

Starck L, Björkhem I, Lund E, von Döbeln U. Nya möjligheter för barn med Smith-Lemli-Opitz syndrom. Defekt upptäckt i kolesterolsyntesen. Läkartidningen 1995; 92: 3325-3329.

Starck L, Lövgren-Sandblom A, Björkhem I. Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome. J Intern Med 2002; 252: 314-321.

Starck L, Lövgren-Sandblom A, Björkhem I. Simvastin treatment in the SLO syndrome - A safe approach? Am J Med Genet 2002; 113: 183-189.

Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994; 330: 107-113.

Tint GS, Abuelo D, Till M, Cordier MP, Batta AK, Shefer S et al. Fetal Smith-Lemli-Opitz syndrome can be detected accurately and reliably by measuring amniotic fluid dehydrocholesterols. Prenat Diagn 1998; 18: 651-658.

Database references

OMIM (Online Mendelian Inheritance in Man).
Internet: http://www.ncbi.nlm.nih.gov/omim/
Key word: Smith-Lemli-Opitz syndrome

GeneReviews (University of Washington)
Internet: www.genetests.org (select GeneReviews)
Key word: Smith-Lemli-Opitz syndrome

Document Information

The Swedish Information Centre for Rare Diseases produced and edited this material.

The medical expert who wrote the draft is Lena Starck, paediatric neurologist, Sachs Children’s Hospital, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

The expert group on rare diseases of the Swedish National Board of Health and Welfare approved the material prior to publication.

Date of publication: 2009-12-16
Version: 2.1
Publication date of the Swedish version: 2009-05-25

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden, tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.