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Disease Profile

Smith-Lemli-Opitz syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Smith Lemli Opitz syndrome; SLO syndrome; 7-Dehydrocholesterol reductase deficiency;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases;

Summary

Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic condition affecting multiple body systems. Signs and symptoms may include characteristic facial features, small head size, growth and developmental delays, and intellectual and behavioral problems. Individuals with SLOS have abnormally low levels of cholesterol in their blood and high levels of a chemical known as 7-dehydrocholestrol. The severity of symptoms varies from individual to individual. Many babies have feeding difficulties and growth issues. Some are born with heart, kidney, and adrenal problems. Most people with SLOS have some degree of intellectual and behavioral difficulties. This condition is caused by genetic changes (DNA variants) in the DHCR7 gene and is inherited in an autosomal recessive pattern. This condition is diagnosed based on the features and laboratory and genetic testing. Treatment is based on the symptoms.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Smith-Lemli-Opitz syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in this condition.

Signs and symptoms of Smith-Lemli-Opitz syndrome may include:[1][2][3]

  • Microcephaly
  • Intellectual disability
  • Global developmental delay
  • Distinctive facial features
  • Feeding difficulties
  • Cleft palate
  • Underdeveloped male genitalia
  • Defect in the opening of the penis (hypospadias)
  • Extra fingers and toes (Postaxial polydactyly)
  • Webbed toes (2-3 syndactyly)
  • Heart abnormalities

Newborns with Smith-Lemli-Opitz syndrome (SLOS) are often born with characteristic facial features, extra fingers and toes, and small chin with a cleft palate. Some have heart defects, feeding issues, and gastrointestinal problems. Children with SLOS have some degree of intellectual disability and behavioral issues, such as sleep disturbances. They are often very sensitive to sunlight. Lower levels of cholesterol and increased levels of a chemical known as 7-dehydrocholesterol (7DHC) are associated with more severe features and symptoms.[1][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
2-3 toe syndactyly
Webbed 2nd and 3rd toes
0004691
Abnormal dermatoglyphics
Abnormal fingerprints
0007477
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth

[ more ]

0006482
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Elevated 7-dehydrocholesterol
0010569
Feeding difficulties in infancy
0008872
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Global developmental delay
0001263
Increased nuchal translucency
0010880
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Muscular hypotonia
Low or weak muscle tone
0001252
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal lung lobation
0002101
Abnormality of the larynx
0001600
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Atrioventricular canal defect
0006695
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Autism
0000717
Biparietal narrowing
0004422
Cleft palate
Cleft roof of mouth
0000175
Clitoral hypertrophy
Enlarged clitoris
0008665
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Cutis marmorata
0000965
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Facial capillary hemangioma
0000996
Gingival overgrowth
Gum enlargement
0000212
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias
0000047
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Long philtrum
0000343
Low-set, posteriorly rotated ears
0000368
Polyhydramnios
High levels of amniotic fluid
0001561
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

0001162
Proximal placement of thumb
Attachment of thumb close to wrist
0009623
Ptosis
Drooping upper eyelid
0000508
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

0002089
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection

[ more ]

0002719
Self-injurious behavior
Self-injurious behaviour
0100716
Short neck
Decreased length of neck
0000470
Tracheal stenosis
Narrowing of windpipe
0002777
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Ventriculomegaly
0002119

Cause

Smith-Lemli-Opitz syndrome (SLOS) is caused by genetic changes (DNA variants) in the DHCR7 gene.[4][3]

Diagnosis

Smith-Lemli-Opitz syndrome is diagnosed based on a clinical exam and a blood test to detect high levels of 7-dehydrocholesterol in the blood. Genetic testing for variants in the DHCR7 gene can confirm the diagnosis.[2][5]

Treatment

There is no specific treatment for Smith-Lemli-Opitz syndrome, and treatment is based on the symptoms. There is some evidence that adding cholesterol to the diet can be helpful, especially if started early in life.[3] Other treatments may include surgery, medications, and therapy for intellectual and developmental issues.[5]

Some of the specialists who may be involved in the care of someone with Smith-Lemli-Opitz syndrome include:

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Smith-Lemli-Opitz syndrome. This website is maintained by the National Library of Medicine.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Smith-Lemli-Opitz syndrome. Click on the link to view a sample search on this topic.

        References

        1. Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet. Nov 15, 2012; 160C(4):250-62. https://pubmed.ncbi.nlm.nih.gov/23059950.
        2. Donoghue SE, Pitt JJ, Boneh A, White SM. Smith-Lemli-Opitz syndrome: clinical and biochemical correlates. J Ped Endoc Metab. Mar 2018; 31(4):451-459. https://www.ncbi.nlm.nih.gov/pubmed/29455191.
        3. Nowaczyk MJM, Wassif CA. Smith-Lemli-Opitz syndrome. GeneReviews. Updated Jan 30, 2020; https://www.ncbi.nlm.nih.gov/books/NBK1143/.
        4. Yu H, Patel SB. Recent insights into the Smith-Lemli-Opitz syndrome. Clin Genet. Nov 2005; 68(5):383-391. https://www.ncbi.nlm.nih.gov/pubmed/16207203.
        5. Rojare C, Opdenakker Y, Labored A, Nicot R, Mention K, Ferri J. The Smith-Lemli-Opitz syndrome and dentofacial anomalies diagnostic: Case reports and review of the literature. Int J Orthod. Jun 2019; 17(2):375-383. https://www.ncbi.nlm.nih.gov/pubmed/31005410.
        6. Thurm A, Tierney E, Farmer C, Albert P, Joseph L et al. Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update. J Neurodev Disord. Apr 5, 2016; 8:12. https://pubmed.ncbi.nlm.nih.gov/27053961.

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