Smith-Lemli-Opitz syndrome

Title

Other Names:

Smith Lemli Opitz syndrome; SLO syndrome; 7-Dehydrocholesterol reductase deficiency; Smith Lemli Opitz syndrome; SLO syndrome; 7-Dehydrocholesterol reductase deficiency; RSH syndrome; SLOS; Rutledge lethal multiple congenital anomaly syndrome; Polydactyly, sex reversal, renal hypoplasia, and unilobular lung; Lethal acrodysgenital syndrome See More

Categories:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases; Eye diseases; Kidney and Urinary Diseases; Metabolic disorders; Mouth Diseases; Musculoskeletal Diseases; Nervous System Diseases; RDCRN See More

Summary 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]

Last updated: 5/6/2020

Symptoms 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]

Last updated: 5/6/2020

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.

Showing of 153 |

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	More than typical sleepiness during day	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
Wide intermamillary distance	Wide-spaced nipples Widely spaced nipples Widely-spaced nipples [ more ]	0006610
Wide mouth	Broad mouth Large mouth [ more ]	0000154
5%-29% of people have these symptoms
Abnormal eyelash morphology	Abnormal eyelashes Abnormality of the eyelashes Eyelash abnormality [ more ]	0000499
Abnormal form of the vertebral bodies		0003312
Abnormal localization of kidney	Abnormal localisation of kidneys	0100542
Abnormality of dental enamel	Abnormal tooth enamel Enamel abnormalities Enamel abnormality [ more ]	0000682
Abnormality of the gallbladder		0005264
Abnormality of the ribs	Rib abnormalities	0000772
Advanced eruption of teeth	Early eruption of teeth	0006288
Aganglionic megacolon	Enlarged colon lacking nerve cells	0002251
Aplasia/Hypoplasia affecting the eye	Absent/small eye Absent/underdeveloped eye [ more ]	0008056
Aplasia/Hypoplasia of the corpus callosum		0007370
Aplasia/Hypoplasia of the radius		0006501
Bifid tongue	Cleft tongue Forked tongue Split tongue [ more ]	0010297
Brachydactyly	Short fingers or toes	0001156
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Choanal atresia	Blockage of the rear opening of the nasal cavity Obstruction of the rear opening of the nasal cavity [ more ]	0000453
Congenital diaphragmatic hernia		0000776
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Finger syndactyly		0006101
Gastroschisis		0001543
Glaucoma		0000501
Holoprosencephaly		0001360
Hydronephrosis		0000126
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypertonia		0001276
Hypopigmentation of hair	Loss of hair color	0005599
Increased number of teeth	Extra teeth Increased tooth count Supplemental teeth [ more ]	0011069
Iris coloboma	Cat eye	0000612
Kyphosis	Hunched back Round back [ more ]	0002808
Mesomelia	Disproportionately short middle portion of limb	0003027
Microglossia	Abnormally small tongue Underdevelopment of the tongue [ more ]	0000171
Multicystic kidney dysplasia		0000003
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Optic atrophy		0000648
Patent ductus arteriosus		0001643
Proptosis	Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ]	0000520
Pyloric stenosis		0002021
Reduced number of teeth	Decreased tooth count	0009804
Renal hypoplasia/aplasia	Absent/small kidney Absent/underdeveloped kidney [ more ]	0008678
Rhizomelia	Disproportionately short upper portion of limb	0008905
Sclerocornea	Hardening of skin and connective tissue	0000647
Scoliosis		0002650
Seizure		0001250
Sensorineural hearing impairment		0000407
Split hand	Claw hand Claw hand deformities Claw hands Claw-hand deformities Split-hand [ more ]	0001171
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Talipes calcaneovalgus		0001884
Ulnar deviation of finger	Finger bends toward pinky	0009465
Upslanted palpebral fissure	Upward slanting of the opening between the eyelids	0000582
Ureteropelvic junction obstruction		0000074
Percent of people who have these symptoms is not available through HPO
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Autosomal recessive inheritance		0000007
Bicornuate uterus	Heart shaped uterus Heart-shaped uterus [ more ]	0000813
Bifid scrotum	Cleft of scrotum	0000048
Breech presentation	Feet or buttocks of fetus positioned near opening of uterus	0001623
Broad alveolar ridges		0000187
Cholestatic liver disease		0002611
Coarctation of aorta	Narrowing of aorta Narrowing of the aorta [ more ]	0001680
Constipation		0002019
Dandy-Walker malformation		0001305
Decreased fetal movement	Less than 10 fetal movements in 12 hours	0001558
Dental crowding	Crowded teeth Dental overcrowding Overcrowding of teeth [ more ]	0000678
Eczema		0000964
Epiphyseal stippling	Speckled calcifications in end part of bone	0010655
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Gastrointestinal dysmotility		0002579
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hammertoe	Hammer toe Hammertoes [ more ]	0001765
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Hip subluxation	Partial hip dislocation	0030043
Hydrocephalus	Too much cerebrospinal fluid in the brain	0000238
Hyperactivity	More active than typical	0000752
Hypocholesterolemia	Decreased circulating cholesterol level	0003146
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Hypoplasia of the frontal lobes	Underdeveloped frontal lobe	0007333
Intestinal malrotation		0002566
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Metatarsus adductus	Front half of foot turns inward	0001840
Micromelia	Smaller or shorter than typical limbs	0002983
Micropenis	Short penis Small penis [ more ]	0000054
Narrow forehead	Decreased width of the forehead	0000341
Overlapping toe	Overlapping toes Overriding toes [ more ]	0001845
Periventricular heterotopia		0007165
Poor suck	Poor sucking	0002033
Posteriorly rotated ears	Ears rotated toward back of head	0000358
Precocious puberty	Early onset of puberty Early puberty [ more ]	0000826
Premature birth	Premature delivery of affected infants Preterm delivery [ more ]	0001622
Recurrent otitis media	Recurrent middle ear infection	0000403
Renal agenesis	Absent kidney Missing kidney [ more ]	0000104
Renal cyst	Kidney cyst	0000107
Renal hypoplasia	Small kidneys Underdeveloped kidneys [ more ]	0000089
Scrotal hypoplasia	Smaller than typical growth of scrotum	0000046
Self-mutilation	Deliberate self-harm Self mutilation [ more ]	0000742
Septate vagina	Double vagina	0001153
Severe photosensitivity	Severe sun sensitivity	0007537
Short stature	Decreased body height Small stature [ more ]	0004322
Short thumb	Short thumbs Small thumbs [ more ]	0009778
Short toe	Short toes Stubby toes [ more ]	0001831
Sleep-wake cycle disturbance		0006979
Unilateral renal agenesis	Absent kidney on one side Missing one kidney Single kidney [ more ]	0000122
Vomiting	Throwing up	0002013

Showing of 153 |

Last updated: 7/1/2020

Cause Cause

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

Last updated: 5/6/2020

Inheritance Inheritance

Smith-Lemli-Opitz syndrome is inherited in an autosomal recessive pattern.^[1]^[3] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be changed to have the condition.

People with autosomal recessive conditions inherit one changed gene from each of their parents. The parents are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 5/6/2020

Diagnosis 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]

Last updated: 5/6/2020

Treatment 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:

Genetics specialist
Gastroenterologist
Neurologist
Cardiologist
Dietitian or nutritionist

Last updated: 5/6/2020

Statistics Statistics

Smith-Lemli-Opitz syndrome affects an estimated 1 in 40,000 to 1 in 70,000 newborns in North America.^[3] The exact incidence of this condition is unknown.

Last updated: 5/6/2020

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
he differential diagnosis includes lathosterolosis, desmosterolosis, Dubowitz syndrome, Cornelia De Lange syndrome, oculo-digito-esophago-duodenal syndrome, Noonan syndrome, Pallister-Hall syndrome, trisomy 13 and trisomy 18 (see these terms), and pseudotrisomy 13. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Action Medical Research is a British medical research charity that funds research into rare diseases affecting children. This group has funded over £100 million in research projects. Click on the link to access information about their research into Smith-Lemli-Opitz syndrome.
ClinicalTrials.gov lists trials that are related to Smith-Lemli-Opitz syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The Sterol and Isoprenoid Diseases Consortium (STAIR) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Steroid and Isoprenoid Research Consortium (STAIR) has a registry for patients who wish to be contacted about clinical research opportunities.

For more information on the registry see: !LINK!

Organizations 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

Smith-Lemli-Opitz/RSH Foundation
PO Box 10598
Fargo, ND 58106-0598
Telephone: 701-367-1976 or 701-566-7003
E-mail: gnoah@smithlemliopitz.org
Website: http://www.smithlemliopitz.org

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More 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.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

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References References

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.
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.
Nowaczyk MJM, Wassif CA. Smith-Lemli-Opitz syndrome. GeneReviews. Updated Jan 30, 2020; https://www.ncbi.nlm.nih.gov/books/NBK1143/.
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.
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.
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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