Smith-Lemli-Opitz syndrome

Rare Nephrology News

5683

Rare Nephrology News

Disease Profile

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

Q87.1

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.

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

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

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:

Genetics specialist
Gastroenterologist
Neurologist
Cardiologist
Dietitian or nutritionist

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.

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: https://www.smithlemliopitz.org

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

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.

Rare Nephrology News

Rare Nephrology
& Urology News

Rare Nephrology
& Urology News

Infancy

Q87.1

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Treatment

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology & Urology News

Rare Nephrology & Urology News

Infancy

Q87.1

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology
& Urology News

Rare Nephrology
& Urology News

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.

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