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Disease Profile
Leigh syndrome
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
All ages
ICD-10
G31.8
Inheritance
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.
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.
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)
LS; Subacute necrotizing encephalopathy; SNE;
Categories
Congenital and Genetic Diseases; RDCRN
Summary
Leigh
The inheritance of Leigh syndrome depends on where the responsible
- Mitochondrial DNA-associated Leigh syndrome follows a mitochondrial inheritance pattern (also called maternal inheritance).
- Nuclear gene-encoded Leigh syndrome may be inherited in an
autosomal recessive orX-linked manner.
Treatment is based on the symptoms present and depends on the type of Leigh syndrome a person has.[2][4] While life expectancy depends on the cause of Leigh syndrome in each person, most do not survive past mid-childhood or adolescence.[1]
Symptoms
Central nervous system abnormalities may include:[1][5]
- Developmental delay or regression
Nystagmus - Ophthalmoparesis (weakness in the muscles that control eye movement)
- Optic atrophy
Ataxia Dysphagia - Retinitis pigmentosa
- Deafness
Peripheral nervous system abnormalities may include polyneuropathy and myopathy.[1][5]
Although most people with Leigh syndrome only have neurological abnormalities, some people also have non-neurologic abnormalities. These may include:[5]
- Distinct physical features
Hormone abnormalities resulting inshort stature or hypertrichosis- Heart abnormalities (hypertrophic or dilated cardiomyopathy)
- Gastrointestinal symptoms such as diarrhea
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 | ||
Abnormality of movement |
Movement disorder
Unusual movement
[ more ] |
0100022 |
Ataxia | 0001251 | |
Cognitive impairment |
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] |
0100543 |
Decreased activity of mitochondrial respiratory chain | 0008972 | |
Muscular |
Low or weak muscle tone
|
0001252 |
Nystagmus |
Involuntary, rapid, rhythmic eye movements
|
0000639 |
Respiratory insufficiency |
Respiratory impairment
|
0002093 |
Cross-eyed
Squint
Squint eyes
[ more ] |
0000486 | |
30%-79% of people have these symptoms | ||
Hemiplegia/hemiparesis |
Paralysis or weakness of one side of body
|
0004374 |
Optic atrophy | 0000648 | |
Progressive ophthalmoplegia | 0007650 | |
Progressive spastic paraplegia | 0007020 | |
0001250 | ||
Percent of people who have these symptoms is not available through HPO | ||
Abnormal pattern of respiration |
Abnormal respiratory patterns
Unusual breathing patterns
[ more ] |
0002793 |
0000007 | ||
CNS demyelination | 0007305 | |
Difficulty articulating speech
|
0001260 | |
0001332 | ||
Emotional lability |
Emotional instability
|
0000712 |
Failure to thrive |
Faltering weight
Weight faltering
[ more ] |
0001508 |
Generalized hypotonia |
Decreased muscle tone
Low muscle tone
[ more ] |
0001290 |
Global |
0001263 | |
Hepatocellular necrosis |
Death of liver cells
|
0001404 |
Hyperreflexia |
Increased reflexes
|
0001347 |
Hypertrichosis | 0000998 | |
Increased CSF lactate | 0002490 | |
Increased serum lactate | 0002151 | |
Infantile onset |
Onset in first year of life
Onset in infancy
[ more ] |
0003593 |
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] |
0001249 | |
Lactic acidosis |
Increased lactate in body
|
0003128 |
0001427 | ||
Ophthalmoplegia |
Eye muscle paralysis
|
0000602 |
Pigmentary retinopathy | 0000580 | |
Progressive |
Worsens with time
|
0003676 |
Psychomotor retardation | 0025356 | |
Drooping upper eyelid
|
0000508 | |
Respiratory failure | 0002878 | |
Sensorineural hearing impairment | 0000407 | |
Involuntary muscle stiffness, contraction, or spasm
|
0001257 |
Cause
Most genes associated with Leigh syndrome are involved in the process of energy production in mitochondria (oxidative phosphorylation). Five
Diagnosis
- Progressive neurologic disease with motor and intellectual
developmental delay - Signs and symptoms of brainstem and/or basal ganglia disease
- Raised lactate concentration in blood and/or cerebrospinal fluid (CSF)
- The presence of one or more of the following:
- Characteristic features on brain
imaging (CT scan orMRI ) - Typical nervous system
tissue changes - Typical nervous system tissue changes in a similarly affected sibling
- Characteristic features on brain
After these criteria are met and a diagnosis of Leigh syndrome is made, molecular genetic testing can then differentiate between mtDNA-associated Leigh syndrome (caused by
Because not all patients have increased lactate levels, recent studies proposed new diagnostic criteria excluding the raised lactate levels as a prerequisite. The remaining criteria are similar, but add mitochondrial dysfunction as a criterion.[3]
A diagnosis of Leigh-like syndrome may be considered in individuals who do not meet the strict diagnostic criteria but have features resembling Leigh syndrome.[3]
Testing Resources
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
- Orphanet lists international laboratories offering diagnostic testing for this condition.
Treatment
Supportive care for Leigh syndrome includes treatment of acidosis,
Because anesthesia can potentially aggravate respiratory symptoms and bring on respiratory failure, careful consideration should be given to its use and close monitoring prior to, during, and after its use.[4][3]
Progression and new symptoms should be monitored regularly (typically every 6-12 months). Evaluations with a
Specific treatment is possible for the three nuclear
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
-
People Against Leigh Syndrome (PALS)
Lori Martin, Director
Houston, TX,
Telephone: 713-863-0485
E-mail: [email protected]
Website: https://peopleagainstleighs.org/
Social Networking Websites
- Visit the following Facebook groups related to Leigh syndrome:
Leigh's Syndrome Parent Network -
RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).
Organizations Providing General Support
-
Alex The Leukodystrophy Charity (Alex TLC)
45 Peckham High Street
London, SE15 5EB United Kingdom
Telephone: 020 7701 4388
E-mail: [email protected]
Website: https://www.alextlc.org -
MitoAction
PO Box 310
Novi, MI 48376
Toll-free: 888-648-6228
E-mail: [email protected]
Website: https://www.mitoaction.org/ -
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: [email protected]
Website: https://www.umdf.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
- MedlinePlus Genetics contains information on Leigh syndrome. This website is maintained by the National Library of Medicine.
- The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
- 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.
Mitochondrial DNA-Associated Leigh Syndrome
Nuclear Gene-Encoded Leigh Syndrome - 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 Leigh syndrome. Click on the link to view a sample search on this topic.
Selected Full-Text Journal Articles
- Huntsman RJ, Sinclair DB, Bhargava R, Chan A. Atypical presentations of Leigh syndrome: A case series and review. Pediatr Neurol 2005;32:334-340.
References
- Leigh's Disease Information Page. National Institute of Neurological Disorders and Stroke. December, 2011; https://www.ninds.nih.gov/disorders/leighsdisease/leighsdisease.htm.
- Leigh syndrome. Genetics Home Reference. June, 2016; https://ghr.nlm.nih.gov/condition/leigh-syndrome.
- Thronburn DR & Rahman S.. Mitochondrial DNA-Associated Leigh Syndrome and NARP. GeneReviews. April 17, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1173/.
- Rahman S & Thorburn D. Nuclear Gene-Encoded Leigh Syndrome Overview. GeneReviews. October 1, 2015; https://www.ncbi.nlm.nih.gov/books/NBK320989/.
- Finsterer J. Leigh and Leigh-Like Syndrome in Children and Adults. Pediatr Neurol. 2008; https://www.ncbi.nlm.nih.gov/pubmed/18805359.
- Leigh Syndrome. NORD. 2016; https://rarediseases.org/rare-diseases/leigh-syndrome/.
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