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Last updated: 3/18/2025
Years published: 1987, 1996, 1999, 2000, 2001, 2007, 2010, 2013, 2016, 2020, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, Amy Goldstein, MD, Clinical Director, Mitochondrial Medicine Frontier Program, Children’s Hospital of Philadelphia; Associate Professor of Clinical Pediatrics, University of Pennsylvania Perelman School of Medicine, and Patrick Lestienne, Directeur de Recherches a l’Institut National de la Sante et de la Recherche Medicale (INSERM), France, for assistance in the preparation of this report.
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Kearns-Sayre syndrome (KSS) is a rare disorder that affects many organs and systems of the body. This disease is mostly characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa) or pigmentary retinopathy, leading to poor night vision and progressive vision loss; and heart disease such as an enlarged heart muscle (cardiomyopathy) and/or progressive arrhythmia leading to complete heart block. Other findings may include muscle weakness, short stature, sensorineural hearing loss, endocrine issues such as diabetes mellitus and hypoparathyroidism (which can cause hypocalcemia) and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). An important feature is the presence of droopy eyelids (ptosis) in one or both eyes. In some people, KSS may be associated with other disorders and/or conditions.
KSS belongs (in part) to a group of rare disorders known as mitochondrial encephalomyopathies. In these disorders there is a change (variant) in a gene in the mitochondria, the cell structure that produces energy (in the form of adenosine triphosphate, or ATP). A lack of energy results in the brain and muscles not functioning properly and this is called an encephalomyopathy. People with these disorders have an abnormally high number of mitochondria with a gene variant. In about 80% of people with KSS, genetic testing shows missing (deleted) mitochondrial DNA (mtDNA).
Signs and symptoms of Kearns Sayre syndrome are usually apparent before the age of 20 years. The three primary findings in KSS are:
Signs and symptoms of KSS may include:
Eventually, the muscle weakness that affects the eye muscles may extend to other portions of the body and result in the following symptoms:
The normal heart has four chambers. The two upper chambers known as atria are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers known as ventricles are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles.
In some people, heart block may lead to dizziness, blackouts (syncope), breathlessness and/or irregular heartbeats (arrhythmias). Bundle-branch block may be seen on electrocardiogram (EKG) and indicates that the arrhythmia is present; this may progress unpredictable and quickly to complete heart block.
Additional signs and symptoms may include:
The relationship between KSS and endocrine abnormalities is not fully understood.
KSS may also be associated with other disorders or conditions including absence of certain reflexes (peripheral neuropathy) and progressive kidney (renal) abnormalities including chronic renal failure. Peripheral neuropathy is a disorder that may affect one or several nerves of the body causing pain and weakness. Peripheral neuropathy may affect sensory, motor, reflex, or blood vessel function.
Recent publications report damage to the spinal cord (bundle of nerves that extend from the base of the brain down the center of the spine) in some affected people.
Most cases of KKS appear to occur as the result of a new spontaneous (de novo) deletion (loss) of a large amount (typically ~25%) of mitochondrial DNA (mtDNA). Mitochondria, which are found by the hundreds in the cells of the body, particularly in muscle and nerve tissue, are structures that carry the blueprints for regulating energy production. As opposed to the genetic instructions of cellular chromosomes (nuclear DNA) which are found in the nucleus of each cell, multiple copies of mitochondrial DNA are found outside of the nucleus of the cell and within the mitochondria.
In extremely rare cases, deletions in mtDNA may be inherited from the mother. The mtDNA found in sperm cells typically break off during fertilization. As a result, it is thought that human mtDNA comes only from the mother. An affected mother may pass the mitochondrial gene variants(s) on to all her children but only her daughters will pass the variant(s) on to their children.
Both normal and altered mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of abnormal mitochondria may be outnumbered by the number of normal mitochondria. Symptoms of KSS may not appear in any given generation until the deletion affects a significant proportion of mitochondria. The uneven distribution of normal and altered mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms and different degrees of severity in affected family members. This can also mean that the mtDNA deletion might not be detected in some tissues such as blood or cheek swab but can be found in other tissues such as muscle biopsy, and this confirms the diagnosis.
KSS is a mitochondrial disorder that affects males and females in equal numbers. The prevalence of Kearns-Sayre syndrome is approximately 1 to 3 per 100,000 individuals. Onset is typically before the age of 20, but symptoms may appear during infancy or adulthood. Eye abnormalities and developmental delays are often observed before the age of five.
Some researchers think that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like KSS.
The diagnosis of KSS may be suspected when the three primary characteristics associated with this disorder occur by the age of 20 years. These include paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]), abnormal coloration of the delicate membrane lining the eyes (atypical retinitis pigmentosa) and other changes in the structures of the eye (pigmentary degeneration of the retina) and disease affecting the heart (cardiomyopathy), especially conduction disorders (e.g., heart block). Diagnosis of KSS may be confirmed by a thorough clinical evaluation and a variety of specialized tests.
The specialized tests may include an electrocardiogram to detect the presence and evaluate the severity of heart block, blood and spinal fluid lactic acid levels, a muscle biopsy to demonstrate the presence of characteristic abnormalities in muscle tissue (ragged-red fibers) and/or a spinal tap to determine whether there are elevated levels of cerebrospinal fluid (CSF) protein (>100 mg/dL) or a deficiency of folate (cerebral folate deficiency). The muscle biopsy can determine the presence of deleted mtDNA, which may not be detected in the blood sample. In some people with KSS, the levels of other substances (i.e., serum creatine kinase, blood lactate, gamma globulin and/or pyruvate) may be elevated in the blood.
Microscopic examination of biopsy tissue samples under an electron microscope may reveal large numbers of abnormal mitochondria in skeletal and eye muscle tissue. In some people, a CT scan or tomography may be used to identify abnormal accumulation of calcium in and/or lesions affecting certain areas of the brain. MRI of the brain may also show white matter changes or changes similar to Leigh syndrome.
Treatment
There is still no cure for Kearns-Sayre syndrome (KSS). Managing KSS focuses on treating symptoms and preventing complications. Since KSS affects different organs, treatment is personalized based on which systems are involved.
People with KSS are at risk for serious heart problems including complete heart block, a condition where electrical signals in the heart don’t travel properly. This can lead to a dangerously slow heart rate or even sudden cardiac arrest. To prevent this, doctors may recommend a prophylactic pacemaker, a small device placed under the skin that helps control the heartbeat. Since heart complications can be life-threatening, regular check-ups with a cardiologist (heart specialist) are essential.
People affected with KSS can also have various eye problems, including ptosis (droopy eyelids) and issues with the retina (the light-sensitive part at the back of the eye). Surgery is sometimes used to lift the eyelids and improve vision. However, whether surgery helps with retinal problems depends on how advanced the changes are. Special vision aids or assistive devices may help people with vision loss. In some people, strabismus surgery (a procedure to straighten misaligned eyes) may also be considered.
Some people with KSS develop hearing loss. When this happens, cochlear implants (small electronic devices that help restore hearing) may be an option. An audiologist (hearing specialist) can help determine the best approach.
KSS can also affect other body systems leading to conditions such as:
These conditions are usually treated with hormone replacement therapy to help balance hormone levels in the body.
Folic acid or folinic acid supplements may be recommended, especially for people with low levels of cerebral folate (a type of folate important for brain function) or neurological symptoms like difficulty thinking or moving.
Research is exploring potential new treatments for KSS such as:
Though these treatments are still being studied, some doctors may suggest Coenzyme Q10 as a supplement.
Growth hormone (GH) therapy is sometimes used to help children with KSS grow taller but its use is controversial. While some children with growth hormone deficiency have improved height with treatment, GH therapy can also be risky because it increases the body’s demand for energy (ATP, the fuel that powers cells). Since people with mitochondrial diseases already have trouble producing enough ATP, GH therapy might worsen symptoms. Some patients have developed muscle weakness, trouble with balance, memory problems and even multiple organ failure after GH therapy.
Because of these risks, doctors carefully assess whether GH treatment is appropriate for each patient. In some people, stopping GH therapy has led to improvements in muscle strength, appetite and cognitive function.
People with KSS may have weak bones (osteoporosis) which increases the risk of fractures. Doctors may consider medications such as:
However, there isn’t enough research to prove these treatments are effective in helping people with KSS.
Physical therapy, occupational therapy and social support services can improve quality of life.
Because KSS affects many parts of the body, affected people should be followed by a team of specialists including geneticists and metabolic specialists, neurologists, cardiologists, ophthalmologists, audiologists, endocrinologists, gastroenterologists and others, as needed. These specialists should work together and in a coordinated manner for the best management.
Since KSS is a genetic disorder, genetic counseling is recommended.
Support from mitochondrial disease organizations can also help patients and families connect with others facing similar challenges.
In the U.S., experts in mitochondrial diseases can be located through the Mitochondrial Care Network (www.mitonetwork.org).
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLE
Moscatelli M, Ardissone A, Lamantea E, et al. Kearns-Sayre syndrome: expanding spectrum of a “novel” mitochondrial leukomyeloencephalopathy [published correction appears in Neurol Sci. 2022 Nov;43(11):6607. doi: 10.1007/s10072-022-05950-y.]. Neurol Sci. 2022;43(3):2081-2084. doi:10.1007/s10072-022-05881-8
INTERNET
Shemesh A, Margolin E. Kearns-Sayre Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482341/ Accessed March 5, 2025.
Goldstein A, Falk MJ. Single Large-Scale Mitochondrial DNA Deletion Syndromes. 2003 Dec 17 [Updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1203/ Accessed March 5, 2025.
NINDS Kearns-Sayre Syndrome Information Page. National Institute of Neurological Disorders and Stroke (NINDS). Last reviewed on July 19, 2024.Available from: https://www.ninds.nih.gov/health-information/disorders/mitochondrial-disorders Accessed March 5, 2025.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:530000; Last Update: 06/14/2024. Available at: https://omim.org/entry/530000 Accessed March 5, 2025.
Kearns-Sayre syndrome. MedlinePlus. Last updated December 1, 2011. https://medlineplus.gov/genetics/condition/kearns-sayre-syndrome/ Accessed March 5, 2025.
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Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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