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Kearns-Sayre syndrome
Kearns-Sayre syndrome is a rare genetic condition impacting energy production in cells, leading to progressive muscle weakness around the eyes, vision changes, and heart problems. It can affect children and young adults, often requiring lifelong medical management.
Overview
Kearns-Sayre syndrome (KSS) is a rare, slowly progressive mitochondrial condition. Mitochondria are often called the 'powerhouses' of our cells because they generate most of the energy needed for cellular function. In KSS, the mitochondria do not work as they should, particularly in tissues with high energy demands like muscles, eyes, and the heart [PMID:33678516]. This leads to a range of symptoms that typically begin before the age of 20 years. KSS can vary significantly in its presentation and severity among affected individuals. The condition is sometimes considered part of a spectrum of mitochondrial disorders.
Symptoms & clinical features
The main symptoms of Kearns-Sayre syndrome include progressive external ophthalmoplegia, which is a gradual weakness or paralysis of the muscles that move the eyes, leading to difficulty moving them or keeping them open [PMID:33678516]. Another key feature is pigmentary retinopathy, a type of retinal degeneration that affects vision, especially in low light conditions. Individuals with KSS also often develop cardiac conduction defects, which are abnormalities in the electrical signals that control the heartbeat. These can be serious and may require a pacemaker [PMID:33678516].
Other symptoms can include weakness of other skeletal muscles, deafness, short stature, and neurological issues such as ataxia (problems with coordination and balance). Hormonal problems, such as diabetes or thyroid dysfunction, may also occur. Kidney problems can also be part of the syndrome, affecting how well the kidneys filter waste from the blood. The combination and severity of these symptoms can differ greatly from person to person.
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Affected organs
Kearns-Sayre syndrome primarily affects organs and tissues with high energy demands. The eyes are significantly impacted, leading to problems with eye movement muscles and the retina. The heart is also critically affected, particularly its electrical conduction system. Skeletal muscles throughout the body can show weakness, and the brain may be involved, leading to neurological symptoms. Other organs that can be affected include the ears (hearing loss), endocrine glands (hormonal imbalances), and kidneys.
Risks & severity
Kearns-Sayre syndrome is a progressive condition, meaning symptoms tend to worsen over time. The age of onset is typically before 20 years. The severity of KSS varies considerably; some individuals experience milder symptoms, while others face significant health challenges. Cardiac involvement, specifically heart block, is a major concern and can be life-threatening if not managed appropriately. The development of other features, such as diabetes or kidney disease, also influences the overall severity and management strategy. Regular monitoring is essential to detect and address potential complications early.
Genetic causes
Kearns-Sayre syndrome is generally caused by large deletions in mitochondrial DNA (mtDNA) [PMID:24759981]. Mitochondria contain their own small circular DNA, separate from the DNA found in the cell's nucleus. This mtDNA contains genes essential for producing energy within the cell. In KSS, a segment of this mitochondrial DNA is missing, which disrupts the normal functioning of the energy production pathways. These deletions typically occur spontaneously and are not usually inherited from parents in the classic sense.
While mtDNA deletions are the primary cause, the exact size and location of the deletion, and the proportion of affected mitochondria within cells (known as heteroplasmy), can influence the range and severity of symptoms. Most cases of KSS are considered sporadic, meaning they occur in individuals without a family history of the condition. There are no specific nuclear genes consistently associated with KSS listed in our current reference dataset.
Inheritance pattern
Kearns-Sayre syndrome typically follows a mitochondrial inheritance pattern, though most cases are sporadic. This means that the genetic changes causing KSS arise spontaneously in the mitochondrial DNA after conception, rather than being passed down from a parent. Therefore, parents of an affected child usually have a very low risk of having another child with the condition.
Unlike nuclear DNA, which is inherited from both parents, mitochondrial DNA is almost exclusively inherited from the mother. However, because the deletions causing KSS are generally new mutations, the risk to siblings or future children of an affected individual is usually very low. Genetic counselling can provide specific information about inheritance risks based on an individual's unique situation.
Diagnosis & testing
Diagnosing Kearns-Sayre syndrome involves a combination of clinical evaluation, specialised tests, and genetic testing. The presence of the characteristic triad of progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction defects, with onset before age 20, strongly suggests KSS. Diagnostic tests may include an electrocardiogram (ECG) to check heart rhythm, an ophthalmological examination to assess eye muscles and retina, and sometimes muscle biopsies to look for specific abnormalities like 'ragged-red fibres' under a microscope.
Genetic testing is crucial for confirming the diagnosis. This typically involves looking for large deletions in mitochondrial DNA, often from blood or muscle tissue. Referral for genetic testing is usually made by a neurologist, cardiologist, or clinical geneticist. In the UK, genetic testing for mitochondrial disorders falls under the NHS Genomic Medicine Service, often utilising R-codes for specialised testing pathways, such as R86 (Mitochondrial DNA Disorders - Single Gene/Small Panel) or R88 (Mitochondrial DNA Disorders - Large Panel/Whole mtDNA).
Management & lifestyle
Management of Kearns-Sayre syndrome focuses on addressing the symptoms and preventing complications, as there is currently no cure. Care is highly individualised and typically involves a multidisciplinary team of specialists, including neurologists, cardiologists, ophthalmologists, and endocrinologists. Regular monitoring of heart function, including ECGs and potentially a Holter monitor, is essential, and a pacemaker may be implanted to manage heart block.
Vision and hearing should be regularly assessed, and aids can be provided as needed. Physical therapy may help with muscle weakness, and occupational therapy can assist with daily activities. Hormonal imbalances, such as diabetes or thyroid dysfunction, are managed with appropriate medication. Genetic counsellors play a vital role in providing information and support to individuals and families. Patients in the UK would typically access care through their local NHS Trust, often involving specialist mitochondrial disease centres.
UK care pathway
In the UK, individuals suspected of having Kearns-Sayre syndrome would typically be referred by their GP or a specialist to a clinical geneticist or a specialist mitochondrial disease centre within the NHS. These centres offer comprehensive diagnostic services and ongoing management. Genetic testing is provided through the NHS Genomic Medicine Service, following specific R-codes for mitochondrial disorders. Genetic counsellors are available to explain the condition, inheritance patterns, and support families through the diagnostic and management journey.
Frequently asked questions
Is Kearns-Sayre syndrome always inherited from my parents?
No, Kearns-Sayre syndrome is typically not inherited from parents in the traditional sense. It usually results from a new, spontaneous genetic change in the mitochondrial DNA that occurs during or after conception. This means that in most cases, parents of an affected child do not carry the deletion themselves.
How serious are the heart problems in Kearns-Sayre syndrome?
Heart problems, particularly issues with the heart's electrical conduction system (heart block), can be very serious in Kearns-Sayre syndrome. They are a major cause for concern and often require close monitoring and sometimes the implantation of a pacemaker to regulate the heartbeat.
Can my vision and eye movement improve with treatment?
While there is no cure for the underlying cause of Kearns-Sayre syndrome, treatments focus on managing symptoms. Unfortunately, the progressive weakness of eye muscles and the retinal degeneration typically do not improve. However, vision aids and supportive therapies can help manage the impact on daily life.
What kind of doctors will I see if I have Kearns-Sayre syndrome?
You will likely be seen by a team of different specialists. This often includes neurologists for muscle and brain issues, cardiologists for heart problems, ophthalmologists for eye care, endocrinologists for hormone imbalances, and geneticists or genetic counsellors for overall coordination and support.
Is Kearns-Sayre syndrome a common condition?
No, Kearns-Sayre syndrome is considered a rare condition. Its exact prevalence is not well established, but it affects a very small number of people worldwide.
References
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- Shemesh A, Margolin E. Kearns-Sayre Syndrome. 2023. PMID: 29493966
- Zeviani M, Carelli V. Mitochondrial Retinopathies. International journal of molecular sciences. 2021. PMID: 35008635
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- Petropoulou A, Kypraios N, Rizopoulou D. Mitochondrial tRNA-Derived Diseases. International journal of molecular sciences. 2025. PMID: 41465450