Kearns–Sayre Syndrome (KSS)

KSS is a rare condition, and the exact prevalence is unknown. Some sources suggest KSS affects about 1 to 3 people per 100,000.^4,5 Others suggest a slightly lower estimate of around 1 per 100,000,¹ showing variability in reported prevalence rates.

KSS is a multi-system disorder and can present differently in different people. KSS is defined by the following three features:¹

• onset before the age of 20, and
• CPEO, and
• changes in the back of the eye known as pigmentary retinopathy.

People with KSS also have at least one of the following conditions:¹

• heart issues, known as complete heart block
• high protein in spinal fluid
• trouble with balance, known as cerebellar ataxia
• being shorter than usual, known as short stature
• hearing loss
• dementia
• or endocrine disorders.

Symptoms of CPEO

Which include:

Impaired eye movements (ophthalmoplegia)

Ophthalmoplegia is a weakness of the muscles that move the eye. More specifically, external ophthalmoplegia affects the eye muscles responsible for movement. These muscles allow the eye to move in different directions, such as up, down, side to side, and in a circular motion. People with CPEO may have to turn their heads to see in different directions, especially as the ophthalmoplegia worsens.

Droopy eyelid(s) (ptosis)

Ptosis is when the upper eyelids droop, making it difficult to see properly and can affect one or both eyelids. As ptosis worsens, you may use your forehead muscles to try to lift your eyelids or lift your chin to see.

Pigmentary retinopathy

Pigmentary retinopathy is a condition where the retina, the part of the eye that senses light, gets damaged. This damage causes abnormal colouring in the retina, which can look like a “salt-and-pepper” pattern. Over time, this leads to poor night vision and progressive peripheral vision loss.

Heart conditions

Heart conditions, like heart block (cardiac conduction defects) and cardiomyopathy, are common in KSS.

• Heart block slows or blocks the signals that control your heartbeat. It can cause dizziness or fainting.
• Cardiomyopathy weakens and enlarges the heart muscle. It makes it harder for the heart to pump blood. This causes symptoms like shortness of breath and fatigue.

High protein in spinal fluid

This means there is more protein than usual in the fluid around the brain and spine, which can indicate an issue like inflammation or infection.

Cerebellar ataxia

This is when a person has difficulty keeping their balance and coordinating their movements because of problems in the part of the brain called the cerebellum.

Dementia

A condition where a person has trouble with memory, thinking, and daily activities because of changes in the brain.

Hearing loss

Hearing loss means not being able to hear well. Sensorineural hearing loss is a type of hearing loss caused by damage to the inner ear or the nerves that send sound signals to the brain.

Endocrine conditions

Endocrine problems can be the first symptom of KSS before other neurological symptoms show up. These problems happen in 35% to 67% of people with KSS and can include:

Diabetes mellitus

A condition where the body can’t properly control blood sugar levels, leading to high or low blood sugar.

Short stature

This means being shorter than usual because the body doesn’t make enough growth hormones, which are needed for normal growth. Without it, bones and muscles don’t grow as they should.

Low sex hormones (hypogonadotropic hypogonadism)

The body doesn’t make enough sex hormones due to issues with the brain’s hormone signals, affecting puberty and fertility.

Weak adrenal glands (adrenal insufficiency)

The adrenal glands don’t produce enough hormones like cortisol, leading to symptoms like fatigue, weakness, and low blood pressure.

Low parathyroid hormone (primary hypoparathyroidism)

The parathyroid glands don’t make enough hormones to regulate calcium levels in the blood, causing muscle cramps, tingling, and other symptoms.

Doctors who specialise in hormones are known as endocrinologists. Endocrinologists will monitor for these conditions and check for them regularly as they can often be treated.¹

Other signs and symptoms of KSS include:

• Dysphagia
• Low muscle tone (hypotonia)

For more information

Understand the signs and symptoms of mito

KSS is a genetic condition caused by genetic changes that affect metabolism,⁶ which is how the body converts food into energy and removes waste. This process relies on hormones and enzymes to run smoothly. When a genetic change disrupts this process, it impacts mitochondrial function. Mitochondria are responsible for producing the energy your body needs, and when they can’t do this properly, it can make it difficult for parts of your body, like your muscles or brain, to function the way they should.

In KSS, the eye muscles are particularly affected because they contain many mitochondria and are more sensitive to these genetic changes.⁷ This leads to eye problems such as drooping eyelids (ptosis) and difficulty moving the eyes (ophthalmoplegia).

About 9 out of 10 people with KSS are caused by DNA changes in the mitochondria (mtDNA) and inherited from our mother (maternally inherited). These are called Single Large Scale Mitochondrial Deletion Syndromes (SLSMDSs). The size and sequence of mtDNA deleted varies from person to person. One in three people with KSS have a 5 kilobase (kb) deletion, often referred to as the “common deletion (4977 base pair (bp))”.¹ This means mtDNA is missing a 4,977 bp segment.

A genetic change can occur randomly during conception. This means it is seen for the first time in a person and has not appeared in other family generations. This kind of change is called de novo, which means new.

SLSMDSs are usually de novo. Occurring during the formation of a mother's egg cells or in the early development of the embryo. There is usually no family history of mito.⁸ For someone with a SLSMDS, research suggests a low risk of passing it on to future generations.^8–10 Males with this mtDNA change cannot pass it on to their children.⁸

Within your cells, both healthy and changed mitochondria can exist. Known as heteroplasmy. Imagine it is like having good and faulty machinery. Sometimes, the faulty machinery doesn’t cause immediate problems. But when the change affects a large portion of mitochondria, symptoms can appear.

In a family, different organs can be affected differently. One family member might struggle with energy supply (due to the faulty machinery), while another seems fine. It’s all because of this uneven distribution of healthy and changed mitochondria. This can explain why the mtDNA deletion may not be found in blood tests. So other tests such as a muscle biopsy may be needed to confirm a diagnosis.

For more information

Learn more about the options for building your family

Other causes of KSS

Generally, KSS is not inherited. But, in rare cases, factors other than mtDNA deletions can cause KSS. These cases follow the inheritance pattern of the specific gene involved.

• If the genetic change is present in mtDNA, the mother passes it down maternally.
• For a genetic change in nuclear DNA (nDNA) to affect a child, both parents must carry it. This is an autosomal recessive pattern.

Other genes that may cause KSS

Mitochondrial DNA

• MT-TL1: This gene helps make a special molecule called transfer RNA (tRNA), which is like a little helper that brings the building blocks to make proteins in our cells. Specifically, it helps add an amino acid called leucine to proteins as they are being made.
• MT-TK: This gene helps make a special molecule called tRNA lysine, which is like a little helper that brings building blocks to make proteins in our cells.
• MT-ATP6: This gene is important for making energy in our cells. It helps create a molecule called ATP, which is like a battery that powers everything our cells do.
• MT-ND4: This gene is part of a big machine in our cells called complex I that makes energy by moving tiny particles called electrons.
• MT-ND6: This gene also helps with making energy in our cells. It works with MT-ND4 in the same big machine called complex I to help turn food into energy.

Nuclear DNA (nDNA)

Recycling DNA building blocks (nucleotide metabolism):

• RRM2B: This gene helps make the building blocks for DNA.

Making new mtDNA (synthesis of mtDNA):

• POLG: This gene helps make new copies of mitochondrial DNA.
• TWNK: This gene helps unwind the DNA so it can be copied.

Bringing in DNA building blocks (nucleotide import):

• ANT1: This gene helps bring the building blocks into the mitochondria.

For more information

Learn more about genetics and mito

Information to understand your diagnosis

Information to understand your child’s diagnosis

A diagnosis for KSS is based on your history, signs and symptoms, physical examination, as well as other testing.

Physical exam

During a physical exam, your eyes and nervous system will be examined. Your health professional will check your eye muscles. They will test your ability to focus on targets and move your eyes in different directions. Additionally, they may measure your ptosis.

Your health professional may also refer you for more testing, such as:

• A muscle biopsy may be needed. A muscle biopsy looks for “ragged red fibres” under a microscope, which is a sign of some types of mito, like KSS that may not be detectable in blood samples.
• Blood tests may be used to measure substances like lactate and pyruvate, as high levels of these can signal KSS. Blood tests can also be used to rule out other conditions. They look for the lack of specific antibodies for other conditions. These include myasthenia gravis and thyroid-related eye problems.
• A lumbar puncture may be used as many people with KSS have high protein levels and/or low levels of folate in their brain and spinal fluid. A lumbar puncture allows health professionals to check this.
• An electrocardiogram (ECG) checks your heart rhythm, or an echocardiogram (echo) may be required to look for heart muscle issues.
• Magnetic Resonance Imaging (MRI) or a Computed Tomography (CT) scan are noninvasive imaging methods that may be needed to detect brain abnormalities associated with KSS.
• Magnetic Resonance Spectroscopy (MRS) is another type of brain scan that looks specifically for lactate.

Genetic testing

If your doctor suspects KSS, they will arrange genetic testing to look for any changes associated with the condition.

Genetic testing for mitochondrial deletions is specific and known as Next-generation sequencing (NGS). NGS is a modern method used to read the order of DNA or RNA in a sample. Unlike older techniques that could only sequence one strand at a time, NGS can sequence many strands all at once, making it much faster and more efficient.¹

The process starts with preparing the sample by breaking the DNA or RNA into smaller pieces. These pieces are then sequenced simultaneously using advanced machines. Finally, the sequences are put together and analysed to identify any genetic changes.¹

NGS is the best method to find large deletions in mtDNA from blood samples. If blood tests are negative but KSS is still suspected, a muscle biopsy may be tested as some genetic changes might not show up in blood tests.¹ But sometimes, other samples like skin, hair, or urine, are needed due to heteroplasmy (see causes of KSS).

Genetic testing is highly specialised, and it may take up to three to four months to receive the results. Genetic counselling is important to discuss what these results mean for you and your family.

For more information

Learn more about genetics and mito

If you have KSS, you’ll likely need a team of health professionals to manage your care. Here are some health professionals you might work with:

• General Practitioner (GP): your main point of contact. They can help with referrals, and tests, and coordinate your care.
• Neurologist: specialises in nervous system disorders, and monitors progression.
• Ophthalmologist: Monitors ptosis, ophthalmoplegia and peripheral vision.
• Orthoptist: works with an ophthalmologist to test vision and uses specialised diagnostic tests to detect and examine the visual system's function.
• Cardiologist: accesses and monitors heart conditions.
• Endocrinologist: to address any metabolic or endocrine abnormalities, such as diabetes.
• Metabolic specialist: helps manage energy production issues. They help ensure your cells get the energy they need to function.
• Genetic Counselor: provides education and support for people with genetic health conditions.
• Audiologist: accesses and monitors with hearing loss.
• Physiotherapist: helps with mobility and strength.
• Speech Therapist: addresses and manages swallowing difficulties (dysphagia) if present.
• Occupational Therapist: assists with daily living activities and maintaining quality of life.
• Mental health professional: offers mental health and wellbeing support.

For more information

Information to build your care team

Information to build your child’s care team

For most people with mito, regular tests are important. These tests help monitor how mito is affecting you. Learn more about monitoring mito for adults, or children.

The following recommendations have been adapted from the Australian Patient Care Standards for mito:¹¹

Watching for serious illness (Critical care)

During a sudden illness, you must be monitored closely and regularly, and your lactate levels should be closely monitored. Lactate levels refer to the amount of lactic acid in your blood. Elevated levels of lactic acid can be harmful. But, monitoring the lactic acid in your blood (serum lactate) can help your health care team intervene early, to reduce the risk of serious illness.

Eye care (Ophthalmology)

If you have eye symptoms of KSS, it's essential to see an ophthalmologist for a thorough assessment. This includes:

• checking your visual acuity
• assessing your visual fields
• examining your eye movements
• assessing any drooping eyelids (ptosis).

If your vision is impaired, consider seeing a low-vision specialist. Surgery might be necessary for conditions like strabismus, ptosis, or cataracts.

Annual visits with your ophthalmologist are recommended for ongoing monitoring. This involves:

• checking for changes in your vision
• checking the health of your retina and macula
• measuring your intraocular pressure
• evaluating the health of your optic nerve

If you find it difficult to close your eyelids due to ptosis or after ptosis surgery,consider using methylcellulose eye drops or ointments to keep your eyes lubricated.

Brain and nerve care (Neurology)

Managing pain

Headaches and migraines are treated the same way for people with or without mito. If your migraines get worse or you notice new symptoms, it could mean something has changed with your health. Talk to your health professional if anything is different.

Muscle weakness (Myopathy)

Your muscle function may be evaluated, including strength and certain enzyme levels. Monitor any changes or worsening  symptoms. If you notice any changes, speak to your health professional. They may request blood tests to look for high levels of enzymes or look for other potential causes, which might involve a range of tests.

In case of muscle breakdown due to exercise or illness, known as rhabdomyolysis, there are standard treatments to follow. Exercise is beneficial, but it should be tailored to your needs and capabilities. Before starting any exercise program, your heart function should be checked to ensure it’s safe to proceed.

When managing myopathy as part of mito, it’s essential to be proactive about your health. It’s always best to discuss these aspects with your health professional to get advice that fits your situation. They can guide you on the right path to managing your condition effectively.

For children with KSS

Monitoring their developmental progress and cognitive status is important. Your health professional may use tools like the Griffiths scales. It can provide valuable insights during the early developmental stages.

As children with KSS reach 6 years of age, regular neuropsychological help is needed to customise care plans. Monitoring is recommended every two years or more frequently if there’s a change in cognitive abilities or behaviour.

If you see new symptoms or changes in your child's development, speak to your health professional. A referral to a developmental pediatrician and other health professionals can be considered. These professionals can work with your child's school to support their growth and development.

Staying active

For people with mito, moderate-intensity aerobic exercise is best. Aim for 70% of your maximum heart rate. This helps improve your baseline fitness. However, this is not recommended if you have cardiac issues. Always speak to your mito specialist and cardiologist before starting a new exercise regimen.

Physio and regular assessments can help maintain mobility and prevent complications. To create a personalised exercise plan, speak to a professional such as an exercise therapist or physiotherapist.

Heart care (Cardiology)

You may need an initial heart check-up, including an ECG, 24-hour ECG monitoring, and/or an echocardiogram. Annual ECGs are important to monitor your heart health. The frequency of other tests will be personalised based on your specific needs and family history.

For irregular heartbeats (conduction defects), treatments and procedures are available, such as a pacemaker, to help regulate your heartbeat. A pacemaker is a small, battery-powered device that's surgically implanted usually in the chest to send electrical signals to your heart to make sure it beats at the right pace.

Growth and hormone care (Endocrinology)

If you have diabetes, formally known as diabetes mellitus, it is important to manage your blood sugar within your target range. This will help prevent nerve damage and other diabetic-associated conditions.

Hearing care (Audiology)

Regular hearing checks are essential, especially for children who might need special tests. These assessments should be done initially and then every one to two years. Avoid loud noises to prevent worsening hearing loss, which might not be reversible. Some antibiotics, like aminoglycosides, can worsen hearing loss.

Monitor your hearing closely during serious illnesses or acute episodes. Digital hearing aids can help with moderate to severe hearing loss, while cochlear implants might be an option for very severe cases. Talk to your health professional about these options. Hearing loss can affect speech and learning, especially in children.

Getting the right support (Care coordination and social work)

Taking care of your mental health is just as important as managing physical symptoms when dealing with KSS. If you have any psychiatric symptoms, such as anxiety, depression or memory loss, speak to your health professional.

For children, it’s particularly important to watch for low self-esteem and anxiety. Addressing these feelings early can make a big difference in their emotional wellbeing.

Medicines to be used with caution

Certain medications can affect your muscles. They are:

• Statins for high cholesterol
• Metformin for blood sugar control
• Corticosteroids for inflammation like asthma
• Antiretrovirals for viral infections such as HIV

They should be used with caution. If you’re prescribed these, regular monitoring is crucial to avoid worsening your myopathy.

Other medications include:

• If you have optic atrophy or mtDNA depletion syndrome a seizure medication called vigabatrin should be used with caution.
• Valproate is used for the management of seizures and may be harmful (contraindicated). Especially for those with POLG genetic changes, due to its potential to worsen seizures and risk of liver failure.

Supplement considerations for KSS

There are some reports that certain supplements might help people with KSS. These include:¹

• co-enzyme Q10 (CoQ)
• carnitine
• thiamine
• riboflavin
• magnesium orotate
• alpha-lipoic acid

However, there isn’t enough evidence to prove that these supplements are beneficial for everyone with KSS. They are known to help in specific conditions, for example:

• Thiamine may be helpful when combined with a ketogenic diet for pyruvate dehydrogenase deficiency.
• CoQ may be beneficial for primary CoQ deficiency.¹

Before starting a new medication or supplement, always consult with your health professional.

Learn more about supplements and mito.

For more information

Access the Patient Care Standards for Mito

Mito Foundation provides information to help people affected by mito understand clinical trials and how to find opportunities that may be relevant to them.

Clinical trials help researchers test new ways to prevent, diagnose, treat and manage mito. Some trials test whether a treatment is safe and whether it may help people.
Other clinical studies may look at symptoms, diagnosis, genetics, quality of life, or how mito affects people over time.
Clinical trials are carefully planned. The therapies being studied may be at different stages. Trials may not be available for every type of mito, and not every trial will be right for you. Some trials are only open to people with a confirmed genetic diagnosis, specific symptoms, a certain age range, or the ability to attend study appointments.

Mito Foundation’s emerging therapies information explains therapies in development, how clinical trials work, and what you may wish to consider before taking part. You can also use the Therapy Finder to explore therapies in development and see what may be relevant to you.

Learn more about taking part in clinical trials
Use the Therapy Finder

Staying informed

One way to hear about opportunities to take part in clinical trials is to join the Mito Registry.

The Mito Registry helps connect people with research opportunities that may be relevant to them. It also helps Mito Foundation understand how many people in Australia are affected by different types of mito.

This information can help support future research, services and advocacy.

Join the Mito Registry

• National Organisation for Rare Disorders: KSS
• Genetic and Rare Diseases Information Centre: KSS
• MedlinePlus: Kearns-Sayre syndrome
• Muscular Dystrophy Association: Mitochondrial Myopathies

• Mito Support Community – Facebook group

As of June 2025, no active support groups dedicated to KSS were found in Australia.

• CPEO/KSS - Facebook group (UK)
• Kearns Sayre Syndrome & Chronic Progressive External Ophthalmoplegia – Facebook group (UK)