Kearns-Sayre Syndrome

Kearns-Sayre syndrome is a rare condition that mainly affects the eyes, heart, and muscles, caused by problems in the tiny energy-producing structures within body cells. Most people develop symptoms before age 20, and while there is no cure, early diagnosis and supportive care can help manage the condition and improve quality of life.

Table of contents

• What is Kearns-Sayre syndrome?
• Other names for this condition
• How common is it?
• What causes Kearns-Sayre syndrome?
• How is it inherited?
• Symptoms and effects on the body
• How is it diagnosed?
• Treatment and management
• Outlook and prognosis

What is Kearns-Sayre syndrome?

Kearns-Sayre syndrome (KSS) is a rare disease that affects many parts of the body, especially the eyes, heart, and muscles^[1]. It is named after Thomas P. Kearns and George Pomeroy Sayre, who first described the disease in 1958^[1]. The condition belongs to a group of disorders called mitochondrial diseases, which happen when the energy-producing structures inside body cells don’t work properly^[1].

Mitochondria are tiny rod-like structures found in almost every cell of the body. They act as “energy factories,” producing about 90% of the energy needed to support body function and growth^[1]. Mitochondria use oxygen to convert fuel from the food you eat into energy your cells can use. When mitochondria are abnormal or damaged, they fail to produce enough energy, and the body cannot work properly^[1].

Kearns-Sayre syndrome is defined by three main features: symptoms starting before age 20, progressive external ophthalmoplegia (PEO), which means weakness or paralysis of the eye muscles, and pigmentary retinopathy, an unusual pattern of pigment changes in the back of the eye^[2][3]. In addition, people with KSS have at least one of the following: heart rhythm problems, high protein levels in the fluid around the brain and spinal cord, or difficulty with coordination and balance^[2][7].

Other names for this condition

Kearns-Sayre mitochondrial cytopathy, Oculocraniosomatic syndrome, Chronic progressive external ophthalmoplegia with myopathy, Mitochondrial ocular myopathy

How common is it?

Kearns-Sayre syndrome is very rare. An estimated 1 to 3 people out of every 100,000 have the disease^[1][2]. The condition can affect both men and women^[1].

What causes Kearns-Sayre syndrome?

KSS happens due to a genetic change in mitochondrial DNA (mtDNA)^[1]. Although most DNA is packaged in structures called chromosomes within the cell’s control center (nucleus), mitochondria have their own small amount of DNA that contains genes essential for normal mitochondrial function^[2].

People with Kearns-Sayre syndrome have a single, large deletion of mtDNA, ranging from 1,000 to 10,000 DNA building blocks. The most common deletion removes 4,997 building blocks, which includes twelve mitochondrial genes^[2]. The cause of this deletion in affected individuals is unknown^[2]. Approximately 90% of cases are sporadic, meaning they occur by chance during pregnancy, with the most common deletion accounting for more than one-third of cases^[3].

These mtDNA deletions result in the loss of genes important for mitochondrial protein formation and energy production. This impairment affects all steps of the energy-making process, and cells don’t get enough energy^[2]. Researchers have not determined exactly how these deletions lead to the specific signs and symptoms of KSS, although the features are probably related to a lack of cellular energy. It has been suggested that eyes are commonly affected because they are especially dependent on mitochondria for energy^[2].

How is it inherited?

Kearns-Sayre syndrome is generally not inherited, but arises from changes in the body’s cells that occur after conception. This type of change is called a somatic mutation and is present only in certain cells^[2]. Usually, the genetic changes that cause KSS happen as a baby develops during pregnancy. These genetic changes occur in the mitochondria^[1].

Rarely, this condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing baby, only mothers pass mitochondrial DNA to their children^[2][15]. This genetic disorder can be passed down from mothers, but may also occur without a family history^[1]. Genetic testing may help to determine if the mutation was inherited or not^[1].

Symptoms and effects on the body

The symptoms of Kearns-Sayre syndrome can vary widely, but generally start before the age of 20 and first affect the eyes^[1][15]. Over time, the disease may cause blindness^[1]. The condition progressively worsens, leading to a range of health issues that often involve the eyes, heart, muscles, and ability to think and reason^[1].

Eye problems

Early symptoms include difficulty seeing, especially in dark environments, due to damage to the retina, the light-sensitive layer at the back of the eye^[1]. People with KSS have drooping eyelids (ptosis) and difficulty moving the eyes due to weakness or paralysis of the eye muscles^[2][3]. This condition, called progressive external ophthalmoplegia, means the eye muscles gradually become weaker until there is complete immobility^[4].

Affected individuals also have an eye condition called pigmentary retinopathy, which results from breakdown of the retina that gives it a speckled and streaked appearance, sometimes described as “salt-and-pepper” pigmentation^[2][7]. This retinopathy may cause loss of vision, including night blindness and difficulty seeing in low light^[2][15].

Heart problems

People with KSS often have abnormalities of the electrical signals that control the heartbeat, called cardiac conduction defects^[2]. Heart block is a problem with the electrical signals that control the heartbeat and is one of the most serious complications^[15]. In a study of 35 patients with Kearns-Sayre syndrome, cardiovascular features included heart block in 31% of patients, conduction delays in 66%, loss of consciousness in 17%, and sudden cardiac death in 11%^[6]. Heart block can cause death in 20 percent of patients^[4][13].

Muscle and movement problems

People with KSS may experience muscle weakness in their limbs, particularly proximal muscle weakness affecting muscles closest to the body^[2][6]. Problems with coordination and balance cause unsteadiness while walking, a condition called ataxia^[2].

Other symptoms

Additional symptoms may include^{[2][4][6][15]:}

• Hearing loss or deafness
• Short stature
• Kidney problems
• A deterioration of thinking abilities (dementia)
• Abnormally high levels of protein in the fluid that surrounds and protects the brain and spinal cord
• Hormonal disorders, such as diabetes, growth hormone deficiency, or problems with other hormone-producing glands
• Seizures (though these are infrequent)

When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. The abnormal muscle cells contain an excess of structures called mitochondria and are known as “ragged-red fibers”^[2][3].

• Eyes (retina, eye muscles, eyelids)
• Heart
• Skeletal muscles
• Brain and spinal cord
• Ears
• Kidneys
• Hormone-producing glands

How is it diagnosed?

Diagnosis of Kearns-Sayre syndrome involves a combination of clinical evaluation, imaging studies, laboratory tests, and genetic testing^[15]. Getting an accurate diagnosis is important so you or your child can receive appropriate care for KSS^[1].

The doctor will conduct a physical examination to assess muscle strength, eye movements, and other symptoms^[15]. An eye exam checks for retinal changes and other eye problems^[15]. An electrocardiogram (ECG) assesses heart function and can identify electrical conduction problems^[15].

Blood tests may show elevated levels of lactate and pyruvate. Lactate levels in the fluid around the brain and spinal cord (cerebrospinal fluid or CSF) are elevated even if blood lactate levels are normal. CSF protein levels are very frequently elevated^[6]. Blood creatinine kinase level may be within the normal range or moderately elevated^[6].

In young children, single large-scale deletions may be detectable in blood. Alternatively, diagnosis may be established by muscle biopsy with specialized testing and mitochondrial DNA analysis for major rearrangements^[6]. Genetic testing helps identify mutations in mitochondrial DNA^[15].

Screening is recommended to exclude hormonal abnormalities that occur in many patients. Doctors measure serum electrolyte, glucose, calcium, magnesium, and plasma cortisol levels, as well as thyroid function^[6].

Magnetic resonance imaging (MRI) of the brain may reveal changes in the white matter of the brain, along with involvement of other brain structures^[6]. These tests help confirm the diagnosis and rule out other conditions that might cause similar symptoms^[15].

Treatment and management

There is currently no cure for Kearns-Sayre syndrome, and no effective way to treat mitochondria abnormalities^[4][10]. Treatment is generally supportive and aims to manage symptoms and improve quality of life. Early diagnosis and ongoing treatment can help you or your child manage symptoms for an improved quality of life^[1].

Heart care

The most essential aspect of management is regular and long-term follow-up with heart specialists (cardiologists)^[4]. Early diagnosis and periodic electrocardiogram (ECG) are important since heart block can cause death in 20 percent of patients^[4][13]. Conduction problems like heart block may be treated with a pacemaker, a device that helps control the heartbeat^[4]. Early pacemaker implantation can be of great benefit and offer a longer life expectancy in many patients^[4][13].

Because of the risk of serious heart complications during surgery, one study suggests that implantable cardioverter defibrillators and formal studies of the heart’s electrical system should be considered in patients with the syndrome^[6][10].

Eye care

There is typically no treatment for limitation in eye movement^[4]. Surgery to correct drooping eyelids (ptosis) may be performed, but should occur only in centers with specialists in eye surgical procedures^[10]. Use of supportive devices, such as eyelid crutches or surgery, can address drooping eyelids^[15]. Regular eye exams help monitor and manage vision problems^[15].

Other supportive care

Management of KSS involves multiple specialties depending on the organs involved^[4]. Other consultations may include audiology, ophthalmology, endocrinology, neurology, and neuropsychiatry^[4]. Hearing aids may be required for hearing loss^[4]. Hormonal abnormalities can be treated with drugs^[4][15].

Physical therapy helps maintain muscle strength and mobility^[15]. Exercise may help patients with muscle weakness. Exercise that causes muscle contraction can lead to growth of muscle cell precursors that contain low levels of mutant DNA, potentially increasing the proportion of normal DNA to mutant DNA^[10].

Supplementation with coenzyme Q10 may be indicated^[10]. Surgical management may be needed if significant swallowing difficulties are present^[10].

Outlook and prognosis

KSS is a slowly progressive disorder^[4][13]. The condition worsens over time, leading to a range of health issues^[1]. The prognosis for individuals with KSS varies depending on the severity and the number of organs involved^[4][13].

Early diagnosis and periodic electrocardiogram are important since heart block can cause death in 20 percent of patients. Early pacemaker implantation can be of great benefit and offer a longer life expectancy in many patients^[4][13].

In the future, potential treatment may attempt to inhibit mutant mitochondrial DNA replication or encourage replication of normal mitochondrial DNA^[10]. The most promising approach for treatment in the future will be to alter replication or destroy abnormal mitochondria^[4][13]. Research is ongoing to better understand the genetic causes of Kearns-Sayre syndrome and to develop potential treatments. Scientists are exploring therapies that might improve mitochondrial function and slow the progression of the condition^[15].