What is Kearns-Sayre Syndrome?
Kearns-Sayre syndrome (KSS) is a specific type of a condition known as chronic progressive external ophthalmoplegia (CPEO). To put it simply, it’s a disease that affects some of your body features and mostly your eye muscles.
KSS is diagnosed when three things happen: the symptoms start before the person turns 20, they have CPEO, and they display an eye condition called pigmentary retinopathy which affects the color and functioning of the eyes. In addition to these, individuals suffering from KSS also exhibit at least one of the following conditions: complete heart block (an issue with the electrical signals in the heart), high protein levels in cerebrospinal fluid (the fluid in your spinal cord and brain), cerebellar ataxia (a condition that affects movement coordination), being shorter than average, hearing loss, memory loss, and abnormalities in the body’s hormone-producing glands.
What Causes Kearns-Sayre Syndrome?
About 90% of cases of KSS, or Kearns-Sayre syndrome, occur without any known cause. This is often due to a large-scale removal of certain parts of mitochondrial DNA (the DNA found in the part of a cell called the mitochondria, which helps in producing energy). These deletions can range from 1.1 to 10 kilobases (a unit of measurement for DNA). The most frequent deletion is known as the “common 4977 bp deletion”, and it’s responsible for more than one-third of cases.
Risk Factors and Frequency for Kearns-Sayre Syndrome
KSS, or Kearns-Sayre Syndrome, is an uncommon disease. Its exact number of cases is not known, but research shows that in Finland, about 1.6 out of every 100,000 people have this condition.
Signs and Symptoms of Kearns-Sayre Syndrome
Kearns-Sayre Syndrome (KSS) is a medical condition that results in several symptoms. Here are some of the common clinical signs:
- Persistent External Ophthalmoplegia: This involves a type of muscle weakness that affects the eyes, leading to droopy eyelids and problems moving the eyes.
- Pigmentary Retinopathy: This condition affects the retina at the back of the eye. It is characterized by pigment changes in the retina, resulting in vision problems. These issues, including night blindness or blurry vision, occur in approximately 40% to 50% of patients. The condition initially involves the back of the eyes and shows a characteristic ‘salt-and-pepper’ pattern of pigment grouping.
- Cardiac Conduction Disturbances: Patients with KSS may develop heart rhythm abnormalities at any point. These can range from minor prolongation of the PR interval (a measure of time on an ECG) to more serious blocks in the electrical signals within the heart, which can increase risk of stroke or sudden death.
- Non-Ocular Muscle Weakness: KSS can also affect other muscles, not just those in the eyes. Muscles in the face, which influence the ability to open and close the eyelids, can be affected. Some KSS patients may also have difficulties with swallowing, as well as weakness of the neck, shoulder, and distance muscles.
- Non-muscular Neurologic Dysfunction: KSS may lead to other neurological problems such as cerebellar ataxia (lack of muscle coordination), sensorineural hearing loss (deafness due to nerve damage), neuropathy (nerve damage causing weakness, pain, or numbness), and intellectual difficulties.
- Endocrine Disorders: Hormone-related problems can sometimes be the first symptom of KSS. These can occur in 35% to 67% of patients and include conditions like diabetes, short stature, lack of growth hormone, hypogonadotropic hypogonadism (low levels of sex hormones), adrenal insufficiency (hormone shortage from adrenal glands), and primary hypoparathyroidism (low levels of parathormone from parathyroid glands).
Testing for Kearns-Sayre Syndrome
When doctors suspect patients of having Kearns-Sayre Syndrome (KSS), a rare genetic disorder, they prefer to use a method called next-gen sequencing of our body’s cellular power plants, our mitochondria, found in our blood cells. This method helps identify any missing segments in the DNA of our mitochondria. However, if the results don’t match the patient’s symptoms, they may need to sequence the mitochondrial DNA in the muscle, as sometimes the mutations are specific to certain tissues and are not present in the blood. This additional search is necessary because very low levels of mixed populations of normal and disease-causing molecules (heteroplasmy) in the blood can sometimes lead to incorrect negative results.
Many KSS patients experience an increase of protein in their spinal fluid, so doctors might perform a lumbar puncture, commonly known as a spinal tap, to test this. Cerebral folate deficiency can also occur in KSS, potentially contributing to white matter brain disease (leukoencephalopathy) and cognitive symptoms, so it’s important for doctors to measure the levels of a B-vitamin derivative (5-methyltetrahydrofolate) in the spinal fluid of all patients.
Although brain imaging alone cannot confirm a diagnosis of KSS, because its findings are not confirmed as being indicative of the disease, it can be useful in detecting leukoencephalopathy, a condition that affects the white matter in the brain. This means an MRI of the patient’s brain is usually conducted.
The extent of abnormalities in the brain detected by the MRI often reflects the level of impact on the central nervous system. These abnormalities can show up as unusually bright areas in certain parts of the brain in the MRI scans. This is an indication of damage caused by KSS.
In addition, changes in brain metabolism, indicative of damaged mitochondria or neuron loss, can be seen in patients with KSS through a particular type of MRI scan known as MR spectroscopy.
Finally, some people with KSS may also develop heart disease, so cardiovascular magnetic resonance, a type of heart scan, may be used to help diagnose this. This scan can help identify structural changes in the heart muscle, which can assist doctors in diagnosing heart issues related to KSS.
Treatment Options for Kearns-Sayre Syndrome
When caring for patients with Kearns-Sayre syndrome (KSS), a rare genetic condition that affects various parts of the body, the main focus is on supportive treatments to manage symptoms. Folic acid supplements may be suggested for those who have low levels of this vital nutrient in their cerebrospinal fluid (the fluid that surrounds the brain and spinal cord). Additionally, hormone replacement therapy can help manage specific hormonal conditions associated with KSS, and in severe cases, a cardiac pacemaker may be needed for patients with heart rhythm issues.
Some patients with double vision may benefit from strabismus surgery, a procedure that repairs misaligned eyes. Those with droopy eyes, a condition known as ptosis, might have surgery to place a small device called a frontalis sling to raise their eyelids. For individuals experiencing hearing loss, cochlear implants can be utilized to stimulate the auditory nerve and enable the perception of sound.
Patients with KSS are frequently recommended to have various health checks throughout the year, such as yearly heart tests (ECG and echocardiography), 24-hour heart rhythm monitoring (Holter monitoring), hearing tests (audiometry), and hormonal evaluations.
Looking ahead, researchers are exploring promising new treatments. Since patients with KSS often have a mix of healthy and mutated DNA (known as heteroplasmy), one emerging therapy aims to enhance the function of mitochondria, the energy powerhouses of our cells, by reducing the amount of mutated DNA. In one model, an enzyme called ZFN targets and destroys the mutated DNA, thereby increasing the ratio of healthy to mutated DNA.
Anti-oxidants, specifically a mitochondrial antioxidant called CoQ 10 or ubiquinone, are commonly used in the management of KSS. EPI-743, another antioxidant related to CoQ 10, is currently being explored in clinical trials as another potential treatment for this syndrome.
What else can Kearns-Sayre Syndrome be?
When a patient shows symptoms of CPEO (Chronic Progressive External Ophthalmoplegia), doctors need to make sure the symptoms are not actually caused by other similar conditions. These can include the following:
- Isolated Chronic Progressive External Ophthalmoplegia (CPEO)
- Oculopharyngeal Muscular Dystrophy
- Myotonic Dystrophy
- Isolated Oculopharyngeal Myopathy
- Mendelian Chronic Progressive External Ophthalmoplegia (CPEO) – typically associated with multiple deletions of mtDNA such as POLG
