Kearns-Sayre syndrome (KSS) is a rare, progressive genetic disorder. This condition primarily affects the muscles, eyes, and heart, though it can involve multiple organ systems. The defining feature of KSS is its onset, with symptoms typically appearing before an individual reaches 20 years of age. As a mitochondrial myopathy, KSS is characterized by muscle weakness and a progressive course.
The Genetic Basis of Kearns-Sayre Syndrome
The root cause of Kearns-Sayre syndrome lies in defects within the cell’s powerhouses, the mitochondria. Mitochondria possess their own small, circular strand of DNA (mtDNA), which contains genes essential for oxidative phosphorylation. This process generates most of the cell’s energy in the form of Adenosine Triphosphate (ATP). KSS is caused by large-scale deletions within the mtDNA. These deletions result in the loss of genetic codes necessary for producing proteins vital to energy generation, severely impairing ATP production.
In the vast majority of cases, the mutation is considered de novo, meaning it is a spontaneous event that is not inherited. The altered mtDNA is present alongside normal mtDNA within the cells, a state known as heteroplasmy. Symptoms only manifest when the proportion of mutated mtDNA crosses a certain threshold, which varies depending on the specific organ system. Tissues with high energy demands, such as muscle and nerve cells, are the most severely affected by this energy deficit.
Defining Clinical Manifestations
A diagnosis of Kearns-Sayre syndrome requires a specific triad of symptoms, all of which must have an onset before age 20. The first mandatory symptom is Chronic Progressive External Ophthalmoplegia (CPEO), involving weakness and eventual paralysis of the muscles controlling eye movement. This often leads to drooping eyelids (ptosis) and an inability to move the eyes laterally or vertically.
The second required feature is pigmentary retinopathy, a condition causing damage and degeneration to the retina. This damage often gives the retina a characteristic “salt-and-pepper” or speckled appearance. This condition can lead to vision problems, particularly difficulty seeing in low light or at night.
Beyond this mandatory triad, KSS involves significant systemic problems, notably affecting the cardiac, neurological, and endocrine systems. Cardiac conduction defects are a serious concern, as electrical signals regulating the heartbeat can become blocked, leading to heart block. This complication is potentially life-threatening and is a major determinant of the long-term outlook.
Non-ocular neurological involvement is also common, including cerebellar ataxia, which causes problems with balance and coordination. Patients frequently experience progressive sensorineural hearing loss. Other manifestations include muscle weakness in the limbs (proximal myopathy), short stature, and endocrine disorders like diabetes mellitus or hypoparathyroidism.
Establishing a Diagnosis
The diagnosis of Kearns-Sayre syndrome is established through clinical observation and specialized testing, starting with confirmation of the characteristic symptom triad. Physicians conduct a thorough ophthalmological exam to confirm the progressive external ophthalmoplegia and pigmentary retinopathy. Detailed testing often includes an electroretinogram to assess retinal function.
Genetic testing is a cornerstone of diagnosis, confirming the large-scale deletion in the mitochondrial DNA. This analysis is typically performed on blood or muscle tissue, as the deletion is often more easily detectable in muscle. A muscle biopsy may also be performed, which characteristically reveals abnormal cells known as “ragged-red fibers,” indicating mitochondrial dysfunction.
A cardiac evaluation is primary due to the high risk of heart block. An electrocardiogram (EKG) monitors the heart’s electrical activity and measures the PR interval to detect early conduction defects. Further tests may include an echocardiogram and a spinal tap to measure protein levels in the cerebrospinal fluid, which are often abnormally elevated.
Current Management Strategies and Long-Term Outlook
There is currently no cure or disease-modifying treatment available for Kearns-Sayre syndrome; management focuses on supportive care and monitoring complications. The primary concern is the risk of sudden cardiac death due to progressive heart block. Regular follow-up with a cardiologist is mandatory, and prophylactic pacemaker implantation is often recommended.
A multidisciplinary team addresses systemic issues. Ophthalmologists manage eye symptoms, sometimes using surgery to correct ptosis and improve the visual field. Hearing aids or cochlear implants may be used for sensorineural hearing loss.
Endocrine abnormalities like diabetes are managed with standard therapies. Physical therapy helps maintain muscle strength and function. Nutritional supplements, such as Coenzyme Q10, are sometimes suggested. The disease is progressive, and the long-term outlook is variable, largely depending on the severity of the cardiac involvement.