Kearns-Sayre Syndrome (KSS) is a rare, progressive neuromuscular disorder classified as a mitochondrial disease. Its root cause is the malfunction of the cell’s energy-producing structures. This complex condition typically begins before the age of 20, often presenting in childhood or adolescence. KSS is a severe form of chronic progressive external ophthalmoplegia that impacts the eyes, heart, brain, and endocrine system.
The Underlying Mitochondrial Dysfunction
KSS results from a specific problem within the mitochondria, the organelles responsible for generating most of the cell’s energy (ATP). The energy production process, oxidative phosphorylation, depends on genes encoded by mitochondrial DNA (mtDNA). KSS is caused by large-scale deletions within this circular mtDNA molecule.
These deletions, ranging from 1.1 to 10 kilobases, remove genes essential for the respiratory chain complexes that produce ATP. The most common anomaly is a 4,977 base pair deletion, often called the “common deletion.” This loss severely impairs the cell’s ability to create energy. This damage is most pronounced in tissues with high energy demands, such as the eye muscles, heart, and central nervous system.
The condition is usually sporadic, arising from a new mutation rather than being inherited. The mutation exists in a state called heteroplasmy, where some mitochondria contain deleted DNA while others remain normal. Symptoms manifest only when the proportion of abnormal mtDNA surpasses a certain threshold, which varies by organ. This explains why the disease affects multiple systems but often begins with ocular symptoms.
The Defining Clinical Features
A diagnosis of Kearns-Sayre Syndrome is based on a specific clinical triad, all features of which must be established before the age of 20. The first required feature is Progressive External Ophthalmoplegia (PEO), involving the gradual weakness and paralysis of the muscles that control eye movement. This often begins as bilateral drooping of the eyelids (ptosis), progressing to limit the eyes’ ability to move in all directions.
The second defining feature is Bilateral Pigmentary Retinopathy, a degeneration of the retina leading to visual impairment. This damage is visible upon examination as a characteristic “salt-and-pepper” pattern of pigmentation. This retinopathy can cause progressive vision loss and night blindness.
Beyond this obligate triad, KSS is a multisystem disorder that includes other serious features, with at least one additional condition typically required for confirmation. Cardiac conduction defects are among the most serious complications, often manifesting as a heart block that can lead to fainting or sudden death. This heart involvement occurs in about half of all cases and is the most significant factor influencing long-term survival.
Neurological involvement is common and frequently includes cerebellar ataxia, resulting in problems with coordination, balance, and gait. Patients may also exhibit sensorineural hearing loss and elevated protein levels in the cerebrospinal fluid (often exceeding 100 mg/dL). Endocrine disorders are also seen, including diabetes mellitus, hypoparathyroidism, and growth hormone deficiency.
Methods Used for Confirmation
Once KSS is suspected, specialized tests are performed to confirm the diagnosis and assess the extent of organ involvement. Genetic testing is central to confirmation, identifying the single, large-scale deletion in the mitochondrial DNA. DNA for this analysis is ideally extracted from muscle tissue, as the proportion of deleted mtDNA is often higher there than in blood cells.
A muscle biopsy is an important diagnostic tool, where the tissue sample is stained and examined under a microscope. A hallmark finding is the presence of “ragged-red fibers” (RRFs). These are muscle cells that appear abnormal due to an excessive accumulation of dysfunctional mitochondria, providing a direct visual sign of the underlying mitochondrial myopathy.
An Electrocardiogram (EKG) is used to monitor life-threatening cardiac complications, detecting and tracking the progression of heart block or other conduction abnormalities. Other laboratory tests include a lumbar puncture to analyze the cerebrospinal fluid (CSF), which frequently reveals a protein level greater than 100 mg/dL. Blood and CSF lactate and pyruvate levels may also be measured, as they are often elevated due to impaired energy metabolism.
Strategies for Symptom Management
Currently, there is no treatment that can cure KSS or reverse the underlying mitochondrial dysfunction. Management focuses entirely on supportive care and the prevention of life-threatening complications. The most critical intervention involves managing cardiac conduction defects. Due to the high risk of sudden cardiac death, a permanent pacemaker is strongly recommended for all patients with any evidence of heart block.
Ophthalmological care requires regular monitoring to manage the effects of PEO and pigmentary retinopathy. Surgical procedures, such as a frontal sling, may be used to mechanically lift the drooping eyelids (ptosis) to improve vision. Regular retinal examinations track the progression of the vision-impairing retinopathy.
Endocrine issues, such as diabetes and thyroid problems, are managed with standard hormone replacement therapies and medication. Nutritional support is also considered, including supplements like Coenzyme Q10, which is sometimes given to support mitochondrial function, although its effectiveness is variable. Other supportive measures include hearing aids for sensorineural deafness and physical therapy to maintain muscle strength and coordination.