Kearns-Sayre syndrome
Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy characterized by a range of symptoms that can significantly impact an individual's quality of life. Typically manifesting before the age of twenty, KSS is associated with distinctive features such as progressive external ophthalmoplegia (PEO), which leads to difficulties in eye movement, and specific pigmentation changes in the eyes referred to as salt-and-pepper retinopathy. Additionally, patients may experience dysfunction in heart and skeletal muscles due to the underlying mitochondrial DNA mutations, which can progressively worsen over time.
The etiology of KSS involves deletions in mitochondrial DNA, which are inherited in a strictly maternal manner. Symptoms can vary widely, with some individuals experiencing minimal issues while others may face severe complications like muscle weakness, seizures, and impaired vision. Diagnosis typically involves a thorough medical history, physical examination, and various laboratory tests, including muscle biopsies and genetic testing. Although no specific cure exists for KSS, treatment focuses on managing symptoms through dietary supplements, physical therapy, and medications tailored to individual needs. Awareness of family medical history is crucial, as genetic factors can increase the risk of developing mitochondrial diseases.
Kearns-Sayre syndrome
ALSO KNOWN AS: Kearns-Sayre mitochondrial cytopathy; KSS; Leigh syndrome; mitochondrial DNA depletion syndrome; mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes; myoclonic epilepsy associated with ragged red fibers; mitochondrial myopathy; mitochondrial neurogastrointestinal encephalopathy; neuropathy, ataxia, and retinitis pigmentosa; Pearson syndrome; progressive external ophthalmoplegia (PEO)
DEFINITION Mitochondria are tiny structures in all cells that provide energy. Mitochondrial myopathies are a group of diseases that affect them. These diseases affect the nerves and muscles, among other systems. The severity of these diseases can vary greatly; some produce mild symptoms, and others have life-threatening conditions.
Kearns-Sayre syndrome (KSS) is one of the mitochondrial myopathies. The onset of this disease occurs before age twenty. Defining symptoms of KSS include salt and pepper pigmentation in the eye, eye movement problems (progressive external ophthalmoplegia, or PEO), and heart and skeletal muscle dysfunction. PEO may appear along with other mitochondrial disease symptoms, but it can be an independent syndrome. The onset of PEO occurs in adulthood. Its defining symptoms include eye movement difficulty. The onset of Leigh syndrome occurs at infancy. Defining symptoms of this form of mitochondrial myopathy include brain abnormalities that lead to muscle problems, seizures, uncoordinated muscle movement (ataxia), impaired vision and hearing, developmental delay, and poor control over breathing. The onset of mitochondrial DNA depletion syndrome occurs at infancy. Defining symptoms of this disease include muscle weakness and liver failure, floppiness, feeding difficulties, and developmental delay. The onset of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) occurs from childhood to adulthood. Defining symptoms include stroke-like episodes, migraine headaches, vomiting and seizures, muscle weakness, exercise intolerance, hearing loss, diabetes, and short stature. The onset of myoclonic epilepsy associated with ragged red fibers (MERRF) is from late childhood to adulthood. MERRF’s defining symptoms include myoclonus (jerky movements), seizures, muscle weakness, and uncoordinated muscle movement (ataxia). The onset of mitochondrial neurogastrointestinal encephalopathy (MNGIE) occurs before age twenty. Its defining symptoms include eye movement problems (PEO), drooping eyelid, limb weakness, digestive problems, and peripheral neuropathy. The onset of neuropathy, ataxia, and retinitis pigmentosa (NARP) occurs from early childhood to adulthood. Defining symptoms include uncoordinated muscle movement (ataxia) and degeneration of the retina in the eye, leading to loss of vision. The onset of Pearson syndrome occurs at infancy. Pearson syndrome causes severe anemia and pancreas problems. Survivors of this disease usually develop KSS. Individuals who suspect that they have mitochondrial myopathy should contact their doctors.
Risk Factors
Individuals who have a family member with the gene for mitochondrial myopathy are at risk of developing the disease. According to the US National Library of Medicine in 2022, Kearns-Sayre syndrome affected about 1.6 people out of 100,000.
Etiology and Genetics
Kearns-Sayre syndrome results from deletions in a gene in mitochondrial DNA known as OMIM 530000. Each muscle or nerve cell contains anywhere from several to more than one hundred copies of mitochondrial DNA, and each mitochondrial DNA molecule contains thirteen structural genes that encode protein components of respiratory chain complexes. Genes for transfer RNAs and ribosomal RNAs (components of mitochondrial protein synthesis) are also present. In patients with Kearns-Sayre syndrome, each cell may have a mixture of normal and mutant (deleted) mitochondrial DNA. The greater the ratio of mutant DNA to normal DNA, the more severe will be the symptoms. Since the deleted mitochondrial DNA often replicates faster than the normal form, the disease tends to be progressive as this ratio increases over time. Since mitochondrial genes affect respiratory chain function, the disease has the greatest effect on those tissues with the highest energy requirements, such as skeletal and cardiac muscles, nerve cells, and kidney cells.
Inheritance of mitochondrial DNA follows a pattern of strict maternal inheritance, since all of the mitochondria in a fertilized egg (zygote) come from the egg cell. Thus affected females will transmit the disease to all of their offspring, but affected males produce unaffected children.
Symptoms
Mitochondrial myopathies can cause a range of symptoms. Some people experience very few symptoms; others may experience the full range. Individuals who have any of the symptoms should not assume they are due to mitochondrial myopathy, as these symptoms may be caused by a number of conditions.
Individuals should tell their doctors if they have any of the symptoms, including muscle weakness, exercise intolerance, loss of hearing, seizures, lack of balance or coordination, progressive weakness, inability to move eyes, heart failure, learning deficits, and fatigue. Other symptoms include blindness, stroke-like episodes, droopy eyelids, vomiting, breathlessness, headache, nausea, dementia, diabetes, and muscle wasting.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history, and a physical exam will be done. A patient will also be asked about any family history of the disease.
Tests may include a muscle biopsy, a test that involves removing a small piece of muscle to look for abnormal levels of mitochondria or the presence of certain proteins and enzymes; a blood test that looks for abnormal levels of certain enzymes and other substances; and a genetic test, a blood test or muscle biopsy that tests for the presence of genetic mutations.
Treatment and Therapy
Individuals should talk with their doctors about the best plans for them. There is no specific treatment for these diseases. Symptoms can be treated.
Treatment options include the use of dietary supplements, which may help make energy in the cells. These supplements may include creatine, carnitine, and coenzyme Q10.
Physical therapy may be used to strengthen muscles and improve mobility. Some people may need devices like braces, walkers, or wheelchairs. Muscle weakness in the throat may require speech therapy. In some cases, respiratory therapy may be needed, which can include pressurized air treatment or the use of a ventilator. Medications are used to treat specific symptoms, such as seizures, pain, and diabetes.
Prevention and Outcomes
There are no known guidelines to prevent this condition.
Bibliography
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