Kearns-Sayre syndrome: Description, Causes and Risk Factors:
Kearns-Sayre Syndrome is a rare neuromuscular disorder characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), leading to chronic inflammation, progressive degeneration, and wearing away of certain eye structures (pigmentary degeneration of the retina); and heart disease (cardiomyopathy) such as heart block. Other findings may include muscle weakness, short stature, hearing loss, and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). In some cases, Kearns-Sayre Syndrome may be associated with other disorders and/or conditions.
Kearns-Sayre Syndrome belongs to a group of rare neuromuscular disorders known as mitochondrial encephalomyopathies. Mitochondrial encephalomyopathies are disorders in which a defect in genetic material arises from a part of the cell structure that releases energy (mitochondria), causing the brain and muscles to function improperly (encephalomyopathies). In these disorders, abnormally high numbers of defective mitochondria are present. In approximately 80 percent of cases of Kearns-Sayre Syndrome, tests will reveal missing genetic material (deletion) involving the unique DNA in mitochondria (mtDNA).
The inheritance of the mitochondrial genome is maternally, because during fertilization, the sperm tail, which contains the mitochondria, is displaced during the penetration of the ovule. Thus, it is not made part of the mitochondrial DNA of the zygote. Mitochondria are cytoplasm structures responsible for the production of intracellular adenosine triphosphate, which is necessary to supply energy for various metabolic functions. Tissues with high energy demand such as muscle and nervous system are particularly vulnerable to mitochondrial dysfunction.
Evidence that disease pathogenesis may be caused by defective RNR (ribonucleotide reductase) assembly is given. RRM2B screening should be considered early in the differential diagnosis of adults with multiple mtDNA (mitochondrial deoxyribonucleic acid) deletions.
The phenotypic expression depends directly on the number of mutations in alleles and systems affected, directly interfering directly in the phenotype and severity of the syndrome. The cardiac conduction disturbance is responsible for high mortality syndrome. It is estimated that the ratio is 1.6 cases per 100,000 population.
Multiple organ systems are affected in KSS, predominantlythe CNS, skeletal muscle & heart. It's characterized bythe obligatory triad of: onset before age 20; pigmentaryretinopathy & PEO (progressive external ophthalmoplegia). In addition at least one of the followingfeatures are seen: cardiac conduction block, CSF protein>100mg/dl,cerebellar ataxia.
The cardiac conduction defects andarrhythmia canoccur at any time during the disease course. Endocrinedisturbances which are associated include diabetes mellitus,hypothyroidism
, growth retardationand short stature; and hypogonadism, all due to the respective hormonal deficiencies.
Due to the large spectrum of clinical manifestations, theKSS has several differential diagnoses, among these othersyndromes mitochondrial encephalomyopathy, CCB andophthalmopathy. The most widely accepted diagnosticcriteria in the literature are the triad: progressive externalophthalmoplegia, pigmentary retinopathy and CCB. Thispatient had all the classic manifestations of the syndrome,the muscle biopsy confirm the genotypic diagnosis, butwould not add information for treatment and outcome.The biopsy of skeletal muscle identifies the ragged-redcells (red fibers torn), and is specific for diagnosis ofmitochondrial myopathies, plus the phenotype, the classic triad concludes the diagnosis of KSS. The techniquefor amplification of mitochondrial DNA by polymerasechain reaction (PCR), allows the diagnosis without performingthe biopsy.
The management aspect of this classic neuromuscular disorder is disappointing. Ubiquinone or CoE Q10 which is essential for the normal mitochondrial respiration may be tried. Though it may improve the cardiac function and exercise tolerance; it has no effect on ophthalmoplegia, ptosis or pigmentary retinopathy. Thiamine, Folic acid & L-carnitine have been tried to improve the metabolic failure. But a pacemaker insertion is important if a conduction deficit is present which will prevent the occurrence of sudden death. From the ophthalmologic side, the only management procedures are; a muscle surgery for strabismus and a sling surgery for ptosis.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.