Kearns-Sayre syndrome is a multisystem mitochondrial disease characterized by the obligate triad of onset before the age of 20, progressive external ophthalmoplegia, and pigmentary retinopathy plus at least one of the following: cardiac conduction block, cerebrospinal fluid protein greater than 100 mg/dl, and cerebellar ataxia. The disorder is usually caused by single large-scale deletions of mitochondrial DNA (mtDNA). The authors review the clinical features and molecular pathogenesis of this unusual disease and put special emphasis on reports on the heterogeneous response to growth hormone therapy in Kearns-Sayre syndrome.
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• Kearns-Sayre syndrome is a multisystemic disorder defined by the triad of chronic progressive external ophthalmoplegia, retinitis pigmentosa, and onset before 20 years of age.
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• Kearns-Sayre syndrome is usually a result of single, large-scale deletion mutations of mitochondrial DNA.
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• Although Kearns-Sayre syndrome is typically sporadic, affected women with a large-scale deletion of mitochondrial DNA have a 4% to 11% risk of transmitting the mutation to a child.
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• In Kearns-Sayre syndrome, progressive cardiac conduction block is common and can be fatal; therefore, timely placement of a cardiac pacemaker can extend lifespan.
Historical note and terminology
In 1958, Kearns and Sayre reported two patients with the clinical triad of "retinitis pigmentosa, external ophthalmoplegia, and complete heart block" (30). For years, many physicians did not accept the existence of Kearns-Sayre syndrome; in the late 1960s, Dr. David Drachman lumped neurodegenerative disorders with progressive external ophthalmoplegia as "ophthalmoplegia plus" (15). In the late 1970s, Berenberg and colleagues reported five new patients, and reviewed 30 literature cases with the triad of clinical features described by Kearns and Sayre. Berenberg and his colleagues further noted that the syndrome was sporadic, began before the age of 20, and was frequently accompanied by elevated cerebrospinal fluid protein (07). In 1983, Rowland and colleagues proposed a new clinical definition that included these features (56). In 1988, large-scale deletions of mitochondrial DNA were discovered as the underlying gene defect in Kearns-Sayre syndrome patients (25; 76; 26).