This article includes discussion of Kearns-Sayre syndrome, KSS, familial Kearns-Sayre syndrome, and PEO-plus. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
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 1 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 corneal involvement and hypomagnesemia (which may have therapeutic implications), as well as the finding in a C elegans model of mtDNA deletion disorders that activation of the mitochondrial unfolded protein response caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics.
• Kearns-Sayre syndrome is usually a result of single, large-scale deletion mutations of mitochondrial DNA.
• 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.
• 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 2 patients with the clinical triad of "retinitis pigmentosa, external ophthalmoplegia, and complete heart block" (Kearns and Sayre 1958). 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" (Drachman 1975). In the late 1970s, Berenberg and colleagues reported 5 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 (Berenberg et al 1977). In 1983, Rowland and colleagues proposed a new clinical definition that included these features (Rowland et al 1983). In 1988, large-scale deletions of mitochondrial DNA were discovered as the underlying gene defect in Kearns-Sayre syndrome patients (Holt et al 1988; Zeviani et al 1988; Holt et al 1989).
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