Kearns Sayre syndrome belongs to a group of mitochondrial DNA deletion syndromes, together with pearson syndrome and progressive external ophthalmoplegia (PEO). An onset of progressive ophthalmoplegia and pigmentary retinopathy before the age of 20, accompanied by cardiac and central nervous system abnormalities, are clinical hallmarks of this disorder. The diagnosis rests on clinical criteria, findings from muscle biopsies and biochemical tests, as well as genetic studies.
The clinical presentation of patients suffering from Kearns Sayre syndrome (KSS), in which spontaneous deletion of mitochondrial DNA occurs during embryogenesis, is quite specific and is comprised of a juvenile onset (before 20 years of age), progressive external ophthalmoplegia (PEO) and pigmentary retinopathy  . Several other features are frequently encountered, one of the most common being cardiac conduction abnormalities - left anterior fascicular block (with or without right bundle branch block), various degrees of atrioventricular (AV) block, long QT wave, torsades de pointes type of ventricular tachycardia and dilated cardiomyopathy are diagnosed in 50% of cases  . Sudden cardiac death preceded by syncope is seen in up to 20% of patients, stressing the need for an early diagnosis . Additionally, almost 40% of KSS patients have a short stature , while hearing loss, dementia, dysphagia, weakness of the limbs and ataxia originating from the cerebellum are additional symptoms   . Diabetes mellitus is an important endocrinopathy encountered in a significant proportion of patients, whereas thyroid and parathyroid abnormalities, as well as Addison's disease and growth hormone deficiency, have been observed in KSS  . Intolerance to exercise can be reported by many patients, and because of the wide spectrum of signs and symptoms that may be noted, the diagnosis is often delayed for a significant period of time  .
A detailed diagnostic workup is pivotal in order to make the diagnosis of KSS, especially when the presence of cardiac abnormalities can predispose to sudden cardiac arrest. Firstly, patient history should reveal the onset and course of symptoms, as young age is considered as mandatory criteria for KSS. A thorough physical examination, if conducted properly, can detect ataxia, arrhythmias, ptosis, visual deficits, hearing loss and weakness of the limbs. Ophthalmoscopy must be carried out to confirm retinal changes and ophthalmoplegia, while cardiac assessment must not be forgotten, and electrocardiography (ECG), as well as cardiac ultrasonography, are essential if KSS is suspected . However, a definite diagnosis is achieved through laboratory testing that notes very high levels of lactate and pyruvate in blood, especially after moderate exercise, abnormally high protein content in the cerebrospinal fluid (more than 100mg/dL), and markedly reduced activity of enzymes involved in the respiratory chain complex, such as citrate synthase . Clinical and biochemical suspicion toward KSS is confirmed by performing a muscle biopsy, which will reveal typical "ragged-red fibers" (RRFs) on gömöri trichrome stain, hyperactive fibers when using the succinate dehydrogenase stain and failure to stain both RRF and non-RRF fibers using cytochrome c oxidase (COX)  .