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Kearns-Sayre syndrome (KSS) exact prevalence is unknown, but has been estimated at 1/125,000.

The disease often presents in childhood with the hallmark ocular symptoms of ptosis, pigmentary retinopathy and PEO, followed by the progressive occurrence of several other signs, depending on the tissue distribution of the molecular anomaly. The most frequently associated features include bilateral sensorineural deafness, heart involvement (cardiomyopathy, cardiac conduction defect), central nervous system involvement (cerebellar ataxia, dysarthria, bilateral facial weakness, intellectual deficit), skeletal muscle myopathy, intestinal disorders, endocrine disorders (delayed puberty, hypoparathyroidism, diabetes), and renal failure. The disease progresses slowly, over decades, with new symptoms appearing and previous symptoms slowly worsening. A very few cases of Pearson syndrome have progressed into KSS.

KSS is caused by deletions of large portions of mitochondrial DNA (mtDNA), resulting in the loss of genes involved in the oxidative phosphorylation pathway. Deletions are heteroplasmic (i.e. a single cell can harbor both deleted and normal DNA molecules). Symptoms only appear if the proportion of abnormal DNA is high. The abnormal DNA threshold depends on the organ (e.g. about 60% for the skeletal striated muscle). Exceptional cases of KSS may be observed in the absence of a typical single large mtDNA deletion. They may be due either to point mutations located in the mtDNA encompassing tRNA genes or in nuclear genes involved in mtDNA maintenance (i.e. RRM2B).

Clinical diagnostic criteria of the disorder include the triad of progressive external ophthalmoplegia, pigmentary retinopathy, and onset before 20 years of age, plus at least one of the followings: heart block, cerebellar symptoms, or cerebrospinal fluid protein levels above 100 mg/dl. Apart from clinical features, muscle pathology and molecular genetic analysis can play a great role in the diagnostic workup. Muscle pathology showed ragged-red fibers (RRF), ragged-blue fibers (RBF), or cytochrome c-oxidase (COX)-negative fibers in almost all patients. Diagnosis can be confirmed by the detection of a large deletion of mtDNA (1.3-10 kb) in a clinically or morphologically affected tissue (usually skeletal muscle).

Differential diagnoses include any disease caused by large mtDNA deletions or with an overlapping clinical picture, such as Pearson syndrome or maternally-inherited progressive external ophthalmoplegia.

Prenatal diagnosis is usually not performed.

Most cases of KSS are sporadic. Deletions of mtDNA are only exceptionally transmitted from one generation to the next. Men do not transmit their mtDNA to their offspring. The risk of a woman, carrying a large size mtDNA deletion, transmitting the deletion to her child has been estimated to be less than 4%. The exceptional cases of KSS due to causes other than a large size mtDNA deletion follow the transmission associated with the gene involved (maternal transmission in the case of mtDNA point mutations or autosomal recessive in the case of nuclear gene mutations).

Treatment of KSS is supportive. Regular follow-up with a cardiologist is recommended. In those with high-grade heart block, a permanent pacemaker/implantable cardioverter-defibrillator device may be suggested and improves the prognosis. Hearing aids may be given to those with sensorineural deafness. Supplementation with coenzyme Q10 has been beneficial in some cases. Ophthalmologic manifestations may be treated by surgery but there is a high risk of recurrence and possible ocular complications.

The prognosis essentially depends on the number of organs involved and, in each of them, on the proportion of the abnormal mtDNA. In the majority of cases, life expectancy can be normal with appropriate support.