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Kearns-Sayre Syndrome: for professionals


Prevalence1 to 3 per 100,000
InheritanceSporadic (due to somatic mutations in mtDNA), maternally inherited in some cases
Genes Involved (OMIM No.)Mitochondrial DNA (mtDNA) mutations, often large-scale deletions (#530000)
SymptomsProgressive external ophthalmoplegia, Visual disturbances, Photophobia, Metamorphopsia, Sensorineural hearing loss
Ocular FeaturesSalt and pepper retinopathy, Optic atrophy, Peripheral retinal pigmentary changes
Systemic FeaturesCardiac conduction defects, Diabetes mellitus, Growth hormone deficiency, Hypoparathyroidism, Cerebellar ataxia, Elevated cerebrospinal fluid protein, Renal tubulopathy (Fanconi syndrome)
Key InvestigationsOcular: Ophthalmic examination, Optical coherence tomography (OCT), Fundus autofluorescence (FAF), Electroretinogram (ERG), Electro-oculogram (EOG)
Systemic: Cardiovascular assessments (ECG, echocardiography), Endocrine assessments (blood tests for hormone levels), Neurological assessments (MRI, CSF analysis), Renal assessments (urinalysis, blood tests)
Molecular DiagnosisGenetic testing for large-scale deletions in mtDNA
ManagementOcular: Regular ophthalmic monitoring, Ptosis surgery, Low vision aids Systemic: Cardiovascular monitoring, Pacemaker implantation, Hormone replacement therapy, Diabetes management, Physical therapy, Audiological support, Nutritional support Genetic counselling, advice on family planning, emotional and practical support
Therapies under ResearchResearch on molecular mechanisms, potential gene therapies, and diagnostic techniques

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Clinical phenotype

Kearns-Sayre Syndrome (KSS) is a rare mitochondrial disorder characterised by progressive external ophthalmoplegia, pigmentary retinopathy, and systemic involvement including cardiac, endocrine, and neurological abnormalities. The onset is typically before the age of 20, and the disorder progresses slowly over time.1,2

Presenting features


  • Progressive External Ophthalmoplegia (PEO): Paralysis of the eye muscles leading to ptosis and restricted eye movements.3
  • Visual disturbances: Including nyctalopia (night blindness) and eventual peripheral visual field loss.4,5
  • Photophobia: Sensitivity to light.
  • Metamorphopsia: Distorted vision due to retinal changes.


  • Cardiac: Conduction defects such as complete heart block, often requiring pacemaker implantation.6
  • Endocrine: Diabetes mellitus, growth hormone deficiency, and hypoparathyroidism.7-9
  • Neurological: Cerebellar ataxia, elevated cerebrospinal fluid protein, and sensorineural hearing loss.10
  • Renal: Tubulopathy leading to Fanconi syndrome.


  • Salt and pepper retinopathy: Mottled pigmentation of the retina.1,2
  • Optic atrophy: Occasional optic nerve pallor due to progressive retinal degeneration.
  • Peripheral retinal changes: Progressive pigmentary changes in the peripheral retina.


Genes: Mutations in mitochondrial DNA (mtDNA), often large-scale deletions.

  • OMIM No.: #530000
  • Inheritance pattern: Sporadic (due to somatic mutations in mtDNA) but can be maternally inherited.
  • Function: Mitochondrial dysfunction due to deletions in mtDNA, leading to impaired oxidative phosphorylation.11-13

Further information about each gene can be found on OMIM and Medline Plus.

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Key investigations


  1. Ophthalmic examination: Ptosis, ophthalmoplegia, pigmentary retinopathy.14
  2. Optical Coherence Tomography (OCT): Retinal thinning, cystoid macular oedema, and pigmentary changes.
  3. Fundus Autofluorescence (FAF): Areas of hypo- and hyper-autofluorescence corresponding to regions of retinal atrophy and pigment deposits.15,16
  4. Electrophysiological testing:
    • Electroretinogram (ERG): Reduced or absent rod and cone responses, with electronegative waveform indicating inner retinal dysfunction.
    • Electro-oculogram (EOG): Reduced light peak to dark trough ratio, indicating RPE dysfunction.
  5. Genetic testing: Large-scale deletions in mtDNA, commonly involving several mitochondrial genes.


  1. Cardiovascular Assessments:
    • Echocardiography and Electrocardiogram (ECG): Conduction defects such as complete heart block, cardiomyopathy, and arrhythmias.15
  2. Endocrine Assessments:
    • Blood ests: Hyperglycaemia, low growth hormone levels, and hypoparathyroidism with low calcium and high phosphate levels.
  3. Neurological Assessments:
    • MRI and Cerebrospinal Fluid (CSF) analysis: Elevated CSF protein levels, cerebellar atrophy, and white matter changes on MRI.17,18
  4. Renal Assessments:
    • Urinalysis and blood tests: Evidence of tubulopathy such as aminoaciduria, glycosuria, and electrolyte imbalances.

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A definitive diagnosis of Kearns-Sayre Syndrome involves integrating clinical features, genetic testing results, and comprehensive ocular and systemic evaluations.

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Differential Diagnoses

Differential diagnoses include other mitochondrial disorders such as chronic progressive external ophthalmoplegia (CPEO), and syndromes with similar ocular and systemic manifestations like myasthenia gravis.

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The management of Kearns-Sayre Syndrome requires a multidisciplinary approach to address its multisystemic manifestations and prevent complications.


  1. Regular ophthalmic monitoring: To track disease progression and manage complications.
  2. Ptosis surgery: To correct severe ptosis and improve visual function. This will be done through referral to oculoplastic surgeons.1,2
  3. Low vision aids: To assist patients with visual impairment.


  1. Cardiovascular Monitoring (by cardiology team):
    • Regular ECGs and echocardiograms to monitor cardiac function.
    • Pacemaker implantation for significant conduction defects.19
  2. Endocrine Management (by endocrine team):
    • Hormone replacement therapy for endocrine deficiencies.
    • Insulin or oral hypoglycaemic agents for diabetes management.
  3. Neurological Support (by neurology team):
    • Physical therapy for ataxia.
    • Audiological support for hearing loss.
  4. Nutritional Support (by dieticians):
    • Management of electrolyte imbalances due to renal tubulopathy.

Family management and counselling

Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Genetic counsellors and Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients and their parents in clinic. They provide emotional and practical support to help patients and parents deal with the diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist centre

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive comprehensive management of their condition (genetic testing and genetic counselling) and to have the opportunity to participate in clinical research. In the UK, patient can also be referred to the Mitochondrial services in Queens Square, London.

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Current research

Research on Kearns-Sayre Syndrome focuses on understanding the molecular mechanisms, developing potential gene therapies, and improving diagnostic techniques. Clinical trials investigating new treatments and management strategies aim to enhance outcomes and quality of life for affected individuals.

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Further information and support

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  1. Shemesh A, Margolin E. Kearns-Sayre Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482341/
  2. Nguyen MTB, Micieli J, Margolin E. Teaching NeuroImages: Kearns-Sayre syndrome. Neurology. 2019 Jan 29;92(5).
  3. Tsang SH, Aycinena ARP, Sharma T. Mitochondrial Disorder: Kearns-Sayre Syndrome. Adv Exp Med Biol. 2018;1085:161-162.
  4. Lee SJ, Na JH, Han J, Lee YM. Ophthalmoplegia in Mitochondrial Disease. Yonsei Med J. 2018 Dec;59(10):1190-1196.
  5. Finsterer J, Zarrouk-Mahjoub S. Kearns-Sayre syndrome is genetically and phenotypically heterogeneous. Pediatr Med Chir. 2018 May 29;40(1).
  6. Darsee JR, Miklozek CL, Heymsfield SB, Hopkins LC Jr, Wenger NK. Mitral valve prolapse and ophthalmoplegia: a progressive, cardioneurologic syndrome. Ann Intern Med. 1980 Jun;92(6):735-741.
  7. Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf). 1992 Jul;37(1):97-103.
  8. Bachynski BN, Flynn JT, Rodrigues MM, Rosenthal S, Cullen R, Curless RG. Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome. Ophthalmology. 1986 Mar;93(3):391-396.
  9. Pellock JM, Behrens M, Lewis L, Holub D, Carter S, Rowland LP. Kearns-Sayre syndrome and hypoparathyroidism. Ann Neurol. 1978 May;3(5):455-458.
  10. Drachman DA. Ophthalmoplegia plus. The neurodegenerative disorders associated with progressive external ophthalmoplegia. Arch Neurol. 1968 Jun;18(6):654-674.
  11. Saldaña-Martínez A, Muñoz ML, Pérez-Ramírez G, Montiel-Sosa JF, Montoya J, Emperador S, Ruiz-Pesini E, Cuevas-Covarrubias S, López-Valdez J, Ramírez RG. Whole sequence of the mitochondrial DNA genome of Kearns Sayre Syndrome patients: Identification of deletions and variants. Gene. 2019 Mar 10;688:171-181.
  12. Moraes CT, DiMauro S, Zeviani M, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. 1989 May 18;320(20):1293-1299.
  13. Leveille AS, Newell FW. Autosomal dominant Kearns-Sayre syndrome. Ophthalmology. 1980 Feb;87(2):99-108.
  14. Mullie MA, Harding AE, Petty RK, Ikeda H, Morgan-Hughes JA, Sanders MD. The retinal manifestations of mitochondrial myopathy. A study of 22 cases. Arch Ophthalmol. 1985 Dec;103(12):1825-183.
  15. Davis JC, Reiffel JA, Behrens M, Rowland L, Mascitelli R, Seplowitz A. Optic neuritis and heart block in Kearns-Sayre syndrome. N Y State J Med. 1981 Aug;81(9):1364-1368.
  16. Eagle RC Jr, Hedges TR, Yanoff M. The atypical pigmentary retinopathy of Kearns-Sayre syndrome. A light and electron microscopic study. Ophthalmology. 1982 Dec;89(12):1433-1440.
  17. Nakagawa E, Hirano S, Yamanouchi H, Goto Y, Nonaka I, Takashima S. Progressive brainstem and white matter lesions in Kearns-Sayre syndrome: a case report. Brain Dev. 1994 Sep-Oct;16(5):416-418.
  18. Kuriyama M, Suehara M, Marume N, Osame M, Igata A. High CSF lactate and pyruvate content in Kearns-Sayre syndrome. Neurology. 1984 Feb;34(2):253-255.
  19. Trivedi M, Goldstein A, Arora G. Prophylactic pacemaker placement at first signs of conduction disease in Kearns-Sayre syndrome. Cardiol Young. 2018 Dec;28(12):1487-1488.

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Updated on June 3, 2024
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