History

The following are noted in patients with Kearns-Sayre syndrome (KSS):

Muscle weakness
- Chronic and progressive decreased eye movements and ptosis
- Dysphagia
- Skeletal muscle weakness (proximal more than distal) and exercise intolerance
CNS dysfunction
- Ataxia
- Dementia, encephalopathy, or specific focal neuropsychological deficits
- Deafness
- Night blindness
Cardiac disease
- Syncope
- Palpitations
Symptoms of endocrine dysfunction
- Diabetes mellitus
- Menstrual irregularities, delayed puberty
- Poor growth, failure to thrive
- Seizures due to hypocalcemia (hypoparathyroidism)

Physical

In patients with Kearns-Sayre syndrome, signs are as follows:

Muscle weakness
- Proximal myopathy (difficulty rising from a squat)
- Ptosis (usually bilateral but may be symmetrical initially)
- External ophthalmoplegia (as is seen in the image below)
  
  Bilateral ptosis and external ophthalmoplegia. Top: patient looking straight ahead. Below: patient is being asked to look in the direction of the arrow in each case. Restriction of eye movements in each direction is demonstrated.
  View Media Gallery
CNS dysfunction
- Retinitis pigmentosa
- Cerebellar ataxia
- Cognitive deficits^[6]
- Cataracts
- Encephalopathy (in acute presentation with lactic acidosis)
Cardiac
- Bradycardia
- Congestive cardiac failure
Endocrine
- Short stature (38% of affected individuals)
- Hypogonadism (20% of affected individuals)
- Other (eg, signs of hypothyroidism)

Causes

See the list below:

Kearns-Sayre syndrome occurs secondary to deletions in mtDNA (see Pathophysiology).

Differential Diagnoses

Kozak I, Oystreck DT, Abu-Amero KK, et al. New observations regarding the retinopathy of genetically confirmed Kearns-Sayre syndrome. Retin Cases Brief Rep. 2016 Dec 19. [QxMD MEDLINE Link].
Berio A, Piazzi A. Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus) in Kearns-Sayre syndrome. Pediatr Med Chir. 2013 May-Jun. 35 (3):137-40. [QxMD MEDLINE Link].
Shemesh A, Margolin E. Kearns Sayre Syndrome. StatPearls. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Khambatta S, Nguyen DL, Beckman TJ, Wittich CM. Kearns-Sayre syndrome: a case series of 35 adults and children. Int J Gen Med. 2014. 7:325-32. [QxMD MEDLINE Link].
Lee SJ, Na JH, Han J, Lee YM. Ophthalmoplegia in Mitochondrial Disease. Yonsei Med J. 2018 Dec. 59 (10):1190-6. [QxMD MEDLINE Link]. [Full Text].
Bosbach S, Kornblum C, Schroder R, Wagner M. Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain. 2003 May. 126(Pt 5):1231-40. [QxMD MEDLINE Link]. [Full Text].
Jackson MJ, Schaefer JA, Johnson MA, Morris AA, Turnbull DM, Bindoff LA. Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients. Brain. Apr 1995. 118 (Pt 2):339-57. [QxMD MEDLINE Link].
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):1293-9. [QxMD MEDLINE Link].
Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf). 1992 Jul. 37(1):97-103. [QxMD MEDLINE Link].
Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome. Nature. Apr 1981. 290(5806):457-65. [QxMD MEDLINE Link].
Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for humanmitochondrial DNA. Nat Genet. Oct 1999. 23(2):147. [QxMD MEDLINE Link].
Schwartz M, Vissing J. Paternal inheritance of mitochondrial DNA. N Engl J Med. Aug 2002. 347(8):576-80. [QxMD MEDLINE Link].
Lin YF, Schulz AM, Pellegrino MW, Lu Y, Shaham S, Haynes CM. Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response. Nature. 2016 May 19. 533 (7603):416-9. [QxMD MEDLINE Link]. [Full Text].
OMIM. Kearns-Sayre syndrome. Online Mendelian Inheritance in Man Web site. Available at http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?530000. Accessed: April 7, 2009.
Goldstein A, Falk MJ, Adam MP, et al. Mitochondrial DNA Deletion Syndromes. GeneReviews. Updated 2019 Jan 31. [QxMD MEDLINE Link]. [Full Text].
Chinnery PF, DiMauro S, Shanske S, et al. Risk of developing a mitochondrial DNA deletion disorder. Lancet. 2004 Aug 14-20. 364(9434):592-6. [QxMD MEDLINE Link].
Lopez-Gallardo E, Lopez-Perez MJ, Montoya J, Ruiz-Pesini E. CPEO and KSS differ in the percentage and location of the mtDNA deletion. Mitochondrion. 2009 Sep. 9(5):314-7. [QxMD MEDLINE Link].
Remes AM, Majamaa-Voltti K, Karppa M, et al. Prevalence of large-scale mitochondrial DNA deletions in an adult Finnish population. Neurology. Mar/2005. 64(6):976-81. [QxMD MEDLINE Link].
Schaefer AM, McFarland R, Blakely EL, et al. Prevalence of mitochondrial DNA disease in adults. Ann Neurol. Jan 2008. 63(1):35-9. [QxMD MEDLINE Link].
Imamura T, Sumitomo N, Muraji S, et al. The necessity of implantable cardioverter defibrillators in patients with Kearns-Sayre syndrome - systematic review of the articles. Int J Cardiol. 2019 Mar 15. 279:105-11. [QxMD MEDLINE Link].
Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion. Dec 2008. 8(5-6):396-413. [QxMD MEDLINE Link].
Chu BC, Terae S, Takahashi C, et al. MRI of the brain in the Kearns-Sayre syndrome: report of four cases and a review. Neuroradiology. 1999 Oct. 41(10):759-64. [QxMD MEDLINE Link].
Pasquini L, Guarnera A, Rossi-Espagnet MC, et al. Spinal cord involvement in Kearns-Sayre syndrome: a neuroimaging study. Neuroradiology. 2020 Oct. 62 (10):1315-21. [QxMD MEDLINE Link]. [Full Text].
Anan R, Nakagawa M, Miyata M, et al. Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects. Circulation. 1995 Feb 15. 91(4):955-61. [QxMD MEDLINE Link]. [Full Text].
Filosto M, Tomelleri G, Tonin P, et al. Neuropathology of mitochondrial diseases. Biosci Rep. Jun 2007. 27(1-3):23-30. [QxMD MEDLINE Link].
Andrews RM, Griffiths PG, Chinnery PF, Turnbull DM. Evaluation of bupivacaine-induced muscle regeneration in the treatment of ptosis in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Eye. 1999 Dec. 13 ( Pt 6):769-72. [QxMD MEDLINE Link].
Sebastia R, Fallico E, Fallico M, Fortuna E, Lessa S, Neto GH. Bilateral lid/brow elevation procedure for severe ptosis in Kearns-Sayre syndrome, a mitochondrial cytopathy. Clin Ophthalmol. 2015. 9:25-31. [QxMD MEDLINE Link]. [Full Text].
Weitgasser L, Wechselberger G, Ensat F, Kaplan R, Hladik M. Treatment of Eyelid Ptosis due to Kearns-Sayre Syndrome Using Frontalis Suspension. Arch Plast Surg. 2015 Mar. 42 (2):214-7. [QxMD MEDLINE Link]. [Full Text].
Kornblum C, Broicher R, Walther E, et al. Cricopharyngeal achalasia is a common cause of dysphagia in patients with mtDNA deletions. Neurology. May 2001. 56(10):1409-12. [QxMD MEDLINE Link].
Pijl S, Westerberg BD. Cochlear implantation results in patients with Kearns-Sayre syndrome. Ear Hear. 2008 Jun. 29(3):472-5. [QxMD MEDLINE Link].
Zhu CC, Traboulsi EI, Parikh S. Ophthalmological findings in 74 patients with mitochondrial disease. Ophthalmic Genet. 2017 Jan-Feb. 38 (1):67-9. [QxMD MEDLINE Link].
Pineda M, Ormazabal A, Lopez-Gallardo E, et al. Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion. Ann Neurol. Feb 2006. 59(2):394-8. [QxMD MEDLINE Link].
Chinnery PF, Turnbull DM. Mitochondrial DNA mutations in the pathogenesis of human disease. Mol Med Today. 2000 Nov. 6(11):425-32. [QxMD MEDLINE Link].
S DiMauro, M Hirano. Mitochondrial DNA Deletion Syndromes. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1203/. Accessed: 1/4/09.
Finsterer J, Haberler C, Schmiedel J. Deterioration of Kearns-Sayre syndrome following articaine administration for local anesthesia. Clin Neuropharmacol. 2005 May-Jun. 28(3):148-9. [QxMD MEDLINE Link].
Finsterer J. Central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand. Oct 2006. 114(4):217-38. [QxMD MEDLINE Link].
Aure K, Ogier de Baulny H, Laforet P, Jardel C, Eymard B, Lombes A. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression?. Brain. Jun 2007. 130(Pt 6):1516-24. [QxMD MEDLINE Link].
Grady JP, Campbell G, Ratnaike T, Blakely EL, Falkous G, Nesbitt V. Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain. 2013 Nov 25. [QxMD MEDLINE Link].
Mitochondrial DNA defects. The Rare Mitochondrial Disease Service for Adults and Children. Available at http://www.mitochondrialncg.nhs.uk/pa-adviceforwomen.html. Accessed: May 6, 2012.

Media Gallery

Skeletal muscle stained for both cytochrome oxidase (COX) and succinic dehydrogenase (SDH), two mitochondrial respiratory chain enzymes. Fibers that stain only for SDH and are COX-negative appear blue. Original magnification X 50.
Bilateral ptosis and external ophthalmoplegia. Top: patient looking straight ahead. Below: patient is being asked to look in the direction of the arrow in each case. Restriction of eye movements in each direction is demonstrated.
Modified Gomori Trichrome stain showing ragged red fibres. These show red staining round the periphery as well as within the sarcoplasm, giving a speckled appearance. Of the two affected muscle fibres pictured here, the one on the right shows a more extreme degree of mitochondrial proliferation and also some degeneration/vacuolation than the one on the left.

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Author

Anna Purna Basu, BMBCh, PhD, MA, NIHR Career Development Fellow, Newcastle University; Pediatric Neurologist, Great North Children's Hospital, Royal Victoria Infirmary, UK

Anna Purna Basu, BMBCh, PhD, MA, NIHR is a member of the following medical societies: Academic Paediatrics Association, British Association of Childhood Disability, British Medical Association, British Neuroscience Association, British Paediatric Neurology Association, Royal College of Paediatrics and Child Health

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: EI SMART C.I.C.

Coauthor(s)

Ewa Posner, MD, MRCP Consultant Pediatrician, Department of Pediatrics, University Hospital of North Durham, UK

Ewa Posner, MD, MRCP is a member of the following medical societies: Royal College of Paediatrics and Child Health, European Paediatric Neurology Society

Disclosure: Nothing to disclose.

Robert McFarland, MA, MBBS, PhD, MRCP Department of Health/HEFCE Clinical Senior Lecturer and Consultant Paediatric Neurologist, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust

Disclosure: Nothing to disclose.

D M Turnbull, MBBS, PhD, MD Professor, Department of Neurology, University of Newcastle Upon Tyne, UK; Honorary Consultant Neurologist, Royal Victoria Infirmary, Newcastle Upon Tyne, UK

D M Turnbull, MBBS, PhD, MD is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Sections Kearns-Sayre Syndrome
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Kearns-Sayre Syndrome Clinical Presentation

History

Physical

Causes

References

Tables

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