eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Kearns-Sayre Syndrome: Differential Diagnoses & Workup

Author: Ewa Posner, MD, Consultant Pediatrician, Department of Pediatrics, University Hospital of North Durham, UK
Coauthor(s): Anna Purna Basu, BM, BCh, PhD, MA, MRCPCH, Registrar, Pediatric Neurology, Newcastle General Hospital; Clinical Research Associate, University of Newcastle upon Tyne, UK; 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
Contributor Information and Disclosures

Updated: Sep 15, 2008

Differential Diagnoses

Atrioventricular Block, Second Degree
Atrioventricular Block, Third Degree, Acquired
Failure to Thrive
Hypomelanosis of Ito
MELAS Syndrome
Pearson Syndrome

Other Problems to Be Considered

Other causes of ophthalmoplegia in combination with additional disorders
Chronic progressive external ophthalmoplegia

Workup

Laboratory Studies

  • Serum creatinine kinase levels may be within the reference range or moderately elevated.
  • Blood lactate and pyruvate levels are usually elevated.
  • In CSF, the lactate level is elevated, even if blood lactate levels are within the reference range. Kearns-Sayre syndrome raises the CSF protein level.
  • Although a polymerase chain reaction test performed on DNA from blood samples can reveal deletions in mtDNA, the best means of achieving definitive diagnosis is via analysis of a muscle biopsy specimen, with quantification of the level of deletion using Southern blot analysis.
  • Screening is recommended to exclude the endocrinologic abnormalities that occur in many patients. Screening methods may include tests to measure serum glucose levels, thyroid function, calcium and magnesium levels, and serum electrolyte levels. A combination of high sodium and low potassium levels can suggest hyperaldosteronism, which occurs in 3% of patients with Kearns-Sayre syndrome.

Imaging Studies

  • MRI of the brain has limited diagnostic use. MRI findings may be normal or show cerebral and cerebellar atrophy. T2-weighted MRI findings in subcortical white matter (with or without symmetric involvement) may demonstrate lesions with high signal intensity in the brainstem, globus pallidus, thalamus, and cerebellum, alone or in combination. Neurologic deficits and MRI findings have limited correlation.

Other Tests

  • ECG reveals cardiac conduction defects; measure the PR interval.
  • Electroretinography helps assess retinal degeneration.
  • Audiometry helps detect sensorineural deafness.

Procedures

  • Perform a lumbar puncture and measure protein and lactate levels in the CSF.
  • Muscle biopsy findings may show ragged red fibers using a modified Gomori 1-step trichrome stain. Ragged red fibers have abnormal aggregates of mitochondria that are subsarcolemmal. Muscle histochemistry results reveal deficiency of cytochrome c oxidase in these cells. However, ragged red fibers are also observed in muscle biopsy findings from other mitochondrial disorders and are not specific to Kearns-Sayre syndrome.

Histologic Findings

  • In patients with Kearns-Sayre syndrome, as in patients other mitochondrial encephalopathies, spongy degenerative changes occur in both the gray and white matter of the brain. Most changes in the white matter occur in the cerebrum and cerebellum; most gray matter changes occur in the brainstem. Neuronal loss is evident in the brainstem and cerebellum, with demyelination. Calcium deposits accumulate in the globus pallidus and thalamus.
  • Histologic studies of the heart show abnormalities of the conduction system. Large mitochondria with abnormal structure develop in both skeletal and heart muscles.

More on Kearns-Sayre Syndrome

Overview: Kearns-Sayre Syndrome
Differential Diagnoses & Workup: Kearns-Sayre Syndrome
Treatment & Medication: Kearns-Sayre Syndrome
Follow-up: Kearns-Sayre Syndrome
References
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References

  1. Tanji K, DiMauro S, Bonilla E. Disconnection of cerebellar Purkinje cells in Kearns-Sayre syndrome. J Neurol Sci. Jun 15 1999;166(1):64-70. [Medline].

  2. Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf). Jul 1992;37(1):97-103. [Medline].

  3. 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. Dec 1999;13 ( Pt 6):769-72. [Medline].

  4. Anan R, Nakagawa M, Miyata M, et al. Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects. Circulation. Feb 15 1995;91(4):955-61. [Medline]. [Full Text].

  5. Bosbach S, Kornblum C, Schroder R, Wagner M. Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain. May 2003;126(Pt 5):1231-40. [Medline]. [Full Text].

  6. Chinnery PF, DiMauro S, Shanske S, et al. Risk of developing a mitochondrial DNA deletion disorder. Lancet. Aug 14-20 2004;364(9434):592-6. [Medline].

  7. Chinnery PF, Turnbull DM. Mitochondrial DNA mutations in the pathogenesis of human disease. Mol Med Today. Nov 2000;6(11):425-32. [Medline].

  8. 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. Oct 1999;41(10):759-64. [Medline].

  9. Elson JL, Samuels DC, Turnbull DM, Chinnery PF. Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am J Hum Genet. Mar 2001;68(3):802-6. [Medline].

  10. Emma F, Pizzini C, Tessa A, et al. "Bartter-like" phenotype in Kearns-Sayre syndrome. Pediatr Nephrol. Mar 2006;21(3):355-60. [Medline].

  11. Finsterer J, Haberler C, Schmiedel J. Deterioration of Kearns-Sayre syndrome following articaine administration for local anesthesia. Clin Neuropharmacol. May-Jun 2005;28(3):148-9. [Medline].

  12. Moraes CT, DiMauro S, Zeviani M, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. May 18 1989;320(20):1293-9. [Medline].

  13. 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 July 9, 2008.

  14. Pijl S, Westerberg BD. Cochlear implantation results in patients with Kearns-Sayre syndrome. Ear Hear. Jun 2008;29(3):472-5. [Medline].

  15. Yamashita S, Nishino I, Nonaka I, Goto Y. Genotype and phenotype analyses in 136 patients with single large-scale mitochondrial DNA deletions. J Hum Genet. 2008;53(7):598-606. [Medline].

  16. Zeviani M, Moraes CT, DiMauro S, et al. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. 1988. Neurology. Dec 1998;51(6):1525 and 8 pages following. [Medline].

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Further Reading

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Keywords

Kearns-Sayre syndrome, KSS, ophthalmoplegia-plus syndrome, oculocraniosomatic syndrome, chronic progressive external ophthalmoplegia and myopathy, CPEO, chronic progressive external ophthalmoplegia with ragged red fibers, mitochondrial cytopathy, ophthalmoplegia, pigmentary degeneration of the retina, cardiomyopathy, progressive ophthalmoplegia, Pearson syndrome, mtDNA deletions, mitochondrial encephalopathy, short stature, hypoparathyroidism, bilateral sensorineural deafness, dementia, cataracts, proximal renal tubular acidosis, heart block, syncope, cardiac failure, hypogonadism

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Contributor Information and Disclosures

Author

Ewa Posner, MD, Consultant Pediatrician, Department of Pediatrics, University Hospital of North Durham, UK
Ewa Posner, MD is a member of the following medical societies: European Paediatric Neurology Society and Royal College of Paediatrics and Child Health
Disclosure: Nothing to disclose.

Coauthor(s)

Anna Purna Basu, BM, BCh, PhD, MA, MRCPCH, Registrar, Pediatric Neurology, Newcastle General Hospital; Clinical Research Associate, University of Newcastle upon Tyne, UK
Anna Purna Basu, BM, BCh, PhD, MA, MRCPCH is a member of the following medical societies: British Medical Association
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.

Medical Editor

Erawati V Bawle, MD, FAAP, FACMG, Director, Division of Genetic and Metabolic Disorders, Department of Pediatrics, Children's Hospital of Michigan; Professor (Clinician-Educator), Wayne State University School of Medicine
Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine
Margaret McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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