Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 20 peer-reviewed journal articles Updated
Medical Genetics

Confirming the Diagnosis: Tests and Procedures

At a Glance

Kearns-Sayre syndrome (KSS) is diagnosed by finding large-scale mitochondrial DNA deletions, often requiring a muscle biopsy if blood tests are negative. A complete diagnostic workup also includes checking spinal fluid and performing baseline screenings for the heart, eyes, and endocrine system.

The journey to a Kearns-Sayre Syndrome (KSS) diagnosis often involves several different types of tests. Because KSS is a multisystem disorder, doctors use a combination of genetic testing, biochemical markers, and clinical exams to confirm the diagnosis and establish a baseline for your care [1][2].

The Genetic “Gold Standard”

The definitive way to confirm KSS is to find a large-scale deletion in your mitochondrial DNA (mtDNA) [3][4].

The Blood vs. Muscle Dilemma

One of the most confusing parts of the KSS diagnosis is that a blood test may come back “normal” even if you have the disease. This happens because of tissue heteroplasmy [3].

  • Blood cells divide very quickly. Over time, the body may naturally “select” against the deleted mitochondria in the blood, making them disappear from your circulation [3].
  • Muscle cells do not divide quickly. Therefore, the deleted mitochondria stay in the muscle tissue for your entire life [3][5].

If your doctor strongly suspects KSS but your blood work is negative, a muscle biopsy is often the next step to find the deletion and look for “ragged red fibers”—a classic sign of mitochondrial damage under the microscope [5][6].

Supportive “Clues” in the Body

While genetic testing provides the “final answer,” other tests help build the case for KSS:

  • Cerebrospinal Fluid (CSF) Protein: A lumbar puncture (spinal tap) often shows very high protein levels in KSS, frequently above 100 mg/dL [7][8]. This is a hallmark supportive finding that helps doctors rule out other neurological conditions [2].
  • Cerebrospinal Fluid (CSF) Folate: Recent research has shown that KSS patients often have low levels of 5-MTHF (a form of folate) in their spinal fluid, which can contribute to neurological decline if left untreated [9][10].
  • Brain MRI: Imaging of the brain often shows specific patterns, such as leukodystrophy (changes in the brain’s white matter) or cerebellar atrophy (shrinking of the balance center of the brain) [11][12].

Your Diagnostic Checklist

A full workup for KSS is about more than just getting a name for the condition; it is about ensuring every part of your body is safe. Ensure your medical team has completed the following baseline evaluations:

  • [ ] Genetic Testing: Using Next-Generation Sequencing (NGS) to look for large-scale mtDNA deletions in blood or muscle [4][6].
  • [ ] Cardiac Screening: An EKG and a Holter monitor (a 24-hour heart rhythm recording) to check for life-threatening heart block [13][14].
  • [ ] Ophthalmology Exam: A dilated eye exam to check for pigmentary retinopathy [15][1].
  • [ ] Hearing Test: An audiometry exam to check for sensorineural hearing loss [16][2].
  • [ ] Endocrine Labs: Blood tests to check for diabetes, hypoparathyroidism (calcium regulation), and growth hormone levels [17][18].
  • [ ] Neurology Baseline: An assessment of balance and coordination (ataxia) and a brain MRI [12][8].
  • [ ] Lumbar Puncture: Measuring CSF protein and importantly, CSF folate (5-MTHF) levels to detect cerebral folate deficiency [8][9].

Having these baseline results is vital because they allow your doctors to monitor for any changes over time and intervene early when needed [19][20].

Common questions in this guide

Why might my KSS genetic blood test be negative if I have the condition?
Blood cells divide quickly, and over time, your body can naturally clear out the cells with damaged mitochondrial DNA. Because of this, a blood test may look normal, requiring a muscle biopsy to confirm the diagnosis since muscle cells hold onto the damaged mitochondria.
What is the purpose of a muscle biopsy for Kearns-Sayre syndrome?
A muscle biopsy is used to look for large-scale deletions in your mitochondrial DNA when blood tests are inconclusive. Under a microscope, pathologists also look for "ragged red fibers," which are a classic sign of mitochondrial damage in KSS.
Why do doctors perform a lumbar puncture (spinal tap) when diagnosing KSS?
A spinal tap checks for elevated protein levels in your cerebrospinal fluid, which is a hallmark sign of Kearns-Sayre syndrome. Doctors also check for low folate levels in the spinal fluid, which can cause neurological issues if not treated.
What baseline tests are needed after a Kearns-Sayre syndrome diagnosis?
A complete baseline workup should include an EKG and Holter monitor for your heart, a dilated eye exam, an audiometry test for hearing, a brain MRI, and blood tests to check your endocrine function. These tests establish a baseline so doctors can monitor for any changes over time.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.If my blood test for mtDNA deletions was negative, when should we schedule a muscle biopsy?
  2. 2.What was the protein level in my cerebrospinal fluid, and how does that support the KSS diagnosis?
  3. 3.Can we review my baseline EKG for signs of 'fascicular block' or other early conduction issues?
  4. 4.Which specific endocrine labs (like PTH, glucose, and growth hormone) are being checked as part of my baseline workup?
  5. 5.Does my brain MRI show any characteristic white matter changes or signs of cerebellar atrophy?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (20)
  1. 1

    A rare case of Kearns-Sayre syndrome in a 17-year-old Venezuelan male with bilateral ptosis as the initial presentation.

    Leal M, Dhoble C, Lee J, et al.

    Oxford medical case reports 2016; (2016(3)):34-6 doi:10.1093/omcr/omw007.

    PMID: 26949540
  2. 2

    Unusual Phenotype and Disease Trajectory in Kearns-Sayre Syndrome.

    Finsterer J, Winklehner M, Stöllberger C, Hummel T

    Case reports in neurological medicine 2020; (2020()):7368527 doi:10.1155/2020/7368527.

    PMID: 32181031
  3. 3

    Ophthalmoplegia in Mitochondrial Disease.

    Lee SJ, Na JH, Han J, Lee YM

    Yonsei medical journal 2018; (59(10)):1190-1196 doi:10.3349/ymj.2018.59.10.1190.

    PMID: 30450853
  4. 4

    Clinical Phenotype and Genetic Features of a Pair of Chinese Twins with Kearns-Sayre Syndrome.

    Guo L, Wang X, Ji H

    DNA and cell biology 2020; (39(8)):1449-1457 doi:10.1089/dna.2019.5010.

    PMID: 32609007
  5. 5

    Management of Ptosis in Kearns-Sayre Syndrome: A Case Report and Literature Review.

    Moustaine MO, Azemour Z, Mohammed F, et al.

    Archives of plastic surgery 2024; (51(2)):182-186 doi:10.1055/a-2207-7587.

    PMID: 38596148
  6. 6

    Expanding the Genetic and Phenotypic Spectrum of Kearns-Sayre Syndrome: A Case Report.

    Messina C

    Cureus 2025; (17(5)):e84293 doi:10.7759/cureus.84293.

    PMID: 40524992
  7. 7

    Exophthalmos in Kearns-Sayre syndrome.

    Tauber J, Polla DJ, Park S

    Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 2019; (23(5)):295-297 doi:10.1016/j.jaapos.2019.05.005.

    PMID: 31158487
  8. 8

    Kearns-Sayre syndrome with rare imaging finding of SLC25A4 Mutation.

    Zhao H, Shi M, Yang F, Yang X

    Neurosciences (Riyadh, Saudi Arabia) 2022; (27(2)):111-115 doi:10.17712/nsj.2022.2.20210123.

    PMID: 35477912
  9. 9

    Kearns-Sayre syndrome presenting with fanconi syndrome: a case report.

    Lu Y, Jian S, Qian M, et al.

    Translational pediatrics 2025; (14(5)):1059-1064 doi:10.21037/tp-2025-138.

    PMID: 40519735
  10. 10

    Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics.

    Salvador CL, Oppebøen M, Vassli AØ, et al.

    Pediatric neurology 2023; (143()):68-76 doi:10.1016/j.pediatrneurol.2023.02.016.

    PMID: 37018879
  11. 11

    Kearns-Sayre syndrome: expanding spectrum of a "novel" mitochondrial leukomyeloencephalopathy.

    Moscatelli M, Ardissone A, Lamantea E, et al.

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2022; (43(3)):2081-2084 doi:10.1007/s10072-022-05881-8.

    PMID: 35031921
  12. 12

    Kearns-Sayre syndrome with restricted diffusion in subcortical white matter and extraocular muscle atrophy.

    Matsukawa M, Maeda M, Tanaka F, et al.

    Radiology case reports 2025; (20(6)):2646-2650 doi:10.1016/j.radcr.2025.02.088.

    PMID: 40151283
  13. 13

    Progressive Conduction Disease in a Mitochondrial Disorder.

    Amaro T, Bueno S, Guirão C, et al.

    JACC. Case reports 2026; 107749 doi:10.1016/j.jaccas.2026.107749.

    PMID: 42171571
  14. 14

    Prophylactic pacemaker placement at first signs of conduction disease in Kearns-Sayre syndrome.

    Trivedi M, Goldstein A, Arora G

    Cardiology in the young 2018; (28(12)):1487-1488 doi:10.1017/S1047951118001609.

    PMID: 30326976
  15. 15

    Teaching NeuroImages: Kearns-Sayre syndrome.

    Nguyen MTB, Micieli J, Margolin E

    Neurology 2019; (92(5)):e519-e520 doi:10.1212/WNL.0000000000006861.

    PMID: 30635486
  16. 16

    Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a TCF4 Trinucleotide Repeat, Commonly Associated with Fuchs Endothelial Corneal Dystrophy?

    Dudakova L, Skalicka P, Davidson AE, et al.

    Genes 2021; (12(12)) doi:10.3390/genes12121918.

    PMID: 34946867
  17. 17

    Fatal pneumonia in a patient with Kearns-Sayre syndrome case report and literature review.

    Zhang J, Song Z, Zhou H, et al.

    Frontiers in medicine 2025; (12()):1575384 doi:10.3389/fmed.2025.1575384.

    PMID: 40823579
  18. 18

    A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review.

    Kang YX, Wang YJ, Zhang Q, et al.

    Andrologia 2017; (49(8)) doi:10.1111/and.12711.

    PMID: 27709644
  19. 19

    Kearns-Sayre syndrome presenting with progressive external ophthalmoplegia and third-degree atrioventricular block diagnostic challenge in resource-limited settings: a case report.

    Azibte GT, Ayalew ZS, Molla BA, et al.

    Journal of medical case reports 2025; (19(1)):127 doi:10.1186/s13256-025-05086-5.

    PMID: 40114248
  20. 20

    Kearns-Sayre syndrome: Two case reports and a review for the primary care physician.

    Richmond C, Powell L, Brittingham ZD, Mancuso A

    Journal of family medicine and primary care 2023; (12(4)):792-795 doi:10.4103/jfmpc.jfmpc_1790_22.

    PMID: 37312792

This page provides educational information about diagnostic testing for Kearns-Sayre Syndrome. It is not a substitute for professional medical advice, diagnosis, or evaluation by a neuromuscular specialist or geneticist.

Get notified when new evidence is published on Kearns-Sayre syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.