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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Medical Genetics

The Biology of Energy: Mitochondrial Deletions

At a Glance

Kearns-Sayre Syndrome (KSS) is caused by a large-scale deletion in mitochondrial DNA, which limits the energy your cells can produce. This lack of cellular power primarily impacts high-energy organs like the eyes, heart, and brain, with severity depending on the amount of damaged mitochondria.

To understand Kearns-Sayre Syndrome (KSS), it helps to look inside your cells. Every cell in your body has hundreds of tiny structures called mitochondria. These are the “energy factories” of the cell, responsible for turning the food we eat into the energy our organs need to function [1][2].

Key Terms to Know

  • mtDNA (Mitochondrial DNA): The separate “instruction manual” used only by the mitochondria.
  • Ptosis: Drooping of the upper eyelids due to muscle weakness.
  • Heteroplasmy: The mix of healthy and damaged mitochondria in a single cell or tissue.
  • Heart Block: A problem with the electrical system of the heart, causing it to beat too slowly or skip beats.

The Genetic “Instruction Manual”

Mitochondria are unique because they have their own set of DNA, separate from the DNA found in the rest of the cell. Think of this mitochondrial DNA (mtDNA) as the instruction manual for building and running the energy factory [1][3].

In KSS, a single, large-scale deletion occurs. This means a significant chunk of that instruction manual is missing [1][3]. Without those instructions, the factory cannot produce energy efficiently. This lack of energy is what leads to the symptoms of KSS [2][4].

The Concept of Heteroplasmy

A common question is: If I have this deletion, why isn’t every part of my body affected in the same way? The answer lies in a concept called heteroplasmy [5].

Most cells contain a mix of “healthy” mitochondria (with complete manuals) and “deleted” mitochondria (with missing manuals). Heteroplasmy refers to the ratio of deleted mitochondria to healthy ones [5][6].

  • If a tissue (like the skin) has a low percentage of deleted mitochondria, it may function perfectly fine.
  • If a tissue has a high percentage of deleted mitochondria, the energy factories will fail, and symptoms will appear [5][7].

Because these percentages can vary widely between your heart, your brain, and your eyes, each organ may be affected differently [6][8].

Why the Heart, Brain, and Eyes?

In any city, the buildings that use the most electricity (like a hospital or a factory) are the first to suffer during a power shortage. Your body is the same. The heart, brain, and eyes are “high-energy” tissues [2][9].

  • The Eyes: The muscles that move your eyes and the retina that processes light are constantly working and require a massive, steady stream of energy [10][4].
  • The Heart: Your heart never rests; it needs constant energy to maintain its electrical rhythm and pump blood [11][12].
  • The Brain: Balance, coordination, and hearing all require high-speed electrical signals that are very energy-intensive [13][14].

The SLSMDS Spectrum

KSS is not an isolated disease but part of a group called Single Large-Scale mtDNA Deletion Syndromes (SLSMDS) [15][16]. These conditions are all caused by the same type of genetic deletion, but they look different based on when they start:

  1. Pearson Syndrome: Usually begins in infancy and primarily affects the bone marrow (causing severe anemia) and the pancreas [17][18].
  2. Kearns-Sayre Syndrome (KSS): Begins before age 20 and involves the eyes, heart, and brain [13][10].
  3. Chronic Progressive External Ophthalmoplegia (CPEO): This is often a milder form where the symptoms are mostly limited to the eye muscles [16].

Interestingly, a person may “transition” along this spectrum. For example, some babies who survive Pearson syndrome may go on to develop the symptoms of KSS as they get older [15][19]. Knowing where you sit on this spectrum helps your medical team predict what systems might need more attention in the future.

Common questions in this guide

What is a mitochondrial DNA deletion?
A mitochondrial DNA deletion means a significant part of the mitochondrial instruction manual is missing. Without these instructions, your cells' energy factories cannot produce power efficiently, which leads to the symptoms of Kearns-Sayre Syndrome.
Why does Kearns-Sayre Syndrome primarily affect the eyes, heart, and brain?
These specific organs require constant, massive amounts of cellular energy to function properly. When mitochondrial DNA is damaged and energy production drops, these high-energy tissues are the first to experience issues and fail.
What does heteroplasmy mean in KSS?
Heteroplasmy is the mix of healthy and damaged mitochondria within a single cell or tissue. The ratio of healthy to damaged mitochondria determines how severely a specific organ or body part will be affected by the disease.
Is Kearns-Sayre Syndrome related to other genetic diseases?
Yes, KSS is part of a spectrum called Single Large-Scale mtDNA Deletion Syndromes (SLSMDS). This spectrum also includes Pearson Syndrome, which affects infants, and Chronic Progressive External Ophthalmoplegia (CPEO), which is often a milder form affecting mainly the eyes.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was the heteroplasmy level in the tissue that was tested (muscle or blood)?
  2. 2.How large is the deletion in my mitochondrial DNA, and does its size typically correlate with specific symptoms?
  3. 3.Since KSS is part of a spectrum, should we look back at my childhood health records for signs of Pearson syndrome, like early anemia?
  4. 4.Are there specific activities or stressors (like illness or fasting) that could put more strain on my mitochondria?

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 (19)
  1. 1

    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
  2. 2

    Molecular Aspects of Mitochondrial Dysfunction in Diabetes, Pearson and Kearns-Sayre Syndromes, and Neurodegenerative Disorders.

    Shafiee A, Akhlaghi AA, Ellstrom A, et al.

    International journal of general medicine 2025; (18()):5355-5366 doi:10.2147/IJGM.S539967.

    PMID: 40959587
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    Mitochondrial disorders: Understanding mitochondrial DNA point mutations and deletion syndromes.

    Heuer B, Seibert DC

    Journal of the American Association of Nurse Practitioners 2022; (34(8)):954-956 doi:10.1097/JXX.0000000000000755.

    PMID: 36330549
  4. 4

    Kearns-Sayre syndrome with a novel large-scale deletion: a case report.

    Zhu Q, Chen C, Yao J

    BMC ophthalmology 2022; (22(1)):35 doi:10.1186/s12886-021-02224-7.

    PMID: 35073857
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    Response to Growth hormone deficiency in mitochondrial disorders.

    Quintos JB, Hodax JK, Gonzales-Ellis BA, et al.

    Journal of pediatric endocrinology & metabolism : JPEM 2017; (30(4)):483-484.

    PMID: 28315851
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    Analysis of Mutational Burden of Mitochondrial Genome in Cells of Different Human Organs and Tissues.

    Sazonova MA, Sinyov VV, Ryzhkova AI, et al.

    Current medicinal chemistry 2025; (32(15)):3028-3043 doi:10.2174/0109298673296881240816065357.

    PMID: 39185646
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    Detecting mitochondrial electron transport chain enzyme defects in low-heteroplasmy single large-scale mtDNA deletion syndromes (SLSMDSs).

    Pan X, Wang Y, Liu N, et al.

    Molecular genetics and metabolism 2025; (146(3)):109260 doi:10.1016/j.ymgme.2025.109260.

    PMID: 41086592
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    PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome.

    Ahier A, Dai CY, Kirmes I, et al.

    Cell reports 2021; (35(9)):109203 doi:10.1016/j.celrep.2021.109203.

    PMID: 34077728
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    Clinical and Brain Magnetic Resonance Imaging Features in a Cohort of Chinese Patients with Kearns-Sayre Syndrome.

    Yu M, Zhang Z, Wang QQ, et al.

    Chinese medical journal 2016; (129(12)):1419-24 doi:10.4103/0366-6999.183417.

    PMID: 27270536
  10. 10

    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
  11. 11

    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
  12. 12

    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
  13. 13

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

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

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

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    Recognizing the evolution of clinical syndrome spectrum progression in individuals with single large-scale mitochondrial DNA deletion syndromes (SLSMDS).

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    Broadening the phenotypic spectrum of Pearson syndrome: Five new cases and a review of the literature.

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    American journal of medical genetics. Part A 2020; (182(2)):365-373 doi:10.1002/ajmg.a.61433.

    PMID: 31825167
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    The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions.

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    Brain sciences 2020; (10(11)) doi:10.3390/brainsci10110766.

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    Pearson syndrome.

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    Successful cord blood transplantation for del7q myelodysplastic syndrome in Pearson marrow pancreas syndrome.

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    PMID: 37732815

This information is for educational purposes to help you understand the biology of Kearns-Sayre Syndrome and does not replace professional medical advice. Always consult your healthcare provider or genetic counselor for specific medical guidance.

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