Kearns-Sayre syndrome is a single large-scale mitochondrial DNA deletion syndrome with onset before age 20 years. The primary lesion is a heteroplasmic mtDNA deletion in post-mitotic tissues, especially skeletal and extraocular muscle, retina, cardiac conduction tissue, and central nervous system. The deletion compromises mitochondrial translation and respiratory-chain oxidative phosphorylation, producing chronic progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction disease, with frequent ataxia, hearing impairment, endocrine disease, and lactic-acid biochemical stress. It is modeled as a distinct disorder entry rather than a subtype of Pearson syndrome because it has its own MONDO/OMIM/Orphanet identity and a different tissue-dominant clinical mechanism; both entries are grouped under single large-scale mtDNA deletion disorders.
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name: Kearns-Sayre syndrome
creation_date: "2026-07-06T01:07:38Z"
category: Mendelian
synonyms:
- KSS
- Kearns Sayre Syndrome
description: >-
Kearns-Sayre syndrome is a single large-scale mitochondrial DNA deletion
syndrome with onset before age 20 years. The primary lesion is a heteroplasmic
mtDNA deletion in post-mitotic tissues, especially skeletal and extraocular
muscle, retina, cardiac conduction tissue, and central nervous system. The
deletion compromises mitochondrial translation and respiratory-chain oxidative
phosphorylation, producing chronic progressive external ophthalmoplegia,
pigmentary retinopathy, and cardiac conduction disease, with frequent ataxia,
hearing impairment, endocrine disease, and lactic-acid biochemical stress.
It is modeled as a distinct disorder entry rather than a subtype of Pearson
syndrome because it has its own MONDO/OMIM/Orphanet identity and a different
tissue-dominant clinical mechanism; both entries are grouped under single
large-scale mtDNA deletion disorders.
references:
- reference: PMID:20301382
title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
tags:
- GeneReviews
- reference: PMID:3412580
title: Deletions of mitochondrial DNA in Kearns-Sayre syndrome.
- reference: PMID:25352051
title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
disease_term:
preferred_term: Kearns-Sayre syndrome
term:
id: MONDO:0010787
label: Kearns-Sayre syndrome
parents:
- mitochondrial disease
- progressive external ophthalmoplegia
mappings:
mondo_mappings:
- term:
id: MONDO:0010787
label: Kearns-Sayre syndrome
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this Kearns-Sayre syndrome entry.
external_assertions:
- name: OMIM Kearns-Sayre syndrome record
source: OMIM
assertion_type: disease_record
external_id: OMIM:530000
url: https://omim.org/entry/530000
description: OMIM phenotype record for Kearns-Sayre syndrome.
- name: Orphanet Kearns-Sayre syndrome record
source: Orphanet
assertion_type: structured_disease_record
external_id: ORPHA:480
url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=480
description: Orphanet structured disease record for Kearns-Sayre syndrome.
classifications:
icimd_category:
- classification_value: single_large_scale_mtdna_deletions
notes: >-
WP-015 seed 6.3.02.01. Kearns-Sayre syndrome is one of the ICIMD disorders
associated with single large-scale mtDNA deletions.
inheritance:
- name: Usually de novo mitochondrial inheritance
description: >-
Kearns-Sayre syndrome is part of the single large-scale mitochondrial DNA
deletion syndrome spectrum. Most cases are de novo, with rare maternal
transmission possible when an affected mother carries a mtDNA deletion.
inheritance_term:
preferred_term: Mitochondrial inheritance
term:
id: HP:0001427
label: Mitochondrial inheritance
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
SLSMDSs are almost never inherited, suggesting that these disorders are
typically caused by a de novo single large-scale mitochondrial DNA
explanation: GeneReviews describes the SLSMD inheritance pattern as usually de novo.
pathophysiology:
- name: Single Large-Scale mtDNA Deletion in Post-Mitotic Tissues
description: >-
Kearns-Sayre syndrome is caused by a single large-scale deletion of
mitochondrial DNA, usually sporadic and heteroplasmic. Deleted genomes are
detected in affected tissues such as skeletal muscle; the proportion of
deleted mtDNA, rather than a nuclear-gene defect, determines whether
high-energy post-mitotic tissues cross the bioenergetic threshold.
role: trigger
biological_processes:
- preferred_term: mitochondrial DNA metabolic process
term:
id: GO:0032042
label: mitochondrial DNA metabolic process
modifier: ABNORMAL
evidence:
- reference: PMID:3412580
reference_title: Deletions of mitochondrial DNA in Kearns-Sayre syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: seven of seven patients with Kearns-Sayre syndrome (KSS).
explanation: The foundational KSS study identified mtDNA deletions in all seven tested patients.
- reference: PMID:3412580
reference_title: Deletions of mitochondrial DNA in Kearns-Sayre syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The deletions ranged in size from 2.0 to 7.0 kb
explanation: This supports the large-scale variable-size deletion mechanism in KSS.
downstream:
- target: Mitochondrial Translation and OXPHOS Deficiency
causal_link_type: DIRECT
description: >-
Deletion of mtDNA sequence reduces the mitochondrial gene products needed
for respiratory-chain oxidative phosphorylation.
- name: Mitochondrial Translation and OXPHOS Deficiency
conforms_to: "mitochondrial_dysfunction#Bioenergetic Decline and Oxidative Stress"
description: >-
The deleted mtDNA population reduces mitochondrial translation capacity and
oxidative phosphorylation. The pathway product state is impaired ATP
generation with lactate accumulation during cellular stress; clinical
expression is strongest in extraocular muscle, retina, cardiac conduction
tissue, and central nervous system.
role: central_effector
biological_processes:
- preferred_term: mitochondrial translation
term:
id: GO:0032543
label: mitochondrial translation
modifier: DECREASED
- preferred_term: oxidative phosphorylation
term:
id: GO:0006119
label: oxidative phosphorylation
modifier: DECREASED
- preferred_term: aerobic respiration
term:
id: GO:0009060
label: aerobic respiration
modifier: DECREASED
chemical_entities:
- preferred_term: ATP
term:
id: CHEBI:15422
label: ATP
modifier: DECREASED
- preferred_term: (S)-lactate
term:
id: CHEBI:16651
label: (S)-lactate
modifier: INCREASED
evidence:
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Blood lactate was raised (>2.0
explanation: This pediatric SLSMD cohort supports lactate elevation as a biochemical readout of respiratory-chain energy failure.
downstream:
- target: Ocular and Retinal Energy Failure
causal_link_type: DIRECT
description: >-
Energy failure in extraocular muscle and retina produces CPEO/ptosis and
pigmentary retinopathy.
- target: Cardiac Conduction and Neurologic Energy Failure
causal_link_type: DIRECT
description: >-
Energy failure in conduction tissue and neural structures produces heart
block, ataxia, hearing impairment, and other multisystem KSS features.
- name: Ocular and Retinal Energy Failure
description: >-
Extraocular muscle involvement produces ptosis and chronic progressive
external ophthalmoplegia, while retinal energy failure produces pigmentary
retinopathy. These findings define the core Kearns-Sayre phenotype.
role: consequence
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: retinopathy, CPEO, and cardiac conduction abnormality.
explanation: GeneReviews names pigmentary retinopathy and CPEO as cardinal KSS features.
- reference: PMID:21165624
reference_title: "[Kearns-Sayre syndrome : a mitochondrial disease (OMIM #530000)]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: progressive external ophthalmoplegia, atypical retinitis pigmentosa and cardiac
explanation: The clinical report summarizes the KSS triad, including PEO and retinal disease.
downstream:
- target: Progressive external ophthalmoplegia
causal_link_type: DIRECT
- target: Ptosis
causal_link_type: DIRECT
- target: Pigmentary retinopathy
causal_link_type: DIRECT
- name: Cardiac Conduction and Neurologic Energy Failure
description: >-
KSS energy failure extends to cardiac conduction tissue and central/auditory
pathways. Conduction block can be life-threatening; neurologic involvement
includes cerebellar ataxia, sensorineural hearing impairment, basal ganglia
or white-matter lesions, and cognitive or endocrine complications in some
patients.
role: consequence
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: Additional features can include cerebellar ataxia, tremor, intellectual disability or cognitive decline,
explanation: GeneReviews supports neurologic involvement beyond the cardinal ocular-retinal-cardiac triad.
- reference: PMID:21165624
reference_title: "[Kearns-Sayre syndrome : a mitochondrial disease (OMIM #530000)]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: life-threatening complications which can lead to sudden cardiac death.
explanation: This supports the clinical importance of cardiac conduction disease in KSS.
downstream:
- target: Heart block
causal_link_type: DIRECT
- target: Ataxia
causal_link_type: DIRECT
- target: Sensorineural hearing impairment
causal_link_type: DIRECT
phenotypes:
- name: Progressive external ophthalmoplegia
category: Ophthalmologic
description: Chronic progressive external ophthalmoplegia is a defining KSS feature.
phenotype_term:
preferred_term: Progressive external ophthalmoplegia
term:
id: HP:0000590
label: Progressive external ophthalmoplegia
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: retinopathy, CPEO, and cardiac conduction abnormality.
explanation: GeneReviews includes CPEO in the defining KSS feature set.
- name: Ptosis
category: Ophthalmologic
description: Ptosis can precede full ophthalmoplegia in childhood SLSMD presentations.
phenotype_term:
preferred_term: Ptosis
term:
id: HP:0000508
label: Ptosis
evidence:
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The most frequent neurological manifestation was ptosis, affecting 22 patients
explanation: The pediatric SLSMD cohort documents ptosis as the most frequent neurologic manifestation.
- name: Pigmentary retinopathy
category: Ophthalmologic
description: Pigmentary retinal degeneration is part of the KSS diagnostic triad.
phenotype_term:
preferred_term: Pigmentary retinopathy
term:
id: HP:0000580
label: Pigmentary retinopathy
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: retinopathy, CPEO, and cardiac conduction abnormality.
explanation: GeneReviews includes pigmentary retinopathy in the defining KSS feature set.
- name: Heart block
category: Cardiovascular
description: Cardiac conduction disease can progress to complete heart block and sudden death risk.
phenotype_term:
preferred_term: Heart block
term:
id: HP:0012722
label: Heart block
evidence:
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: complete heart block in five
explanation: The pediatric SLSMD cohort documents complete heart block in affected children.
- name: Ataxia
category: Neurologic
description: Cerebellar ataxia is a recognized additional KSS feature.
phenotype_term:
preferred_term: Ataxia
term:
id: HP:0001251
label: Ataxia
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: Additional features can include cerebellar ataxia, tremor, intellectual disability or cognitive decline,
explanation: GeneReviews lists cerebellar ataxia among additional KSS features.
- name: Sensorineural hearing impairment
category: Otolaryngologic
description: Sensorineural hearing impairment is common in the KSS/SLSMD spectrum.
phenotype_term:
preferred_term: Sensorineural hearing impairment
term:
id: HP:0000407
label: Sensorineural hearing impairment
evidence:
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Ten of 15 patients tested had sensorineural hearing loss
explanation: The pediatric SLSMD cohort documents sensorineural hearing loss in tested patients.
biochemical:
- name: Elevated lactate
presence: INCREASED
biomarker_term:
preferred_term: (S)-lactate
term:
id: CHEBI:16651
label: (S)-lactate
evidence:
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Blood lactate was raised (>2.0
explanation: The pediatric SLSMD cohort supports elevated blood lactate as a biochemical readout.
diagnosis:
- name: Mitochondrial DNA deletion testing
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
description: >-
Molecular testing identifies a single large-scale mtDNA deletion. In
children, blood or urine testing can often detect the deletion; adult cases
may require skeletal muscle.
results: Detection of a single large-scale mtDNA deletion supports Kearns-Sayre syndrome in the correct clinical setting.
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: (mtDNA) deletion ranging in size from 1.1 to 10 kb on molecular genetic testing.
explanation: GeneReviews defines molecular testing for single large-scale mtDNA deletion syndromes.
treatments:
- name: Multidisciplinary surveillance and supportive care
description: >-
Management is supportive and surveillance-focused, including cardiac
conduction monitoring with pacing when indicated, neurologic and
ophthalmologic care, hearing support, endocrine surveillance, nutrition and
rehabilitation support, and avoidance of individualized mitochondrial-toxic
medication risks.
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: cardiac pacemaker in individuals with cardiac conduction block, with
explanation: GeneReviews supports pacemaker consideration for KSS/SLSMD cardiac conduction block.
- reference: PMID:25352051
reference_title: "Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: need for coordinated care of children with SLSMDs at a tertiary specialist centre.
explanation: The pediatric cohort supports coordinated multispecialty care for SLSMDs.
notes: >-
Scope decision: Kearns-Sayre syndrome is kept as a separate Disease entry
because it has a distinct MONDO identity (MONDO:0010787; OMIM:530000;
ORPHA:480) and a post-mitotic ocular-retinal-cardiac mechanism distinct from
the infantile marrow-pancreas presentation of Pearson syndrome. The shared
SLSMD mechanism is captured in the Single Large-Scale mtDNA Deletion Disorders
grouping.