Kearns-Sayre syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: KSS
Oculocraniosomatic syndrome
Ophthalmoplegia-plus syndrome
CPEO with ragged-red fibers
CPEO with myopathy
Chronic progressive external ophthalmoplegia with myopathy
Ophthalmoplegia, progressive external, with ragged-red fibers
Mitochondrial cytopathy
Ophthalmoplegia, pigmentary degeneration of retina, and cardiomyopathy
Number of Symptoms 61
OrphanetNr: 480
OMIM Id: 530000
ICD-10: H49.8
UMLs: C0022541
MeSH: D007625
MedDRA: 10048804
Snomed: 25792000
51464001
77835008

Prevalence, inheritance and age of onset:

Prevalence: <= 9 of 100 000
Inheritance: Mitochondrial
25540845 [IBIS]
Age of onset: Childhood
Adolescent
Adult
25540845 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disease with dilated cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Mitochondrial disease with epilepsy
 -Rare neurologic disease
Mitochondrial disease with eye involvement
 -Rare eye disease
 -Rare genetic disease
Mitochondrial disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease
Mitochondrial myopathy
 -Rare genetic disease
 -Rare neurologic disease
Mitochondrial oxidative phosphorylation disorder due to a large-scale single deletion of mitochondrial DNA
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Syndrome with a symptomatic strabismus
 -Rare eye disease
 -Rare genetic disease
Syndrome with hypoparathyroidism
 -Rare endocrine disease
 -Rare genetic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease
Syndromic retinitis pigmentosa
 -Rare eye disease
 -Rare genetic disease

Comment:

Kearns-Sayre syndrome (KSS) is caused by various mitochondrial deletions [OMIM#530000]. This mitochondrial disorder is characterised by onset before the age of 20 years, progressive external ophthalmoplegia, and pigmentary retinopathy, accompanied by either cardiac conduction defects, elevated cerebrospinal fluid protein or cerebellar ataxia. 50% of patients with KSS develop cardiac complications. 1/3 of KSS patients have a 4.9 kb deletion of mtDNA from position 8469 to 13,447 (PMID:25540845). MERRF and Kearns-Sayre overlap syndrome due to the mtDNA m.3291T>C mutation (PMID:21996807). Involved genes: MT-TL1 (PMID:21996807); MT-ATP8 (Orphanet); RRM2B (Orphanet);

Symptom Information: Sort by abundance 

1
 (HPO:0001994) Renal Fanconi syndrome 22875312 IBIS 12 / 7739
2
 (HPO:0001947) Renal tubular acidosis 2234434 IBIS 21 / 7739
3
 (HPO:0007703) Abnormality of retinal pigmentation Very frequent [IBIS] Very frequent [Orphanet] 3192850 IBIS 21 / 7739
4
 (HPO:0000602) Ophthalmoplegia Very frequent [IBIS] Very frequent [Orphanet] hallmark [HPO] 25540845 IBIS 56 / 7739
5
 (HPO:0000580) Pigmentary retinopathy 25540845 IBIS 49 / 7739
6
 (HPO:0000597) Ophthalmoparesis Very frequent [Orphanet] 25368789 IBIS 71 / 7739
7
 (HPO:0000590) Progressive external ophthalmoplegia 25540845 IBIS 23 / 7739
8
 (HPO:0001488) Bilateral ptosis 25540845 IBIS 42 / 7739
9
 (HPO:0000510) Rod-cone dystrophy Very frequent [Orphanet] 25540845 IBIS 266 / 7739
10
 (HPO:0000508) Ptosis 25540845 IBIS 459 / 7739
11
 (HPO:0000544) External ophthalmoplegia Very frequent [Orphanet] hallmark [HPO] 25540845 IBIS 40 / 7739
12
 (HPO:0000365) Hearing impairment Frequent [Orphanet] 11422310 IBIS 539 / 7739
13
 (HPO:0000407) Sensorineural hearing impairment 22875312 IBIS 524 / 7739
14
 (HPO:0002321) Vertigo Frequent [Orphanet] 8151637 IBIS 58 / 7739
15
 (HPO:0001265) Hyporeflexia Frequent [Orphanet] typical [HPO] 9435373 IBIS 208 / 7739
16
 (HPO:0001250) Seizures 9404143 IBIS 1245 / 7739
17
 (HPO:0002141) Gait imbalance Frequent [Orphanet] 3179091 IBIS 55 / 7739
18
 (HPO:0002311) Incoordination Frequent [Orphanet] 12640554 IBIS 84 / 7739
19
 (HPO:0001251) Ataxia Frequent [Orphanet] typical [HPO] 25540845 IBIS 413 / 7739
20
 (HPO:0004374) Hemiplegia/hemiparesis Occasional [Orphanet] 9404143 IBIS 158 / 7739
21
 (HPO:0000726) Dementia 25540845 IBIS 131 / 7739
22
 (HPO:0002922) Increased CSF protein 22875312 IBIS 27 / 7739
23
 (HPO:0000763) Sensory neuropathy 25540845 IBIS 78 / 7739
24
 (HPO:0001315) Reduced tendon reflexes Frequent [Orphanet] 22875312 IBIS 160 / 7739
25
 (HPO:0000859) Hyperaldosteronism 1424198 IBIS 17 / 7739
26
 (HPO:0011735) Adrenocorticotropin deficient adrenal insufficiency 9701704 IBIS 3 / 7739
27
 (HPO:0008207) Primary adrenal insufficiency 22875312 IBIS 26 / 7739
28
 (HPO:0000846) Adrenal insufficiency 25061332 IBIS 24 / 7739
29
 (HPO:0000829) Hypoparathyroidism 1424198 IBIS 22 / 7739
30
 (HPO:0000819) Diabetes mellitus 11422310 IBIS 131 / 7739
31
 (HPO:0000830) Anterior hypopituitarism Frequent [Orphanet] 22284844 IBIS 9 / 7739
32
 (HPO:0002135) Basal ganglia calcification 1424198 IBIS 37 / 7739
33
 (HPO:0001738) Exocrine pancreatic insufficiency 23549648 IBIS 23 / 7739
34
 (HPO:0004322) Short stature Frequent [Orphanet] 25540845 IBIS 1232 / 7739
35
 (HPO:0011675) Arrhythmia Very frequent [Orphanet] 25540845 IBIS 226 / 7739
36
 (HPO:0011706) Second degree atrioventricular block 25061332 IBIS 2 / 7739
37
 (HPO:0011705) First degree atrioventricular block 25061332 IBIS 13 / 7739
38
 (HPO:0004308) Ventricular arrhythmia 25540845 IBIS 46 / 7739
39
 (HPO:0001638) Cardiomyopathy Very frequent [IBIS] 25540845 IBIS 192 / 7739
40
 (HPO:0001709) Third degree atrioventricular block 25061332 IBIS 3 / 7739
41
 (HPO:0011710) Bundle branch block Very frequent [Orphanet] 25061332 IBIS 14 / 7739
42
 (HPO:0001678) Atrioventricular block Very frequent [Orphanet] hallmark [HPO] 25061332 IBIS 59 / 7739
43
 (HPO:0001924) Sideroblastic anemia 1407387 IBIS 12 / 7739
44
 (HPO:0003236) Elevated serum creatine phosphokinase Frequent [Orphanet] 21996807 IBIS 214 / 7739
45
 (HPO:0002917) Hypomagnesemia 1424198 IBIS 19 / 7739
46
 (HPO:0003128) Lactic acidosis 25540845 IBIS 116 / 7739
47
 (HPO:0001611) Nasal speech 23549648 IBIS 48 / 7739
48
 (HPO:0001324) Muscle weakness Frequent [Orphanet] typical [HPO] 25540845 IBIS 859 / 7739
49
 (HPO:0003457) EMG abnormality Frequent [Orphanet] 22875312 IBIS 78 / 7739
50
 (HPO:0003200) Ragged-red muscle fibers Very frequent [IBIS] 25061332 IBIS 37 / 7739
51
 (HPO:0003560) Muscular dystrophy Frequent [Orphanet] 1755871 IBIS 88 / 7739
52
 (HPO:0100295) Muscle fiber atrophy Frequent [Orphanet] typical [HPO] 1934767 IBIS 22 / 7739
53
 (HPO:0001252) Muscular hypotonia Frequent [Orphanet] 1305030 IBIS 990 / 7739
54
 (OMIM) Decreased serum and muscle coenzyme Q 25061332 IBIS 1 / 7739
55
 (MedDRA:10051403) Mitochondrial DNA deletion 25061332 IBIS 6 / 7739
56
 (OMIM) Bulbar dysfunction 23549648 IBIS 4 / 7739
57
 (OMIM) Diffuse signal abnormality of central white matter 8151637 IBIS 1 / 7739
58
 (MedDRA:10049447) Tachyarrhythmia 25540845 IBIS 1 / 7739
59
 (MedDRA:10000032) Cardiac conduction disorders 23549648 IBIS 5 / 7739
60
 (OMIM) Decreased cerebrospinal fluid folic acid 20388557 IBIS 1 / 7739
61
 (MedDRA:10016219) Fanconi syndrome 22875312 IBIS 3 / 7739

Associated genes:

MT-TL1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
MT-TL1 rs199474667 pathogenic RCV000010222.3
MT-TY rs118203893 pathogenic RCV000010161.4
MT-TY rs606231176 pathogenic RCV000010160.4

Additional Information: