CAPOS
MCID: CRB189
MIFTS: 36

Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss (CAPOS)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

MalaCards integrated aliases for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

Name: Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss 57 72
Capos Syndrome 57 20 58 72 36 39 70
Cerebellar Ataxia-Areflexia-Pes Cavus-Optic Atrophy-Sensorineural Hearing Loss Syndrome 20 58 29 6
Capos 57 20 72
Cerebellar Ataxia - Areflexia - Pes Cavus - Optic Atrophy - Sensorineural Hearing Loss 20
Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy and Sensorinural Hearing Loss 20
Cerebellar Ataxia-Areflexia-Pes Cavus-Optic Atrophy-Sensorineural Deafness Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
Inheritance: Autosomal dominant,Mitochondrial inheritance; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood
recurrent acute episodes of neurologic deterioration associated with febrile illnesses
acute episodes decrease with age and disappear
residual neurologic deficits are slowly progressive
visual and hearing loss are slowly progressive
four unrelated families of caucasian european descent have been reported (last curated february 2015)


HPO:

31
cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare otorhinolaryngological diseases
Developmental anomalies during embryogenesis


Summaries for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

GARD : 20 Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome is a neurological disorder. The syndrome gets its name from the different parts of the body it usually affects: Cerebellar ataxia : inflammation of the cerebellum, the part of the brain that helps control the coordination of muscle movement Areflexia: loss of reflexes Pes cavus : high arch in foot Optic atrophy : damage to the optic nerve of the eye Sensorinural hearing loss : damage to the nerves involved in hearing CAPOS syndrome typically begins after a fever-related illness with a sudden episode of ataxia, such as having a hard time walking or coordinating leg or arm movements. The ataxia is usually associated with generalized weakness and/or inflammation of the brain ( encephalopathy ). The first episode most often happens between the ages of 6 months and 5 years. Pregnancy and delivery may also trigger episodes. Most people with CAPOS syndrome have one to three episodes during their lifetime. Other signs and symptoms during an episode may include low muscle tone, unusual eye movements ( nystagmus or strabismus ), problems with speech ( dysarthria ), difficulty swallowing ( dysphagia ), reduced or absent reflexes, and hearing loss. Some people may lose consciousness or go into a coma during an episode. Though many of the signs and symptoms of CAPOS syndrome get better as the fever and illness improve, some symptoms, including movement problems, may continue. Vision changes ( optic atrophy ) and sensorineural hearing loss tend to worsen over time, although the severity and rate of progression varies. Long-term management may include physical therapy, hearing and vision aids, and regular exams to check for changes in vision, hearing, and muscle coordination.

MalaCards based summary : Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss, also known as capos syndrome, is related to 3-methylglutaconic aciduria, type iii and ataxia and polyneuropathy, adult-onset, and has symptoms including gait ataxia, hemiparesis and cerebellar ataxia. An important gene associated with Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss is ATP1A3 (ATPase Na+/K+ Transporting Subunit Alpha 3). Affiliated tissues include eye, cerebellum and heart, and related phenotypes are ataxia and muscle weakness

OMIM® : 57 Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) is an autosomal dominant neurologic disorder characterized by early-childhood onset of recurrent episodes of acute ataxic encephalopathy associated with febrile illnesses. These acute episodes tend to decrease with time, but the neurologic sequelae are permanent and progressive, resulting in gait and limb ataxia and areflexia. Affected individuals also develop progressive visual impairment due to optic atrophy and sensorineural hearing loss beginning in childhood. More variable features include abnormal eye movements, pes cavus, and dysphagia (summary by Demos et al., 2014). (601338) (Updated 20-May-2021)

KEGG : 36 Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome is a rare autosomal dominant neurological disorder. CAPOS is characterized by a relapsing, early onset cerebellar ataxia, associated with progressive optic atrophy and sensorineural deafness. An identical heterozygous missense mutation in ATP1A3 gene was found in CAPOS patients.

UniProtKB/Swiss-Prot : 72 Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss: An autosomal dominant neurologic disorder characterized by relapsing and partially remitting, early-onset cerebellar ataxia following a febrile illness. Other features include progressive optic atrophy and sensorineural hearing loss, generalized hypotonia, areflexia and pes cavus without evidence of a peripheral neuropathy on neurophysiological studies.

Related Diseases for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Graphical network of the top 20 diseases related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:



Diseases related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss

Symptoms & Phenotypes for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Human phenotypes related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001324
3 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
4 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
5 areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001284
6 encephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001298
7 abnormality of eye movement 58 31 occasional (7.5%) Occasional (29-5%) HP:0000496
8 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
9 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
10 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
11 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
12 autistic behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000729
13 seizure 31 occasional (7.5%) HP:0001250
14 seizures 58 Occasional (29-5%)
15 nystagmus 31 HP:0000639
16 dysarthria 31 HP:0001260
17 blindness 31 HP:0000618
18 progressive visual loss 31 HP:0000529
19 dysmetria 31 HP:0001310
20 gait ataxia 31 HP:0002066
21 hemiparesis 31 HP:0001269
22 episodic ataxia 31 HP:0002131
23 progressive sensorineural hearing impairment 31 HP:0000408
24 truncal ataxia 31 HP:0002078
25 incoordination 31 HP:0002311
26 episodic generalized hypotonia 31 HP:0006852

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
nystagmus
optic atrophy
blindness
visual loss, progressive
eye movement abnormalities

Neurologic Peripheral Nervous System:
areflexia

Muscle Soft Tissue:
hypotonia
weakness, episodic

Neurologic Behavioral Psychiatric Manifestations:
autistic features (1 family)

Neurologic Central Nervous System:
dysarthria
dysmetria
dystonia
gait ataxia
hemiparesis
more
Skeletal Feet:
pes cavus

Head And Neck Ears:
sensorineural hearing loss, progressive

Clinical features from OMIM®:

601338 (Updated 20-May-2021)

UMLS symptoms related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:


gait ataxia; hemiparesis; cerebellar ataxia; reflex, abnormal; ataxia, truncal

Drugs & Therapeutics for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 CAPO: Continuous Glucose Monitoring in A2 Gestational Diabetes and Pregnancy Outcomes Recruiting NCT04219085

Search NIH Clinical Center for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss

Genetic Tests for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Genetic tests related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

# Genetic test Affiliating Genes
1 Cerebellar Ataxia-Areflexia-Pes Cavus-Optic Atrophy-Sensorineural Hearing Loss Syndrome 29 ATP1A3

Anatomical Context for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

MalaCards organs/tissues related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

40
Eye, Cerebellum, Heart

Publications for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Articles related to Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

(show all 43)
# Title Authors PMID Year
1
Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome. 57 6 61
25056583 2014
2
A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. 57 6 61
24468074 2014
3
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. 61 57 6
8733056 1996
4
Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study. 57 61
32913013 2020
5
The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management. 6 61
29305691 2018
6
De novo p.Arg756Cys mutation of ATP1A3 causes an atypical form of alternating hemiplegia of childhood with prolonged paralysis and choreoathetosis. 61 6
27634470 2016
7
Novel pregnancy-triggered episodes of CAPOS syndrome. 20 61
29090527 2018
8
Early Diagnosis of CAPOS Syndrome Before Acute-Onset Ataxia-Review of the Literature and a New Family. 20 61
28483396 2017
9
Mosaicism in ATP1A3-related disorders: not just a theoretical risk. 6
27726050 2017
10
Childhood-onset ATP1A3-related conditions: Report of two new cases of phenotypic spectrum. 6
27268479 2016
11
Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. 6
26400718 2015
12
Cochlear Implantation Outcomes in Post Synaptic Auditory Neuropathies: A Systematic Review and Narrative Synthesis. 61
33136025 2020
13
Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity. 61
32653672 2020
14
ATP1A3 mutation presenting as CAPOS syndrome + dystonia phenotype. 61
32576493 2020
15
CAPOS Syndrome: A Rare ATP1A3-Related Disorder. 61
32606553 2020
16
[A novel variation in ATP1A3 gene in a child with CAPOS syndrome]. 61
32135597 2020
17
ATP1A3-related epilepsy: Report of seven cases and literature-based analysis of treatment response. 61
31959558 2020
18
Clinical and Genetic Spectrum of ATP1A3-Related Disorders in a Korean Pediatric Population. 61
31942761 2020
19
Chronological dynamic changes in cortico-subcortical imbalance of cerebral blood flow in a boy with CAPOS syndrome. 61
30904181 2019
20
Findings from aetiological investigation of Auditory Neuropathy Spectrum Disorder in children referred to cochlear implant programs. 61
30554714 2019
21
Fever-related ataxia: a case report of CAPOS syndrome. 61
31410291 2019
22
Functional consequences of the CAPOS mutation E818K of Na+,K+-ATPase. 61
30409907 2019
23
Cochlear Implantation in a Case of Auditory Neuropathy Spectrum Disorder with CAPOS Syndrome. 61
32821455 2019
24
Early Life Epilepsy and Episodic Apnea Revealing an ATP1A3 Mutation: Report of a Pediatric Case and Literature Review. 61
30011403 2018
25
Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity. 61
29801192 2018
26
De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome. 61
29922587 2018
27
Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report. 61
29625811 2018
28
Childhood Rapid-Onset Ataxia: Expanding the Phenotypic Spectrum of ATP1A3 Mutations. 61
29397530 2018
29
ATP1A3 spectrum disorders: A video-documented history of 7 genetically confirmed early onset cases. 61
29396171 2018
30
ATP1A3-related disorders: An update. 61
29291920 2018
31
Childhood hearing loss is a key feature of CAPOS syndrome: A case report. 61
29287866 2018
32
ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy. 61
29184165 2017
33
Beyond Dystonia-Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations. 61
30363590 2016
34
The Genetic Homogeneity of CAPOS Syndrome: Four New Patients With the c.2452G>A (p.Glu818Lys) Mutation in the ATP1A3 Gene. 61
27091223 2016
35
Deficits in social behavioral tests in a mouse model of alternating hemiplegia of childhood. 61
27276195 2016
36
Insights into the Pathology of the α3 Na(+)/K(+)-ATPase Ion Pump in Neurological Disorders; Lessons from Animal Models. 61
27378932 2016
37
The Influence of Na(+), K(+)-ATPase on Glutamate Signaling in Neurodegenerative Diseases and Senescence. 61
27313535 2016
38
CAPOS syndrome and hemiplegic migraine in a novel pedigree with the specific ATP1A3 mutation. 61
26453127 2015
39
Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome. 61
25809299 2015
40
Genome sequencing identifies a novel mutation in ATP1A3 in a family with dystonia in females only. 61
25359261 2015
41
Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations. 61
26417536 2015
42
The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. 61
25447930 2015
43
ATP1A3-Related Neurologic Disorders 61
20301294 2008

Variations for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

ClinVar genetic disease variations for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ATP1A3 NM_152296.5(ATP1A3):c.2767G>A (p.Asp923Asn) SNV Pathogenic 12915 rs267606670 GRCh37: 19:42472989-42472989
GRCh38: 19:41968837-41968837
2 ATP1A3 NM_152296.5(ATP1A3):c.2312C>T (p.Thr771Ile) SNV Pathogenic 976730 GRCh37: 19:42474646-42474646
GRCh38: 19:41970494-41970494
3 ATP1A3 NM_152296.5(ATP1A3):c.2452G>A (p.Glu818Lys) SNV Pathogenic 156238 rs587777771 GRCh37: 19:42474427-42474427
GRCh38: 19:41970275-41970275
4 ATP1A3 NM_152296.5(ATP1A3):c.2401G>A (p.Asp801Asn) SNV Pathogenic 37107 GRCh37: 19:42474557-42474557
GRCh38: 19:41970405-41970405
5 ATP1A3 NM_152296.5(ATP1A3):c.2267G>A (p.Arg756His) SNV Pathogenic 161134 rs606231435 GRCh37: 19:42474691-42474691
GRCh38: 19:41970539-41970539
6 ATP1A3 NM_152296.5(ATP1A3):c.2443G>A (p.Glu815Lys) SNV Pathogenic 37108 rs387907281 GRCh37: 19:42474436-42474436
GRCh38: 19:41970284-41970284
7 ATP1A3 NM_152296.5(ATP1A3):c.2839G>A (p.Gly947Arg) SNV Pathogenic 37110 rs398122887 GRCh37: 19:42471896-42471896
GRCh38: 19:41967744-41967744
8 ATP1A3 NM_152296.5(ATP1A3):c.974G>A (p.Gly325Asp) SNV Likely pathogenic 216891 rs863224847 GRCh37: 19:42489089-42489089
GRCh38: 19:41984937-41984937
9 ATP1A3 NM_152296.5(ATP1A3):c.2224G>T (p.Asp742Tyr) SNV Likely pathogenic 431156 rs1135401822 GRCh37: 19:42479820-42479820
GRCh38: 19:41975668-41975668
10 ATP1A3 NM_152296.5(ATP1A3):c.460A>G (p.Met154Val) SNV Likely pathogenic 431154 rs1135401821 GRCh37: 19:42490279-42490279
GRCh38: 19:41986127-41986127
11 ATP1A3 NM_152296.5(ATP1A3):c.2266C>T (p.Arg756Cys) SNV Likely pathogenic 425189 rs1064797245 GRCh37: 19:42474692-42474692
GRCh38: 19:41970540-41970540
12 ATP1A3 NM_152296.5(ATP1A3):c.2543G>C (p.Gly848Ala) SNV Likely pathogenic 807377 rs1599705281 GRCh37: 19:42473732-42473732
GRCh38: 19:41969580-41969580
13 ATP1A3 NM_152296.5(ATP1A3):c.2839G>T (p.Gly947Trp) SNV Likely pathogenic 689735 rs398122887 GRCh37: 19:42471896-42471896
GRCh38: 19:41967744-41967744
14 ATP1A3 NM_152296.5(ATP1A3):c.1192+7G>A SNV Uncertain significance 625891 rs374826826 GRCh37: 19:42486053-42486053
GRCh38: 19:41981901-41981901
15 ATP1A3 NM_152296.5(ATP1A3):c.1176C>T (p.Thr392=) SNV Uncertain significance 625892 rs1353417724 GRCh37: 19:42486076-42486076
GRCh38: 19:41981924-41981924
16 ATP1A3 NM_152296.5(ATP1A3):c.1402G>T (p.Ala468Ser) SNV Uncertain significance 1031255 GRCh37: 19:42485689-42485689
GRCh38: 19:41981537-41981537

UniProtKB/Swiss-Prot genetic disease variations for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss:

72
# Symbol AA change Variation ID SNP ID
1 ATP1A3 p.Glu818Lys VAR_070772 rs587777771

Expression for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

Search GEO for disease gene expression data for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss.

Pathways for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

GO Terms for Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and...

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