CMTX4
MCID: CHR696
MIFTS: 32

Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia (CMTX4)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

Name: Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia 57 73
Cowchock Syndrome 57 58 73 36 29 13 6 39
Cmtx4 57 58 73
Charcot-Marie-Tooth Disease with Deafness and Mental Retardation 57 73
Cowck 57 73
Namsd 57 73
Nadmr 57 73
Neuropathy, Axonal Motor-Sensory, with Deafness and Mental Retardation; Namsd 57
Neuropathy, Axonal Motor-Sensory, with Deafness and Mental Retardation 57
Axonal Motor-Sensory Neuropathy with Deafness and Mental Retardation 73
Charcot-Marie-Tooth Disease Deafness Mental Retardation 74
Charcot-Marie-Tooth Disease X-Linked Recessive 4 73
X-Linked Charcot-Marie-Tooth Disease Type 4 58
Cowchock Syndrome; Cowck 57
Cmt4x 58

Characteristics:

Orphanet epidemiological data:

58
x-linked charcot-marie-tooth disease type 4
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
slowly progressive
variable age at onset (range infancy to young adult)
hearing loss is often presenting feature
highly variable features and severity

Inheritance:
x-linked recessive


HPO:

31
charcot-marie-tooth disease, x-linked recessive, 4, with or without cerebellar ataxia:
Inheritance x-linked recessive inheritance


Classifications:

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


External Ids:

OMIM® 57 310490
OMIM Phenotypic Series 57 PS118220
KEGG 36 H02344
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 72 C0795910
Orphanet 58 ORPHA101078
MedGen 41 C0795910

Summaries for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

OMIM® : 57 X-linked recessive Charcot-Marie-Tooth disease-4 with or without cerebellar ataxia (CMTX4) is a mitochondrial disorder manifest as progressive neurologic dysfunction with highly variable features. The age at onset ranges from infancy to young adulthood, and patients can present with different features, including hearing loss, delayed motor development, or difficulty walking due to peripheral neuropathy and/or cerebellar ataxia. Most patients develop all features, including a progressive sensorimotor axonal neuropathy and deafness due to auditory neuropathy. Additional more variable features can include cognitive impairment, cerebellar atrophy on brain imaging, cerebellar signs, such as dysarthria, abnormal extraocular movements, tremor, and dysmetria, as well as spasticity. There is significant intrafamilial variability: the variable features are consistent with mitochondrial dysfunction. Prolonged treatment with riboflavin may result in some mild improvement in the ataxia (summary by Rinaldi et al., 2012, Heimer et al., 2018, Bogdanova-Mihaylova et al., 2019). (310490) (Updated 05-Mar-2021)

MalaCards based summary : Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia, also known as cowchock syndrome, is related to charcot-marie-tooth disease x-linked recessive 4 and charcot-marie-tooth disease. An important gene associated with Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia is AIFM1 (Apoptosis Inducing Factor Mitochondria Associated 1), and among its related pathways/superpathways are Apoptosis and Necroptosis. Affiliated tissues include brain and skeletal muscle, and related phenotypes are sensorineural hearing impairment and cognitive impairment

KEGG : 36 Cowchock syndrome (CMTX4) is a slowly progressive X-linked recessive disorder with axonal neuropathy, deafness, and cognitive impairment. This syndrome is associated with a mutation in AIFM1, the gene encoding apoptosis-inducing factor.

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood.

Wikipedia : 74 Charcot-Marie-Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous... more...

Related Diseases for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:



Diseases related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Human phenotypes related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

31 58 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
2 cognitive impairment 31 occasional (7.5%) HP:0100543
3 intellectual disability 58 31 Frequent (79-30%) HP:0001249
4 hearing impairment 58 31 Frequent (79-30%) HP:0000365
5 sensory neuropathy 58 31 Very frequent (99-80%) HP:0000763
6 sleep disturbance 58 Occasional (29-5%)
7 scoliosis 58 Frequent (79-30%)
8 ataxia 58 Occasional (29-5%)
9 gait disturbance 58 Occasional (29-5%)
10 tremor 58 Occasional (29-5%)
11 kyphosis 58 Frequent (79-30%)
12 muscle weakness 31 HP:0001324
13 skeletal muscle atrophy 58 Very frequent (99-80%)
14 decreased nerve conduction velocity 58 Very frequent (99-80%)
15 elevated serum creatine kinase 31 HP:0003236
16 impaired pain sensation 58 Frequent (79-30%)
17 areflexia 58 Very frequent (99-80%)
18 pes cavus 58 Very frequent (99-80%)
19 distal muscle weakness 58 Very frequent (99-80%)
20 distal sensory impairment 31 HP:0002936
21 motor axonal neuropathy 31 HP:0007002
22 sensorimotor neuropathy 58 Very frequent (99-80%)
23 sensory axonal neuropathy 31 HP:0003390

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skeletal Feet:
pes cavus
hammertoes

Head And Neck Eyes:
optic atrophy (in some patients)
external ophthalmoplegia (in some patients)
retinopathy (in some patients)
abnormal smooth pursuit (in some patients)
abnormal saccades (in some patients)
more
Laboratory Abnormalities:
increased serum creatine kinase
increased serum transaminases

Head And Neck Ears:
hearing loss, sensorineural (in most patients)
auditory neuropathy (in most patients)
diminished abr (in most patients)

Neurologic Peripheral Nervous System:
hyporeflexia
axonal motor neuropathy (lower limbs more affected than upper limbs)
axonal sensory neuropathy (lower limbs more affected than upper limbs)
distal sensory impairment (lower limbs more affected than upper limbs)

Neurologic Central Nervous System:
cerebellar ataxia (in some patients)
spasticity (in some patients)
tremor (in some patients)
cognitive impairment (in some patients)
dysarthria (in some patients)
more
Muscle Soft Tissue:
neurogenic atrophy seen on muscle biopsy
distal muscle weakness due to peripheral neuropathy
distal muscle wasting due to peripheral neuropathy
increased numbers of abnormally-shaped mitochondria in subsarcolemmal areas
decreased complex iv activity (in some patients)

Clinical features from OMIM®:

310490 (Updated 05-Mar-2021)

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia

Genetic Tests for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Genetic tests related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

# Genetic test Affiliating Genes
1 Cowchock Syndrome 29 AIFM1

Anatomical Context for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

40
Brain, Skeletal Muscle

Publications for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Articles related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

# Title Authors PMID Year
1
Clinical spectrum of AIFM1-associated disease in an Irish family, from mild neuropathy to severe cerebellar ataxia with colour blindness. 6 57 61
31523922 2019
2
Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. 61 57 6
23217327 2012
3
Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin. 57 6
28967629 2018
4
A slowly progressive mitochondrial encephalomyopathy widens the spectrum of AIFM1 disorders. 6 57
25934856 2015
5
X-linked motor-sensory neuropathy type-II with deafness and mental retardation: a new disorder. 57 6
3856385 1985
6
A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq24-q26. 57
8666389 1995
7
X-linked neuropathy: gene localization with DNA probes. 57
3024556 1986
8
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017
9
A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease. 61
26173962 2016

Variations for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAB33A NM_004208.4(AIFM1):c.1478A>T (p.Glu493Val) SNV Pathogenic 39601 rs281864468 X:129265745-129265745 X:130131770-130131770
2 RAB33A NM_004208.4(AIFM1):c.784G>A (p.Gly262Ser) SNV Pathogenic 732670 rs1603224817 X:129273844-129273844 X:130139869-130139869
3 RAB33A NM_004208.4(AIFM1):c.422C>T (p.Thr141Ile) SNV Pathogenic 732674 rs1603227409 X:129281779-129281779 X:130147804-130147804
4 RAB33A NM_004208.4(AIFM1):c.1388G>T (p.Arg463Ile) SNV Likely pathogenic 243069 rs202219398 X:129267348-129267348 X:130133373-130133373
5 RAB33A NM_004208.4(AIFM1):c.1019T>C (p.Met340Thr) SNV Conflicting interpretations of pathogenicity 374094 rs1057518895 X:129271109-129271109 X:130137134-130137134
6 RAB33A NM_004208.4(AIFM1):c.170C>G (p.Ser57Cys) SNV Uncertain significance 445310 rs201711375 X:129290514-129290514 X:130156540-130156540

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia:

73
# Symbol AA change Variation ID SNP ID
1 AIFM1 p.Glu493Val VAR_069468 rs281864468

Expression for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia.

Pathways for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Pathways related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia according to KEGG:

36
# Name Kegg Source Accession
1 Apoptosis hsa04210
2 Necroptosis hsa04217

GO Terms for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

Sources for Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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