CMTX4
MCID: CHR696
MIFTS: 31

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 56
Cowchock Syndrome 56 58 73 36 29 13 6 39
Cmtx4 56 58 73
Charcot-Marie-Tooth Disease with Deafness and Mental Retardation 56 73
Cowck 56 73
Namsd 56 73
Nadmr 56 73
Neuropathy, Axonal Motor-Sensory, with Deafness and Mental Retardation; Namsd 56
Neuropathy, Axonal Motor-Sensory, with Deafness and Mental Retardation 56
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 56
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:

56
Miscellaneous:
onset in infancy or early childhood

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


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

OMIM : 56 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)

MalaCards based summary : Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia, also known as cowchock syndrome, is related to x-linked charcot-marie-tooth disease and charcot-marie-tooth disease x-linked recessive 4. 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 skeletal muscle atrophy and areflexia

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 Cowchock syndrome: An X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment.

Wikipedia : 74 Charcot-Marie-Tooth disease (CMT) is one of the hereditary motor and sensory neuropathies of the... more...

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

Diseases related to Charcot-Marie-Tooth Disease, X-Linked Recessive, 4, with or Without Cerebellar Ataxia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 x-linked charcot-marie-tooth disease 11.4
2 charcot-marie-tooth disease x-linked recessive 4 11.3
3 neuropathy, congenital hypomyelinating, 1, autosomal recessive 10.4
4 charcot-marie-tooth disease 10.4
5 tooth disease 10.4
6 sensory peripheral neuropathy 10.4
7 neuropathy 10.3
8 branchiootic syndrome 1 10.1
9 axonal neuropathy 10.1
10 mitochondrial encephalomyopathy 10.1
11 charcot-marie-tooth neuropathy x type 1 10.1
12 charcot-marie-tooth neuropathy x type 5 10.1

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:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
2 areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001284
3 sensory neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000763
4 decreased nerve conduction velocity 58 31 hallmark (90%) Very frequent (99-80%) HP:0000762
5 pes cavus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001761
6 sensorimotor neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007141
7 distal muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0002460
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
10 kyphosis 58 31 frequent (33%) Frequent (79-30%) HP:0002808
11 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
12 impaired pain sensation 58 31 frequent (33%) Frequent (79-30%) HP:0007328
13 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
14 gait disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0001288
15 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
16 sleep disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0002360
17 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
18 cognitive impairment 31 occasional (7.5%) HP:0100543
19 muscle weakness 31 HP:0001324
20 motor axonal neuropathy 31 HP:0007002
21 sensory axonal neuropathy 31 HP:0003390
22 distal sensory impairment 31 HP:0002936
23 elevated serum creatine kinase 31 HP:0003236

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
increased serum creatine kinase
increased serum transaminases

Neurologic Central Nervous System:
cognitive impairment (in some patients)
t2-weighted hyperintensities in the supratentorial white matter seen on brain mri

Neurologic Peripheral Nervous System:
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)

Head And Neck Ears:
hearing loss, sensorineural (in some patients)

Muscle Soft Tissue:
distal muscle weakness due to peripheral neuropathy
distal muscle wasting due to peripheral neuropathy
neurogenic atrophy see on muscle biopsy
increased numbers of abnormally-shaped mitochondria in subsarcolemmal areas

Clinical features from OMIM:

310490

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
Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. 56 6 61
23217327 2012
2
X-linked motor-sensory neuropathy type-II with deafness and mental retardation: a new disorder. 56 6
3856385 1985
3
Clinical spectrum of AIFM1-associated disease in an Irish family, from mild neuropathy to severe cerebellar ataxia with colour blindness. 61 56
31523922 2019
4
Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin. 56
28967629 2018
5
A slowly progressive mitochondrial encephalomyopathy widens the spectrum of AIFM1 disorders. 56
25934856 2015
6
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
7
A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq24-q26. 56
8666389 1995
8
X-linked neuropathy: gene localization with DNA probes. 56
3024556 1986
9
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017
10
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 AIFM1 NM_004208.4(AIFM1):c.1478A>T (p.Glu493Val)SNV Pathogenic 39601 rs281864468 X:129265745-129265745 X:130131770-130131770
2 AIFM1 NM_004208.4(AIFM1):c.1019T>C (p.Met340Thr)SNV Likely pathogenic 374094 rs1057518895 X:129271109-129271109 X:130137134-130137134
3 AIFM1 NM_004208.4(AIFM1):c.1388G>T (p.Arg463Ile)SNV Conflicting interpretations of pathogenicity 243069 rs202219398 X:129267348-129267348 X:130133373-130133373
4 AIFM1 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
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
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43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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