CMT4K
MCID: CHR609
MIFTS: 34

Charcot-Marie-Tooth Disease, Type 4k (CMT4K)

Categories: Ear diseases, Eye diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Charcot-Marie-Tooth Disease, Type 4k

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Type 4k:

Name: Charcot-Marie-Tooth Disease, Type 4k 57 29 6
Cmt4k 57 12 58 72
Charcot-Marie-Tooth Disease Type 4k 12 58 15
Charcot-Marie-Tooth Neuropathy, Demyelinating, Autosomal Recessive, Type 4k 57 72
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4k 57 72
Surf1-Related Severe Demyelinating Charcot-Marie-Tooth Disease 12 58
Surf1-Related Charcot-Marie-Tooth Disease Type 4 12 58
Surf1-Related Cmt4 12 58
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Neuropathy Type 4k 12
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4k 12
Charcot-Marie-Tooth Disease, Demyelinating, Type 4k 72
Charcot-Marie-Tooth Neuropathy, Type 4k 72
Charcot-Marie-Tooth Disease 4k 72

Characteristics:

Orphanet epidemiological data:

58
surf1-related charcot-marie-tooth disease type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

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

Miscellaneous:
variable severity
slowly progressive
onset in first decade
three patients from 2 unrelated families have been reported (last curated december 2015)


HPO:

31
charcot-marie-tooth disease, type 4k:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0110187
OMIM® 57 616684
OMIM Phenotypic Series 57 PS118220
MeSH 44 D002607
ICD10 32 G60.0
ICD10 via Orphanet 33 G60.0
Orphanet 58 ORPHA391351

Summaries for Charcot-Marie-Tooth Disease, Type 4k

UniProtKB/Swiss-Prot : 72 Charcot-Marie-Tooth disease 4K: An autosomal recessive, demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4K patients manifest upper and lower limbs involvement. Some affected individuals have nystagmus and late-onset cerebellar ataxia.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4k, also known as cmt4k, is related to cardiomyopathy, infantile hypertrophic and cardioencephalomyopathy. An important gene associated with Charcot-Marie-Tooth Disease, Type 4k is SURF1 (SURF1 Cytochrome C Oxidase Assembly Factor), and among its related pathways/superpathways is Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Affiliated tissues include eye and skeletal muscle, and related phenotypes are ataxia and sensorineural hearing impairment

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in homozygous or compound heterozygous mutation in the SURF1 gene on chromosome 9q34.

OMIM® : 57 Charcot-Marie-Tooth disease type 4K is an autosomal recessive demyelinating peripheral neuropathy characterized by onset in the first decade of distal muscle weakness and atrophy associated with impaired distal sensation. Both upper and lower limbs are affected. Affected individuals may also have nystagmus and late-onset cerebellar ataxia. Laboratory studies show increased serum lactate and isolated mitochondrial complex IV deficiency (summary by Echaniz-Laguna et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400). (616684) (Updated 20-May-2021)

Related Diseases for Charcot-Marie-Tooth Disease, Type 4k

Diseases in the Charcot-Marie-Tooth Disease family:

Charcot-Marie-Tooth Disease, Type 4a Charcot-Marie-Tooth Disease, Type 4b1
Charcot-Marie-Tooth Disease, Type 4d Charcot-Marie-Tooth Disease, Type 4c
Charcot-Marie-Tooth Disease, Type 4b2 Charcot-Marie-Tooth Disease, Dominant Intermediate B
Charcot-Marie-Tooth Disease, Dominant Intermediate a Charcot-Marie-Tooth Disease, Dominant Intermediate D
Charcot-Marie-Tooth Disease, Dominant Intermediate C Charcot-Marie-Tooth Disease, Recessive Intermediate a
Charcot-Marie-Tooth Disease, Type 4h Charcot-Marie-Tooth Disease, Type 4j
Charcot-Marie-Tooth Disease, Recessive Intermediate B Charcot-Marie-Tooth Disease, Dominant Intermediate E
Charcot-Marie-Tooth Disease, Dominant Intermediate F Charcot-Marie-Tooth Disease, Type 4b3
Charcot-Marie-Tooth Disease, Recessive Intermediate C Charcot-Marie-Tooth Disease, Recessive Intermediate D
Charcot-Marie-Tooth Disease, Type 4k Charcot-Marie-Tooth Disease, Dominant Intermediate G
Charcot-Marie-Tooth Disease Type X Charcot-Marie-Tooth Disease Intermediate Type
Charcot-Marie-Tooth Disease Type 5 Charcot-Marie-Tooth Disease Type 7
Charcot-Marie-Tooth Disease Type 2a2a Charcot-Marie-Tooth Disease Type 2a2b
Charcot-Marie-Tooth Disease Type 1g Autosomal Dominant Intermediate Charcot-Marie-Tooth
Autosomal Recessive Intermediate Charcot-Marie-Tooth Disease Charcot-Marie-Tooth Disease Type 2a
Charcot-Marie-Tooth Disease Type 2l Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Kif5a Mutation
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Tfg Mutation Dnajb2-Related Charcot-Marie-Tooth Disease Type 2
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Dgat2 Mutation Autosomal Dominant Charcot-Marie-Tooth Disease Type 2g

Diseases related to Charcot-Marie-Tooth Disease, Type 4k via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 cardiomyopathy, infantile hypertrophic 10.2 SURF1 PET117
2 cardioencephalomyopathy 10.1 SURF1 COA5
3 neuropathy, ataxia, and retinitis pigmentosa 10.1 SURF1 COA5
4 neuropathy, hereditary sensory and autonomic, type ic 10.0 SH3TC2 LITAF
5 charcot-marie-tooth disease intermediate type 10.0 SH3TC2 LITAF
6 charcot-marie-tooth disease type x 10.0 SH3TC2 LITAF
7 charcot-marie-tooth disease, demyelinating, type 4f 10.0 SH3TC2 LITAF
8 charcot-marie-tooth disease, dominant intermediate b 10.0 SH3TC2 LITAF
9 charcot-marie-tooth disease, x-linked dominant, 1 10.0 SH3TC2 LITAF
10 charcot-marie-tooth disease, type 4a 10.0 SH3TC2 LITAF
11 charcot-marie-tooth disease, type 4d 10.0 SH3TC2 LITAF
12 charcot-marie-tooth disease, axonal, type 2b 10.0 SH3TC2 LITAF
13 mitochondrial dna depletion syndrome 9 10.0 PET100 COA5
14 charcot-marie-tooth disease, demyelinating, type 1b 10.0 SH3TC2 LITAF
15 charcot-marie-tooth disease, type 4j 10.0 SH3TC2 LITAF
16 mitochondrial complex iv deficiency, nuclear type 1 10.0 SURF1 PET117 PET100
17 charcot-marie-tooth disease, type 4c 10.0 SH3TC2 LITAF
18 charcot-marie-tooth disease, type 4b1 10.0 SH3TC2 LITAF
19 leigh syndrome with leukodystrophy 10.0 SURF1 PET100
20 neuropathy, hereditary, with liability to pressure palsies 10.0 SH3TC2 LITAF
21 charcot-marie-tooth disease, demyelinating, type 1a 10.0 SH3TC2 LITAF
22 charcot-marie-tooth disease, demyelinating, type 1c 9.9 SH3TC2 LITAF
23 mitochondrial complex i deficiency, nuclear type 1 9.9 SURF1 PET117 PET100
24 charcot-marie-tooth disease, type 4b2 9.9 SH3TC2 LITAF
25 hereditary sensory and autonomic neuropathy type 1 9.9 SH3TC2 LITAF
26 tooth disease 9.9 SURF1 SH3TC2 LITAF
27 motor peripheral neuropathy 9.9 SH3TC2 LITAF
28 fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency 9.8 SURF1 NDUFAF7 COA5
29 mitochondrial complex iv deficiency, nuclear type 5 9.8 UQCC3 SURF1
30 hypertrophic neuropathy of dejerine-sottas 9.8 SH3TC2 LITAF
31 charcot-marie-tooth disease and deafness 9.7 SH3TC2 LITAF
32 lactic acidosis 9.6 UQCC3 SURF1 PET100
33 leigh syndrome 9.6 SURF1 PET100 NDUFAF7 COA5

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Type 4k:



Diseases related to Charcot-Marie-Tooth Disease, Type 4k

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Type 4k

Human phenotypes related to Charcot-Marie-Tooth Disease, Type 4k:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 sensorineural hearing impairment 31 HP:0000407
3 skeletal muscle atrophy 31 HP:0003202
4 kyphoscoliosis 31 HP:0002751
5 easy fatigability 31 HP:0003388
6 areflexia 31 HP:0001284
7 increased serum lactate 31 HP:0002151
8 dystonia 31 HP:0001332
9 peripheral neuropathy 31 HP:0009830
10 difficulty walking 31 HP:0002355
11 horizontal nystagmus 31 HP:0000666
12 peripheral demyelination 31 HP:0011096
13 axonal loss 31 HP:0003447

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
nystagmus

Laboratory Abnormalities:
increased serum lactate

Head And Neck Ears:
hearing loss, sensorineural, mild

Neurologic Central Nervous System:
cerebellar ataxia, late-onset (in some patients)
hyperintense lesions in the putamina (1 patient)
periaqueductal white matter lesions (1 patient)

Skeletal Spine:
kyphoscoliosis

Neurologic Peripheral Nervous System:
difficulty walking
hypo- or areflexia
sural nerve biopsy shows axonal loss
demyelinating sensorimotor peripheral neuropathy
sural nerve biopsy shows hypomyelinated fibers

Muscle Soft Tissue:
distal muscle weakness, upper and lower limbs, due to peripheral neuropathy
distal muscle atrophy, upper and lower limbs, due to peripheral neuropathy mitochondrial complex iv deficiency

Clinical features from OMIM®:

616684 (Updated 20-May-2021)

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Type 4k

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Type 4k

Genetic Tests for Charcot-Marie-Tooth Disease, Type 4k

Genetic tests related to Charcot-Marie-Tooth Disease, Type 4k:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4k 29 SURF1

Anatomical Context for Charcot-Marie-Tooth Disease, Type 4k

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Type 4k:

40
Eye, Skeletal Muscle

Publications for Charcot-Marie-Tooth Disease, Type 4k

Articles related to Charcot-Marie-Tooth Disease, Type 4k:

# Title Authors PMID Year
1
SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. 6 57
24027061 2013

Variations for Charcot-Marie-Tooth Disease, Type 4k

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Type 4k:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SURF1 NM_003172.4(SURF1):c.574C>T (p.Arg192Trp) SNV Pathogenic 215235 rs782190413 GRCh37: 9:136219563-136219563
GRCh38: 9:133352708-133352708
2 SURF1 NM_003172.4(SURF1):c.841_842CT[2] (p.Ser282fs) Microsatellite Pathogenic 12770 rs782316919 GRCh37: 9:136218825-136218826
GRCh38: 9:133351970-133351971
3 SURF1 NM_003172.4(SURF1):c.312_321delinsAT (p.Pro104_Leu105insTer) Indel Pathogenic 215237 rs863224228 GRCh37: 9:136221516-136221525
GRCh38: 9:133354661-133354670
4 SURF1 NM_003172.4(SURF1):c.688C>T (p.Arg230Ter) SNV Pathogenic 280010 rs782623477 GRCh37: 9:136219364-136219364
GRCh38: 9:133352509-133352509
5 SURF1 NM_003172.4(SURF1):c.240+1G>T SNV Pathogenic 379506 rs781948238 GRCh37: 9:136221678-136221678
GRCh38: 9:133354823-133354823
6 SURF1 NM_003172.4(SURF1):c.574_575insCTGC (p.Arg192fs) Insertion Pathogenic 419973 rs782289759 GRCh37: 9:136219562-136219563
GRCh38: 9:133352707-133352708
7 SURF1 NM_003172.4(SURF1):c.790_791AG[1] (p.Arg264fs) Microsatellite Pathogenic 215238 rs782490558 GRCh37: 9:136218956-136218957
GRCh38: 9:133352101-133352102
8 SURF1 NM_003172.4(SURF1):c.833+1G>A SNV Pathogenic 599351 rs782609482 GRCh37: 9:136218915-136218915
GRCh38: 9:133352060-133352060
9 SURF1 NM_003172.4(SURF1):c.797_798CT[1] (p.Leu267fs) Microsatellite Pathogenic 218303 rs864309500 GRCh37: 9:136218949-136218950
GRCh38: 9:133352094-133352095
10 SURF1 NM_003172.4(SURF1):c.107-2A>G SNV Pathogenic 218301 rs782726390 GRCh37: 9:136221814-136221814
GRCh38: 9:133354959-133354959
11 SURF1 NM_003172.4(SURF1):c.378T>G (p.Phe126Leu) SNV Uncertain significance 1033570 GRCh37: 9:136220741-136220741
GRCh38: 9:133353886-133353886
12 SURF1 NM_003172.4(SURF1):c.808_814dup (p.Leu272fs) Duplication Uncertain significance 548531 rs1554768224 GRCh37: 9:136218934-136218935
GRCh38: 9:133352079-133352080
13 SURF1 NM_003172.4(SURF1):c.588+1G>A SNV not provided 548703 rs1219762677 GRCh37: 9:136219548-136219548
GRCh38: 9:133352693-133352693

Expression for Charcot-Marie-Tooth Disease, Type 4k

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Type 4k.

Pathways for Charcot-Marie-Tooth Disease, Type 4k

GO Terms for Charcot-Marie-Tooth Disease, Type 4k

Cellular components related to Charcot-Marie-Tooth Disease, Type 4k according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.17 UQCC3 SURF1 PET117 PET100 NDUFAF7 COA7
2 integral component of mitochondrial inner membrane GO:0031305 8.96 UQCC3 PET100

Biological processes related to Charcot-Marie-Tooth Disease, Type 4k according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex IV assembly GO:0033617 8.92 SURF1 PET117 PET100 COA5

Sources for Charcot-Marie-Tooth Disease, Type 4k

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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