MCID: CHR517
MIFTS: 41

Charcot-Marie-Tooth Disease, Type 4a

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Muscle diseases, Metabolic diseases, Fetal diseases, Ear diseases

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

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

Name: Charcot-Marie-Tooth Disease, Type 4a 54 29 13 69
Charcot-Marie-Tooth Disease Type 4a 12 50 24 56 14
Cmt4a 12 50 24 56 71
Charcot-Marie-Tooth Neuropathy Type 4a 12 24
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive, Type 4a 71
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4a 12
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive 50
Charcot-Marie-Tooth Disease Neuropathy Type 4a 71
Charcot Marie Tooth Disease Type 4a 50
Charcot-Marie-Tooth Disease 4a 71
Cmt 4a 24

Characteristics:

Orphanet epidemiological data:

56
charcot-marie-tooth disease type 4a
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity
usually begins in feet and legs (peroneal distribution)
upper limb involvement usually occurs later
onset before age 2 years
rapid progression to disability


HPO:

32
charcot-marie-tooth disease, type 4a:
Onset and clinical course rapidly progressive infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


External Ids:

OMIM 54 214400
Disease Ontology 12 DOID:0110185
ICD10 33 G60.0
Orphanet 56 ORPHA99948
MESH via Orphanet 43 C535419
UMLS via Orphanet 70 C1859198
ICD10 via Orphanet 34 G60.0
MedGen 40 C1859198
MeSH 42 D002607

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

UniProtKB/Swiss-Prot : 71 Charcot-Marie-Tooth disease 4A: A 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. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4a, also known as charcot-marie-tooth disease type 4a, is related to neuropathy, congenital hypomyelinating and charcot-marie-tooth disease, type 4h, and has symptoms including distal sensory impairment, hyporeflexia and kyphoscoliosis. An important gene associated with Charcot-Marie-Tooth Disease, Type 4a is GDAP1 (Ganglioside Induced Differentiation Associated Protein 1). The drugs 4-des-dimethylaminotetracycline and HIV Protease Inhibitors have been mentioned in the context of this disorder. Related phenotypes are behavior/neurological and nervous system

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in mutation in the gene encoding ganglioside-induced differentiation-associated protein-1 (GDAP1) on chromosome 8q21.

OMIM : 54
By convention, the designation CMT4 is applied to autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease, which is a peripheral neuropathy characterized by distal motor and sensory impairment resulting in gait difficulties and associated with foot deformities. Motor nerve conduction velocities are decreased, and sural nerve biopsies show loss of myelinated fibers. The age at onset and severity is variable (summary by Patzko and Shy, 2012). (214400)

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

Diseases in the Charcot-Marie-Tooth Disease family:

Charcot-Marie-Tooth Disease, Type 2a1 Charcot-Marie-Tooth Disease, Recessive Intermediate C
Charcot-Marie-Tooth Disease, Dominant Intermediate C Charcot-Marie-Tooth Disease, Type 2b1
Charcot-Marie-Tooth Disease, Type 1b Charcot-Marie-Tooth Disease, Type 2j
Charcot-Marie-Tooth Disease, Type 2i Charcot-Marie-Tooth Disease, Type 2b
Charcot-Marie-Tooth Disease, Type 2r Charcot-Marie-Tooth Disease, Type 4c
Charcot-Marie-Tooth Disease, Type 4j Charcot-Marie-Tooth Disease, Type 2d
Charcot-Marie-Tooth Disease, Type 2e Charcot-Marie-Tooth Disease, Type 1f
Charcot-Marie-Tooth Disease, Type 4a Charcot-Marie-Tooth Disease, Recessive Intermediate, a
Charcot-Marie-Tooth Disease, Type 4d Charcot-Marie-Tooth Disease, Type 4k
Charcot-Marie-Tooth Disease, Type 1d Charcot-Marie-Tooth Disease, Dominant Intermediate a
Charcot-Marie-Tooth Disease, Type 4b2 Charcot-Marie-Tooth Disease, Type 4b1
Charcot-Marie-Tooth Disease, Type 4h Charcot-Marie-Tooth Disease, Type 1c
Charcot-Marie-Tooth Disease, Recessive Intermediate, B Charcot-Marie-Tooth Disease, Type 1a
Charcot-Marie-Tooth Disease, Type 1e Charcot-Marie-Tooth Disease, Dominant Intermediate B
Charcot-Marie-Tooth Disease, Type 4f Charcot-Marie-Tooth Disease, Type 2b2
Charcot-Marie-Tooth Disease, Type 4b3 Charcot-Marie-Tooth Disease Intermediate Type
Charcot-Marie-Tooth Disease Type 5 Charcot-Marie-Tooth Disease Type 7
Charcot-Marie-Tooth Disease Type 2a2 Autosomal Dominant Intermediate Charcot-Marie-Tooth
Autosomal Dominant Intermediate Charcot-Marie-Tooth Disease Type B Autosomal Recessive Intermediate Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth Disease Type 2a Charcot-Marie-Tooth Disease Type 2c
Charcot-Marie-Tooth Disease Type 2f Charcot-Marie-Tooth Disease Type 2g
Charcot-Marie-Tooth Disease Type 2k Charcot-Marie-Tooth Disease Type 2l
Charcot-Marie-Tooth Disease Type 2n Charcot-Marie-Tooth Disease Type 2o
Charcot-Marie-Tooth Disease Type 2q Charcot-Marie-Tooth Disease Type 2b5
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Kif5a Mutation Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Tfg Mutation
Charcot-Marie-Tooth Disease Type 2t Pmp2-Related Charcot-Marie-Tooth Disease Type 1
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2w Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Dgat2 Mutation

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

(show all 43)
id Related Disease Score Top Affiliating Genes
1 neuropathy, congenital hypomyelinating 28.4 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2
2 charcot-marie-tooth disease, type 4h 11.5
3 charcot-marie-tooth disease, type 4c 11.5
4 charcot-marie-tooth disease type 2g 11.3
5 charcot-marie-tooth disease, axonal, type 2k 10.9
6 neuropathy, hereditary motor and sensory, russe type 10.7
7 charcot-marie-tooth disease, type 4b2 10.7
8 charcot-marie-tooth disease, type 4f 10.7
9 charcot-marie-tooth disease, type 2a1 10.7
10 charcot-marie-tooth disease, axonal, type 2a2a 10.7
11 charcot-marie-tooth disease, type 4j 10.7
12 charcot-marie-tooth disease, type 4d 10.7
13 charcot-marie-tooth disease, type 4k 10.7
14 charcot-marie-tooth disease, type 2b1 10.4 GDAP1 JPH1
15 charcot-marie-tooth disease 10.3
16 tooth disease 10.3
17 glaucoma 1, open angle, 1o 10.3 GDAP1 JPH1
18 neuropathy 10.2
19 charcot-marie-tooth neuropathy 10.2
20 neuronitis 10.2
21 neuropathy, inflammatory demyelinating 10.1 GDAP1 MTMR2
22 white piedra 10.1 GDAP1 TUBB3
23 charcot-marie-tooth neuropathy x 10.1 GDAP1 SBF2
24 multiple epiphyseal dysplasia with robin phenotype 10.0 GDAP1 JPH1
25 charcot-marie-tooth disease, recessive intermediate, a 10.0 GDAP1 JPH1 TUBB3
26 familial male-limited precocious puberty 10.0 MTMR2 SBF2
27 hypoxia 10.0 MTMR2 PRX
28 pancreatic acinar cell adenocarcinoma 9.9 GDAP1 MTMR2 TUBB3
29 dejerine-sottas disease 9.8 GDAP1 MTMR2 PRX
30 senile angioma 9.8 GDAP1 MTMR2 PRX
31 hereditary angioedema 9.8 MTMR2 SBF2
32 short stature, idiopathic familial 9.8 GDAP1 MTMR2 SBF2
33 amyotrophic lateral sclerosis 11 9.7 GDAP1 MTMR2 SBF2
34 pseudosarcomatous fibromatosis 9.7 GDAP1 TDP1
35 decubitus ulcer 9.6 GDAP1 PRX TDP1
36 congestive heart failure 9.6 MTMR2 PRX SBF2
37 hermansky-pudlak syndrome 5 9.3 GDAP1 MTMR2 PRX SBF2
38 progesterone resistance 9.2 GDAP1 MTMR2 PRX SBF2
39 amnestic disorder 9.2 GDAP1 MTMR2 PRX SBF2
40 charcot-marie-tooth disease, type 1f 9.0 GDAP1 JPH1 MTMR2 SBF2 TUBB3
41 chromosome 19q13.11 deletion syndrome, distal 8.7 GDAP1 MTMR2 PRX SBF2 TDP1
42 childhood-onset cerebral x-linked adrenoleukodystrophy 8.0 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2
43 charcot-marie-tooth disease, axonal, with vocal cord paresis 7.1 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2

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



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

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

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Peripheral Nervous System:
delayed motor development
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
distal sensory impairment
hyporeflexia
more
Skeletal- Spine:
kyphoscoliosis may occur

Skeletal- Feet:
foot deformities may occur

Skeletal- Hands:
claw hand deformities (in severe cases)


Clinical features from OMIM:

214400

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

32 (show all 18)
id Description HPO Frequency HPO Source Accession
1 distal sensory impairment 32 HP:0002936
2 hyporeflexia 32 HP:0001265
3 kyphoscoliosis 32 frequent (33%) HP:0002751
4 areflexia 32 HP:0001284
5 motor delay 32 HP:0001270
6 hypertrophic nerve changes 32 HP:0003382
7 distal muscle weakness 32 HP:0002460
8 distal amyotrophy 32 HP:0003693
9 split hand 32 HP:0001171
10 inability to walk by childhood/adolescence 32 HP:0006915
11 decreased motor nerve conduction velocity 32 HP:0003431
12 hammertoe 32 HP:0001765
13 cns hypomyelination 32 HP:0003429
14 decreased number of peripheral myelinated nerve fibers 32 HP:0003380
15 ulnar claw 32 HP:0001178
16 peripheral axonal degeneration 32 HP:0000764
17 basal lamina 'onion bulb' formation 32 HP:0003400
18 peripheral hypomyelination 32 HP:0007182

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Type 4a:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.5 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2
2 nervous system MP:0003631 9.17 GDAP1 MTMR2 PMP2 PRX SBF2 TDP1

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

Drugs for Charcot-Marie-Tooth Disease, Type 4a (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 4-des-dimethylaminotetracycline
2 HIV Protease Inhibitors
3 Matrix Metalloproteinase Inhibitors
4
protease inhibitors

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others Recruiting NCT01193075

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

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

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

id Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4a 29
2 Charcot-Marie-Tooth Neuropathy Type 4a 24 GDAP1

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

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

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

id Title Authors Year
1
Genetics of Charcot-Marie-Tooth disease type 4A: mutations, inheritance, phenotypic variability, and founder effect. ( 15805163 )
2005
2
GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria. ( 15772096 )
2005

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

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Type 4a:

71
id Symbol AA change Variation ID SNP ID
1 GDAP1 p.Arg120Gln VAR_017184
2 GDAP1 p.Arg161His VAR_017185 rs104894076

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

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 GDAP1 NM_018972.2(GDAP1): c.92G> A (p.Trp31Ter) single nucleotide variant Pathogenic rs121908112 GRCh37 Chromosome 8, 75262788: 75262788
2 GDAP1 NM_018972.2(GDAP1): c.581C> G (p.Ser194Ter) single nucleotide variant Pathogenic rs104894075 GRCh37 Chromosome 8, 75275175: 75275175
3 GDAP1 NM_018972.2(GDAP1): c.482G> A (p.Arg161His) single nucleotide variant Pathogenic rs104894076 GRCh37 Chromosome 8, 75272543: 75272543
4 GDAP1 NM_018972.2(GDAP1): c.487C> T (p.Gln163Ter) single nucleotide variant Pathogenic rs104894077 GRCh37 Chromosome 8, 75274121: 75274121
5 GDAP1 NM_018972.2(GDAP1): c.358C> T (p.Arg120Trp) single nucleotide variant Pathogenic rs104894078 GRCh37 Chromosome 8, 75272419: 75272419
6 GDAP1 NM_018972.2(GDAP1): c.715C> T (p.Leu239Phe) single nucleotide variant Pathogenic rs104894080 GRCh37 Chromosome 8, 75276240: 75276240
7 GDAP1 NM_018972.2(GDAP1): c.347T> G (p.Met116Arg) single nucleotide variant Pathogenic rs281865060 GRCh37 Chromosome 8, 75272408: 75272408
8 GDAP1 NM_018972.2(GDAP1): c.373C> T (p.Arg125Ter) single nucleotide variant Pathogenic rs745663149 GRCh38 Chromosome 8, 74360199: 74360199
9 GDAP1 NM_018972.2(GDAP1): c.579+1G> A single nucleotide variant Pathogenic rs864622501 GRCh37 Chromosome 8, 75274214: 75274214
10 GDAP1 NM_018972.2(GDAP1): c.579delA (p.Lys193Asnfs) deletion Pathogenic rs1060500979 GRCh38 Chromosome 8, 74361978: 74361978
11 GDAP1 NM_018972.2(GDAP1): c.786delG (p.Phe263Leufs) deletion Likely pathogenic rs1060500978 GRCh38 Chromosome 8, 74364076: 74364076
12 GDAP1 NM_018972.2(GDAP1): c.1019dupT (p.Arg341Glnfs) duplication Likely pathogenic GRCh38 Chromosome 8, 74364309: 74364309
13 GDAP1 NM_018972.2(GDAP1): c.311-1790_408del deletion Likely pathogenic GRCh38 Chromosome 8, 74358347: 74360234

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

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

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

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

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

id Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.5 GDAP1 MTMR2 PMP2 PRX SBF2 TDP1
2 vacuolar membrane GO:0005774 8.62 MTMR2 SBF2

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

id Name GO ID Score Top Affiliating Genes
1 protein tetramerization GO:0051262 8.62 MTMR2 SBF2

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
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34 ICD10 via Orphanet
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43 MESH via Orphanet
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59 PubMed
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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