CMT4D
MCID: CHR376
MIFTS: 43

Charcot-Marie-Tooth Disease, Type 4d (CMT4D)

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

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

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

Name: Charcot-Marie-Tooth Disease, Type 4d 56 52 29 13 6 39 71
Cmt4d 56 12 52 58 73
Charcot-Marie-Tooth Disease Type 4d 12 52 58 15
Hmsnl 56 12 52 73
Hmsn4d 56 12 73
Neuropathy, Hereditary Motor and Sensory, Lom Type 56 52
Hereditary Motor and Sensory Neuropathy, Lom Type 52 58
Charcot-Marie-Tooth Neuropathy Type 4d 12 73
Hmsn-Lom 12 58
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4d 56
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4d 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4d 73
Neuropathy, Hereditary Motor and Sensory, Lom Type; Hmsnl 56
Hereditary Motor Abd Sensory Neuropathy Lom Type 12
Hereditary Motor and Sensory Neuropathy Lom Type 73
Hereditary Motor and Sensory Neuropathy Ivd 73
Charcot-Marie-Tooth Neuropathy, Type 4d 56
Charcot-Marie-Tooth Disease 4d 73
Hmsn, Lom Type 58
Hmsn Lom Type 12
Hmsn Ivd 73
Nmsl 52

Characteristics:

Orphanet epidemiological data:

58
charcot-marie-tooth disease type 4d
Inheritance: Autosomal recessive; Age of onset: Adolescent,Childhood; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
usually begins in feet and legs (peroneal distribution)
upper limb involvement usually occurs later
onset in first decade
first described in gypsy group from bulgaria


HPO:

31
charcot-marie-tooth disease, type 4d:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110186
OMIM 56 601455
OMIM Phenotypic Series 56 PS118220
ICD10 32 G60.0
MESH via Orphanet 44 C535716
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 72 C1832334
Orphanet 58 ORPHA99950
MedGen 41 C1832334
UMLS 71 C1832334

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

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 4D: 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.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4d, also known as cmt4d, is related to hereditary neuropathies and neuropathy, hereditary motor and sensory, russe type. An important gene associated with Charcot-Marie-Tooth Disease, Type 4d is NDRG1 (N-Myc Downstream Regulated 1), and among its related pathways/superpathways are PI3K / Akt Signaling and Apoptosis and Autophagy. Affiliated tissues include bone and eye, and related phenotypes are gait disturbance and hearing impairment

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in homozygous mutation in the N-myc downstream-regulated gene-1 (NDRG1) on chromosome 8q24.

OMIM : 56 Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive disorder of the peripheral nervous system characterized by early-onset distal muscle weakness and atrophy, foot deformities, and sensory loss affecting all modalities. Affected individuals develop deafness by the third decade of life (summary by Okamoto et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive Charcot-Marie-Tooth disease, see CMT4A (214400). (601455)

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

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 4d via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 72)
# Related Disease Score Top Affiliating Genes
1 hereditary neuropathies 29.8 NDRG1 MTMR2 MPZ GJB1
2 neuropathy, hereditary motor and sensory, russe type 29.7 SH3TC2 NDRG1 GDAP1 EGR2 CTDP1
3 neuropathy 28.9 SH3TC2 SBF2 MTMR2 MPZ GJB1 GDAP1
4 polyneuropathy 28.8 SH3TC2 MPZ LITAF GJB1 GDAP1 EGR2
5 neuropathy, congenital hypomyelinating, 1, autosomal recessive 28.3 SH3TC2 SBF2 RAB4A NDRG1 MTMR2 MPZ
6 tooth disease 28.2 SH3TC2 SBF2 NDRG1 MTMR2 MPZ LITAF
7 sensory peripheral neuropathy 28.0 SH3TC2 SBF2 NDRG1 MTMR2 MPZ LITAF
8 charcot-marie-tooth disease 28.0 SH3TC2 SBF2 NDRG1 MTMR2 MPZ LITAF
9 peripheral nervous system disease 27.8 SH3TC2 SBF2 MTMR2 MPZ LITAF GJB1
10 autosomal recessive disease 10.4
11 tremor 10.4
12 sensorineural hearing loss 10.3
13 muscular atrophy 10.3
14 early-onset glaucoma 10.3 SBF2 MTMR2
15 neuropathy, hereditary sensory and autonomic, type ic 10.3 SH3TC2 LITAF
16 charcot-marie-tooth disease, type 4k 10.2 SH3TC2 LITAF
17 argyll robertson pupil 10.2 MPZ GDAP1
18 pupil disease 10.2 MPZ GDAP1
19 charcot-marie-tooth disease, axonal, type 2p 10.2 LITAF GDAP1
20 branchiootic syndrome 1 10.2
21 demyelinating polyneuropathy 10.2
22 charcot-marie-tooth disease, axonal, type 2a1 10.2 MPZ GDAP1
23 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
24 charcot-marie-tooth disease, axonal, type 2l 10.1 MPZ GDAP1
25 hereditary sensory and autonomic neuropathy type 1 10.1 SH3TC2 LITAF GDAP1
26 charcot-marie-tooth disease, axonal, type 2b2 10.1 MPZ GDAP1
27 charcot-marie-tooth disease, dominant intermediate c 10.1 MPZ GDAP1
28 charcot-marie-tooth disease x-linked recessive 4 10.1 MPZ GJB1
29 autoimmune peripheral neuropathy 10.0 MPZ GJB1
30 mononeuropathy 10.0 SH3TC2 MPZ
31 charcot-marie-tooth disease, type 4b3 10.0 SH3TC2 SBF2 MTMR2 GDAP1
32 yunis-varon syndrome 10.0 SBF2 MTMR2
33 nerve compression syndrome 10.0 SH3TC2 MPZ
34 charcot-marie-tooth disease, axonal, type 2d 9.9 MPZ GJB1 GDAP1
35 charcot-marie-tooth disease, axonal, type 2cc 9.9 MPZ GJB1
36 neuropathy, hereditary sensory and autonomic, type iia 9.9 SH3TC2 LITAF GDAP1 FGD4
37 motor peripheral neuropathy 9.8 SH3TC2 LITAF GJB1 GDAP1
38 corneal dystrophy, fleck 9.8 SBF2 MTMR2
39 charcot-marie-tooth disease, dominant intermediate a 9.8 MPZ GJB1 GDAP1 CTDP1
40 hereditary motor and sensory neuropathy, type iic 9.8 SH3TC2 MPZ GJB1 GDAP1
41 abnormal pupillary function 9.8 MPZ GDAP1 EGR2
42 charcot-marie-tooth disease, axonal, type 2f 9.7 MTMR2 MPZ GJB1 GDAP1
43 charcot-marie-tooth disease, dominant intermediate e 9.7 SH3TC2 SBF2 MTMR2 MPZ GDAP1
44 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.6 MPZ GJB1 EGR2
45 charcot-marie-tooth disease, axonal, type 2q 9.6 MPZ GJB1 EGR2
46 charcot-marie-tooth disease type 2a2a 9.5 SH3TC2 MPZ LITAF GJB1 GDAP1
47 charcot-marie-tooth disease, axonal, type 2i 9.5 SH3TC2 MPZ LITAF GJB1 GDAP1
48 charcot-marie-tooth disease, type 4j 9.5 SH3TC2 SBF2 MTMR2 LITAF GDAP1 FGD4
49 charcot-marie-tooth disease, x-linked recessive, 2 9.4 MPZ LITAF GJB1 EGR2
50 charcot-marie-tooth disease, type 4h 9.4 SH3TC2 SBF2 NDRG1 MTMR2 MPZ GDAP1

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



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

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

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

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 gait disturbance 31 HP:0001288
2 hearing impairment 31 HP:0000365
3 abnormality of visual evoked potentials 31 HP:0000649
4 areflexia 31 HP:0001284
5 decreased nerve conduction velocity 31 HP:0000762
6 hyporeflexia 31 HP:0001265
7 abnormality of the hand 31 HP:0001155
8 distal amyotrophy 31 HP:0003693
9 distal muscle weakness 31 HP:0002460
10 segmental peripheral demyelination/remyelination 31 HP:0003481
11 distal sensory impairment 31 HP:0002936
12 axonal loss 31 HP:0003447
13 talipes cavus equinovarus 31 HP:0004696
14 onion bulb formation 31 HP:0003383
15 abnormal auditory evoked potentials 31 HP:0006958
16 intraaxonal accumulation of curvilinear autofluorescent lipopigment storage material 31 HP:0006916

Symptoms via clinical synopsis from OMIM:

56
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
axonal loss
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
more
Skeletal Hands:
hand deformities

Skeletal Feet:
talipes cavus equinovarus
foot deformities

Head And Neck Ears:
deafness (often in third decade)

Clinical features from OMIM:

601455

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.9 EGR2 FGD4 GDAP1 GJB1 MPZ MTMR2
2 homeostasis/metabolism MP:0005376 9.73 EGR2 GDAP1 GJB1 LITAF MPZ MYCN
3 nervous system MP:0003631 9.44 EGR2 FGD4 GDAP1 GJB1 LITAF MPZ

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

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

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4d 29 NDRG1

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

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

40
Bone, Eye

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

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

(show all 33)
# Title Authors PMID Year
1
Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D. 61 56 6
24136616 2014
2
N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. 56 6
10831399 2000
3
Charcot-Marie-Tooth Neuropathy Type 4 61 6
20301641 1998
4
The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4. 6
17470135 2007
5
Mutation history of the roma/gypsies. 6
15322984 2004
6
Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease. 6
12872253 2003
7
Neuromuscular disorders in the Gypsy ethnic group. A short review. 56
12966699 2003
8
Ultrastructural changes in peripheral nerve in hereditary motor and sensory neuropathy-Lom. 56
10476047 1999
9
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
10
Hereditary motor and sensory neuropathy Lom type in an Italian Gypsy family. 56
9631399 1998
11
Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings. 56
9549516 1998
12
Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24. 56
8841199 1996
13
A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8. 56
8606695 1996
14
Cell and context-dependent sorting of neuropathy-associated protein NDRG1 - insights from canine tissues and primary Schwann cell cultures. 61
31029158 2019
15
A Review of Copy Number Variants in Inherited Neuropathies. 61
30258273 2018
16
A novel homozygous NDRG1 mutation in a Chinese patient with Charcot-Marie-Tooth disease 4D. 61
29724652 2018
17
Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D. 61
28776325 2017
18
A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom. 61
27982524 2017
19
HMSN Lom in 12 Czech patients, with one unusual case due to uniparental isodisomy of chromosome 8. 61
28003645 2017
20
Impaired differentiation of macrophage lineage cells attenuates bone remodeling and inflammatory angiogenesis in Ndrg1 deficient mice. 61
26778110 2016
21
[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital]. 61
26602803 2015
22
Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia. 61
23996628 2013
23
CMT4D (NDRG1 mutation): genotype-phenotype correlations. 61
24028195 2013
24
NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation. 61
23813961 2013
25
Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth. 61
22978647 2013
26
The stretcher spontaneous neurodegenerative mutation models Charcot-Marie-Tooth disease type 4D. 61
24715951 2013
27
NDRG4 protein-deficient mice exhibit spatial learning deficits and vulnerabilities to cerebral ischemia. 61
21636852 2011
28
Ndrg1 in development and maintenance of the myelin sheath. 61
21303696 2011
29
A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy. 61
20582309 2010
30
Genetic study of demyelinating form of autosomal-recessive Charcot-Marie-tooth diseases in a Turkish family. 61
19922348 2009
31
Differential expression patterns of NDRG family proteins in the central nervous system. 61
17998568 2008
32
NDRG1-linked Charcot-Marie-Tooth disease (CMT4D) with central nervous system involvement. 61
17142040 2007
33
Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves. 61
15082788 2004

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

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NDRG1 duplication Pathogenic 218919 8:134265065-134271319
2 NDRG1 NM_001135242.2(NDRG1):c.442C>T (p.Arg148Ter)SNV Pathogenic 5120 rs119483085 8:134270617-134270617 8:133258374-133258374
3 NDRG1 NG_007943.1:g.(43089_43830)_(47717_51712)dupduplication Pathogenic 132796 8:134262787-134271410 8:133250544-133259167
4 NDRG1 NM_006096.4(NDRG1):c.944-1G>TSNV Likely pathogenic 800890 8:134251363-134251363 8:133239120-133239120
5 NDRG1 NM_006096.3(NDRG1):c.538-1G>ASNV Conflicting interpretations of pathogenicity 5121 rs11575976 8:134266839-134266839 8:133254596-133254596
6 NDRG1 NM_001135242.2(NDRG1):c.64-6T>CSNV Benign 259916 rs2272653 8:134292516-134292516 8:133280273-133280273

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

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

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

Pathways related to Charcot-Marie-Tooth Disease, Type 4d according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.42 NDRG4 NDRG3 NDRG2 NDRG1
2 11.29 NDRG4 NDRG3 NDRG2 NDRG1 MYCN
3 11.21 NDRG4 NDRG3 NDRG2 NDRG1

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

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.47 STRADB SBF2 RAB4A NDRG4 NDRG3 NDRG2
2 early endosome membrane GO:0031901 9.43 RAB4A MTMR2 LITAF
3 perinuclear region of cytoplasm GO:0048471 9.35 SBF2 RAB4A NDRG2 NDRG1 MTMR2
4 vacuolar membrane GO:0005774 9.16 SBF2 MTMR2

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

# Name GO ID Score Top Affiliating Genes
1 negative regulation of smooth muscle cell proliferation GO:0048662 9.26 NDRG4 NDRG2
2 protein export from nucleus GO:0006611 9.16 STRADB EGR2
3 peripheral nervous system myelin maintenance GO:0032287 8.96 SH3TC2 NDRG1
4 myelination GO:0042552 8.8 SBF2 MPZ EGR2

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

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
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
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
Content
Loading form....