MCID: CHR376
MIFTS: 41

Charcot-Marie-Tooth Disease, Type 4d

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Muscle 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 57 53 29 13 6 40 73
Cmt4d 57 12 53 59 75
Charcot-Marie-Tooth Disease Type 4d 12 53 59 15
Hmsnl 57 12 53 75
Hmsn4d 57 12 75
Neuropathy, Hereditary Motor and Sensory, Lom Type 57 53
Hereditary Motor and Sensory Neuropathy, Lom Type 53 59
Charcot-Marie-Tooth Neuropathy Type 4d 12 75
Hmsn-Lom 12 59
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4d 57
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4d 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4d 75
Neuropathy, Hereditary Motor and Sensory, Lom Type; Hmsnl 57
Hereditary Motor Abd Sensory Neuropathy Lom Type 12
Hereditary Motor and Sensory Neuropathy Lom Type 75
Hereditary Motor and Sensory Neuropathy Ivd 75
Charcot-Marie-Tooth Neuropathy, Type 4d 57
Charcot-Marie-Tooth Disease 4d 75
Hmsn, Lom Type 59
Hmsn Lom Type 12
Hmsn Ivd 75
Nmsl 53

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4d
Inheritance: Autosomal recessive; Age of onset: Adolescent,Childhood; Age of death: normal life expectancy;

OMIM:

57
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:

32
charcot-marie-tooth disease, type 4d:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 601455
Disease Ontology 12 DOID:0110186
ICD10 33 G60.0
Orphanet 59 ORPHA99950
MESH via Orphanet 45 C535716
UMLS via Orphanet 74 C1832334
ICD10 via Orphanet 34 G60.0
MedGen 42 C1832334
UMLS 73 C1832334

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

UniProtKB/Swiss-Prot : 75 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. 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 Neural Stem Cell Differentiation Pathways and Lineage-specific Markers. Related phenotypes are hearing impairment and abnormality of visual evoked potentials

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 : 57 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 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, Type 4b3 Charcot-Marie-Tooth Disease, Recessive Intermediate C
Charcot-Marie-Tooth Disease, Type 4k 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 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
Pmp2-Related Charcot-Marie-Tooth Disease Type 1 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 all 20)
# Related Disease Score Top Affiliating Genes
1 hereditary neuropathies 30.2 GJB1 MFN2 NDRG1
2 neuropathy 29.5 CTDP1 GDAP1 GJB1 MFN2
3 tooth disease 29.4 GDAP1 GJB1 MFN2 NDRG1 SH3TC2 TRPV4
4 charcot-marie-tooth disease 29.4 GDAP1 GJB1 MFN2 NDRG1 SH3TC2 TRPV4
5 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 29.2 CTDP1 GDAP1 GJB1 MFN2 MYCN NDRG1
6 neuropathy, hereditary motor and sensory, russe type 10.4 CTDP1 NDRG1 SH3TC2
7 charcot-marie-tooth disease, demyelinating, type 1d 10.4 GJB1 MYCN NDRG1
8 motor peripheral neuropathy 10.3 GJB1 MFN2 NDRG1
9 neuropathy, hereditary, with liability to pressure palsies 10.2 GDAP1 GJB1 MFN2
10 hypertrophic neuropathy of dejerine-sottas 10.2 GDAP1 GJB1 SH3TC2
11 charcot-marie-tooth disease, axonal, type 2k 10.0 GDAP1 MFN2 TRPV4
12 charcot-marie-tooth disease, x-linked dominant, 1 10.0 GDAP1 GJB1
13 peripheral nervous system disease 10.0 GDAP1 GJB1 MFN2 SH3TC2
14 charcot-marie-tooth disease, axonal, type 2e 9.9 GDAP1 GJB1 MFN2 NDRG1
15 axonal neuropathy 9.9 GDAP1 MFN2 TRPV4
16 charcot-marie-tooth disease, demyelinating, type 1a 9.8 GDAP1 GJB1 MFN2 NTF3
17 hereditary motor and sensory neuropathy, type iic 9.7 GDAP1 GJB1 MFN2 NDRG1 TRPV4
18 sensory peripheral neuropathy 9.6 GDAP1 GJB1 MFN2 NDRG1 NTF3
19 charcot-marie-tooth disease and deafness 9.6 GDAP1 GJB1 MFN2 NTF3 SH3TC2
20 trehalase deficiency 9.2 GJB1 MFN2 MYCN SH3TC2 TRPV4

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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 32 HP:0000365
2 abnormality of visual evoked potentials 32 HP:0000649
3 decreased nerve conduction velocity 32 HP:0000762
4 abnormality of the hand 32 HP:0001155
5 hyporeflexia 32 HP:0001265
6 areflexia 32 HP:0001284
7 gait disturbance 32 HP:0001288
8 distal muscle weakness 32 HP:0002460
9 distal sensory impairment 32 HP:0002936
10 onion bulb formation 32 HP:0003383
11 axonal loss 32 HP:0003447
12 segmental peripheral demyelination/remyelination 32 HP:0003481
13 distal amyotrophy 32 HP:0003693
14 talipes cavus equinovarus 32 HP:0004696
15 intraaxonal accumulation of curvilinear autofluorescent lipopigment storage material 32 HP:0006916
16 abnormal auditory evoked potentials 32 HP:0006958

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.18 NDRG4 NTF3 OLIG2 SH3TC2 TRPV4 GDAP1
2 homeostasis/metabolism MP:0005376 10.06 LDLR MFN2 MYCN NDRG1 NDRG2 NDRG4
3 mortality/aging MP:0010768 10 MFN2 MYCN NDRG1 NDRG2 NDRG3 NTF3
4 muscle MP:0005369 9.81 GDNF LDLR MFN2 MYCN NDRG1 NTF3
5 nervous system MP:0003631 9.77 GDAP1 GDNF GJB1 LDLR MFN2 MYCN
6 vision/eye MP:0005391 9.17 GJB1 LDLR MYCN NDRG1 NTF3 OLIG2

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

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

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

# Title Authors Year
1
Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D. ( 28776325 )
2017

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

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NDRG1 NM_001135242.1(NDRG1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs119483085 GRCh37 Chromosome 8, 134270617: 134270617
2 NDRG1 NM_001135242.1(NDRG1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs119483085 GRCh38 Chromosome 8, 133258374: 133258374
3 NDRG1 NDRG1, IVS8AS-1G-A single nucleotide variant Pathogenic
4 NDRG1 NG_007943.1: g.(43089_43830)_(47717_51712)dup duplication Pathogenic GRCh37 Chromosome 8, 134262787: 134271410
5 NDRG1 NG_007943.1: g.(43089_43830)_(47717_51712)dup duplication Pathogenic GRCh38 Chromosome 8, 133250544: 133259167
6 NDRG1 NC_000008.10: g.134265065_134271319dup duplication Pathogenic GRCh37 Chromosome 8, 134265065: 134271319
7 NDRG1 NM_006096.3(NDRG1): c.64-6T> C single nucleotide variant Benign rs2272653 GRCh37 Chromosome 8, 134292516: 134292516
8 NDRG1 NM_006096.3(NDRG1): c.64-6T> C single nucleotide variant Benign rs2272653 GRCh38 Chromosome 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 NDRG1 NDRG2 NDRG3 NDRG4
2 11.33 GDNF NTF3 OLIG2
3 11.29 MYCN NDRG1 NDRG2 NDRG3 NDRG4
4 11.21 NDRG1 NDRG2 NDRG3 NDRG4

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 recycling endosome GO:0055037 8.8 EEA1 RAB4A SH3TC2

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

# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.43 GDNF GJB1 MYLIP NDRG2 NTF3 OLIG2
2 peripheral nervous system development GO:0007422 9.32 GDNF NTF3
3 mitochondrial fusion GO:0008053 9.26 GDAP1 MFN2
4 peripheral nervous system myelin maintenance GO:0032287 9.16 NDRG1 SH3TC2
5 negative regulation of smooth muscle cell proliferation GO:0048662 8.8 MFN2 NDRG2 NDRG4

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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