CMT4D
MCID: CHR376
MIFTS: 34

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

Categories: Genetic diseases, Metabolic diseases, Muscle 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 58 54 30 13 6 41 74
Cmt4d 58 12 54 60 76
Charcot-Marie-Tooth Disease Type 4d 12 54 60 15
Hmsnl 58 12 54 76
Hmsn4d 58 12 76
Neuropathy, Hereditary Motor and Sensory, Lom Type 58 54
Hereditary Motor and Sensory Neuropathy, Lom Type 54 60
Charcot-Marie-Tooth Neuropathy Type 4d 12 76
Hmsn-Lom 12 60
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4d 58
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4d 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4d 76
Neuropathy, Hereditary Motor and Sensory, Lom Type; Hmsnl 58
Hereditary Motor Abd Sensory Neuropathy Lom Type 12
Hereditary Motor and Sensory Neuropathy Lom Type 76
Hereditary Motor and Sensory Neuropathy Ivd 76
Charcot-Marie-Tooth Neuropathy, Type 4d 58
Charcot-Marie-Tooth Disease 4d 76
Hmsn, Lom Type 60
Hmsn Lom Type 12
Hmsn Ivd 76
Nmsl 54

Characteristics:

Orphanet epidemiological data:

60
charcot-marie-tooth disease type 4d
Inheritance: Autosomal recessive; Age of onset: Adolescent,Childhood; Age of death: normal life expectancy;

OMIM:

58
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:

33
charcot-marie-tooth disease, type 4d:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110186
OMIM 58 601455
ICD10 34 G60.0
MESH via Orphanet 46 C535716
ICD10 via Orphanet 35 G60.0
UMLS via Orphanet 75 C1832334
Orphanet 60 ORPHA99950
MedGen 43 C1832334
UMLS 74 C1832334

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

UniProtKB/Swiss-Prot : 76 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 tooth disease 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 Wnt / Hedgehog / Notch and PI3K / Akt Signaling. 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 : 58 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 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 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 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:

# Related Disease Score Top Affiliating Genes
1 tooth disease 30.7 GDAP1 NDRG1
2 neuropathy 30.1 CTDP1 GDAP1
3 sensory peripheral neuropathy 30.0 GDAP1 NDRG1
4 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
5 charcot-marie-tooth disease 10.5
6 charcot-marie-tooth disease, demyelinating, type 1d 9.8 MYCN NDRG1
7 hereditary motor and sensory neuropathy, type iic 9.8 GDAP1 NDRG1
8 neuropathy, hereditary motor and sensory, russe type 9.7 CTDP1 NDRG1

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:

33 (show all 16)
# Description HPO Frequency HPO Source Accession
1 gait disturbance 33 HP:0001288
2 hearing impairment 33 HP:0000365
3 abnormality of visual evoked potentials 33 HP:0000649
4 decreased nerve conduction velocity 33 HP:0000762
5 areflexia 33 HP:0001284
6 abnormality of the hand 33 HP:0001155
7 hyporeflexia 33 HP:0001265
8 distal muscle weakness 33 HP:0002460
9 distal amyotrophy 33 HP:0003693
10 segmental peripheral demyelination/remyelination 33 HP:0003481
11 distal sensory impairment 33 HP:0002936
12 axonal loss 33 HP:0003447
13 talipes cavus equinovarus 33 HP:0004696
14 onion bulb formation 33 HP:0003383
15 abnormal auditory evoked potentials 33 HP:0006958
16 intraaxonal accumulation of curvilinear autofluorescent lipopigment storage material 33 HP:0006916

Symptoms via clinical synopsis from OMIM:

58
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

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 30 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
A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom. ( 27982524 )
2017
2
Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D. ( 28776325 )
2017
3
Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D. ( 24136616 )
2014
4
CMT4D (NDRG1 mutation): genotype-phenotype correlations. ( 24028195 )
2013
5
The stretcher spontaneous neurodegenerative mutation models Charcot-Marie-Tooth disease type 4D. ( 24715951 )
2013
6
NDRG1-linked Charcot-Marie-Tooth disease (CMT4D) with central nervous system involvement. ( 17142040 )
2007
7
The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4. ( 17470135 )
2007
8
Mutation history of the roma/gypsies. ( 15322984 )
2004
9
Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease. ( 12872253 )
2003
10
N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. ( 10831399 )
2000

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 NG_007943.1: g.(43089_43830)_(47717_51712)dup duplication Pathogenic GRCh37 Chromosome 8, 134262787: 134271410
2 NDRG1 NG_007943.1: g.(43089_43830)_(47717_51712)dup duplication Pathogenic GRCh38 Chromosome 8, 133250544: 133259167
3 NDRG1 NM_006096.3(NDRG1): c.538-1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 8, 134266839: 134266839
4 NDRG1 NM_006096.3(NDRG1): c.538-1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 8, 133254596: 133254596
5 NDRG1 NM_001135242.1(NDRG1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs119483085 GRCh38 Chromosome 8, 133258374: 133258374
6 NDRG1 NM_001135242.1(NDRG1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs119483085 GRCh37 Chromosome 8, 134270617: 134270617
7 NDRG1 NC_000008.10: g.134265065_134271319dup duplication Pathogenic GRCh37 Chromosome 8, 134265065: 134271319
8 NDRG1 NM_006096.3(NDRG1): c.64-6T> C single nucleotide variant Benign rs2272653 GRCh38 Chromosome 8, 133280273: 133280273
9 NDRG1 NM_006096.3(NDRG1): c.64-6T> C single nucleotide variant Benign rs2272653 GRCh37 Chromosome 8, 134292516: 134292516

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 11.52 NDRG1 NDRG4
2 11.12 NDRG1 NDRG4
3 11.07 MYCN NDRG1 NDRG4
4 10.91 NDRG1 NDRG4

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

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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