MCID: CHR421
MIFTS: 37

Charcot-Marie-Tooth Disease, Type 4h

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

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

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

Name: Charcot-Marie-Tooth Disease, Type 4h 57 53 29 13 6 40 73
Cmt4h 57 12 24 53 59 75
Charcot-Marie-Tooth Disease Type 4h 12 24 53 59 15
Charcot-Marie-Tooth Neuropathy Type 4h 12 24 75
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4h 57 53
Charcot-Marie-Tooth Disease, Autosomal Recessive, Type 4h 57 53
Charcot-Marie-Tooth Neuropathy, Type 4h 57 53
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4h 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4h 75
Autosomal Recessive Charcot-Marie-Tooth Disease Type 4h 12
Charcot-Marie-Tooth Disease 4h 75

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4h
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
usually begins in feet and legs (peroneal distribution)
onset before age 2 years
severe disorder
genetic heterogeneity (see cmt4a )


HPO:

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


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 609311
Disease Ontology 12 DOID:0110192
ICD10 33 G60.0
Orphanet 59 ORPHA99954
ICD10 via Orphanet 34 G60.0
UMLS via Orphanet 74 C1836336
MedGen 42 C1836336
MeSH 44 D002607
UMLS 73 C1836336

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

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease 4H: 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 4h, also known as cmt4h, is related to neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive and tooth disease, and has symptoms including waddling gait An important gene associated with Charcot-Marie-Tooth Disease, Type 4h is FGD4 (FYVE, RhoGEF And PH Domain Containing 4), and among its related pathways/superpathways are Signaling by Rho GTPases and p75 NTR receptor-mediated signalling. Related phenotypes are hyporeflexia and motor delay

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in mutations in the gene encoding frabin (FGD4).

Description from OMIM: 609311
GeneReviews: NBK153601

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

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

# Related Disease Score Top Affiliating Genes
1 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 11.1
2 tooth disease 10.7
3 charcot-marie-tooth disease 10.7
4 neuropathy 10.0

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

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
delayed motor development
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)
more
Skeletal Feet:
pes cavus
pes equinus


Clinical features from OMIM:

609311

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

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 hyporeflexia 32 HP:0001265
2 motor delay 32 HP:0001270
3 areflexia 32 HP:0001284
4 pes cavus 32 HP:0001761
5 talipes equinovarus 32 HP:0001762
6 waddling gait 32 HP:0002515
7 scoliosis 32 HP:0002650
8 distal sensory impairment 32 HP:0002936
9 decreased number of peripheral myelinated nerve fibers 32 HP:0003380
10 onion bulb formation 32 HP:0003383
11 decreased motor nerve conduction velocity 32 HP:0003431
12 upper limb muscle weakness 32 HP:0003484
13 distal lower limb amyotrophy 32 HP:0008944
14 distal lower limb muscle weakness 32 HP:0009053
15 peripheral demyelination 32 HP:0011096

UMLS symptoms related to Charcot-Marie-Tooth Disease, Type 4h:


waddling gait

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Type 4h according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 9.4 FGD4
2 Increased shRNA abundance (Z-score > 2) GR00366-A-103 9.4 FGD4
3 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.4 FGD4
4 Increased shRNA abundance (Z-score > 2) GR00366-A-125 9.4 FGD4
5 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.4 ARHGEF3 FGD4
6 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.4 FGD4
7 Increased shRNA abundance (Z-score > 2) GR00366-A-205 9.4 FGD4
8 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.4 ARHGEF3
9 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.4 ARHGEF3
10 Increased shRNA abundance (Z-score > 2) GR00366-A-56 9.4 FGD4
11 Increased shRNA abundance (Z-score > 2) GR00366-A-92 9.4 FGD4
12 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.96 ARHGEF3 CDC42

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

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

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4h 29 FGD4

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

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

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

# Title Authors Year
1
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. ( 28847448 )
2017
2
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. ( 26400421 )
2015
3
A Novel Mutation in FGD4/FRABIN Causes Charcot Marie Tooth Disease Type 4H in Patients from a Consanguineous Tunisian Family. ( 23550889 )
2013
4
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G&amp;gt;A mutation. ( 23770104 )
2013
5
Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. ( 19332693 )
2009

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

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

75
# Symbol AA change Variation ID SNP ID
1 FGD4 p.Met298Arg VAR_034957 rs63749871
2 FGD4 p.Met298Thr VAR_044321 rs63749871

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

6
(show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 FGD4 NM_139241.3(FGD4): c.670C> T (p.Arg224Ter) single nucleotide variant Pathogenic rs118203972 GRCh37 Chromosome 12, 32751500: 32751500
2 FGD4 NM_139241.3(FGD4): c.670C> T (p.Arg224Ter) single nucleotide variant Pathogenic rs118203972 GRCh38 Chromosome 12, 32598566: 32598566
3 FGD4 FGD4, 893T-G single nucleotide variant Pathogenic
4 FGD4 FGD4, 2-BP DEL, 1626AG deletion Pathogenic
5 FGD4 NM_139241.3(FGD4): c.1756G> T (p.Gly586Ter) single nucleotide variant Pathogenic rs118203973 GRCh37 Chromosome 12, 32778708: 32778708
6 FGD4 NM_139241.3(FGD4): c.1756G> T (p.Gly586Ter) single nucleotide variant Pathogenic rs118203973 GRCh38 Chromosome 12, 32625774: 32625774
7 FGD4 NM_139241.3(FGD4): c.893T> C (p.Met298Thr) single nucleotide variant Pathogenic rs63749871 GRCh37 Chromosome 12, 32755151: 32755151
8 FGD4 NM_139241.3(FGD4): c.893T> C (p.Met298Thr) single nucleotide variant Pathogenic rs63749871 GRCh38 Chromosome 12, 32602217: 32602217
9 FGD4 NM_139241.3(FGD4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs118203974 GRCh37 Chromosome 12, 32754344: 32754344
10 FGD4 NM_139241.3(FGD4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs118203974 GRCh38 Chromosome 12, 32601410: 32601410
11 FGD4 NM_139241.3(FGD4): c.1762-2A> G single nucleotide variant Pathogenic rs281865065 GRCh37 Chromosome 12, 32786481: 32786481
12 FGD4 NM_139241.3(FGD4): c.1762-2A> G single nucleotide variant Pathogenic rs281865065 GRCh38 Chromosome 12, 32633547: 32633547
13 FGD4 NM_139241.3(FGD4): c.1325G> A (p.Arg442His) single nucleotide variant Pathogenic rs281865063 GRCh37 Chromosome 12, 32764204: 32764204
14 FGD4 NM_139241.3(FGD4): c.1325G> A (p.Arg442His) single nucleotide variant Pathogenic rs281865063 GRCh38 Chromosome 12, 32611270: 32611270
15 FGD4 NM_139241.2(FGD4): c.1698G> H single nucleotide variant Pathogenic rs281865064 GRCh37 Chromosome 12, 32778650: 32778650
16 FGD4 NM_139241.2(FGD4): c.1698G> H single nucleotide variant Pathogenic rs281865064 GRCh38 Chromosome 12, 32625716: 32625716
17 FGD4 NM_139241.3(FGD4): c.893T> G (p.Met298Arg) single nucleotide variant Pathogenic rs63749871 GRCh37 Chromosome 12, 32755151: 32755151
18 FGD4 NM_139241.3(FGD4): c.893T> G (p.Met298Arg) single nucleotide variant Pathogenic rs63749871 GRCh38 Chromosome 12, 32602217: 32602217

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

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

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

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

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

# Name GO ID Score Top Affiliating Genes
1 filopodium GO:0030175 8.62 CDC42 FGD4

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.4 ARHGEF3 FGD4
2 regulation of molecular function GO:0065009 9.37 ARHGEF3 FGD4
3 actin cytoskeleton organization GO:0030036 9.32 CDC42 FGD4
4 regulation of cell shape GO:0008360 9.26 CDC42 FGD4
5 regulation of Rho protein signal transduction GO:0035023 9.16 ARHGEF3 FGD4
6 Rho protein signal transduction GO:0007266 8.96 ARHGEF3 CDC42
7 regulation of small GTPase mediated signal transduction GO:0051056 8.8 ARHGEF3 CDC42 FGD4

Molecular functions related to Charcot-Marie-Tooth Disease, Type 4h according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 8.96 ARHGEF3 FGD4
2 Rho guanyl-nucleotide exchange factor activity GO:0005089 8.62 ARHGEF3 FGD4

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

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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