CMT4F
MCID: CHR670
MIFTS: 40

Charcot-Marie-Tooth Disease, Demyelinating, Type 4f (CMT4F)

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

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

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

Name: Charcot-Marie-Tooth Disease, Demyelinating, Type 4f 56 29 6 71
Charcot-Marie-Tooth Disease Type 4f 12 52 58 15
Cmt4f 56 12 58 73
Charcot-Marie-Tooth Disease, Type 4f 56 13 39
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4f 73
Charcot-Marie-Tooth Neuropathy Type 4f 73
Charcot-Marie-Tooth Disease 4f 73
Dejerine-Sottas Disease 71

Characteristics:

Orphanet epidemiological data:

58
charcot-marie-tooth disease type 4f
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
distal upper limb involvement may occur later
variable age at onset (range from early childhood to mid-adult)


HPO:

31
charcot-marie-tooth disease, demyelinating, type 4f:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110193
OMIM 56 614895
OMIM Phenotypic Series 56 PS118220
ICD10 32 G60.0
ICD10 via Orphanet 33 G60.0
Orphanet 58 ORPHA99952
UMLS 71 C0011195 C3540453

Summaries for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 4F: 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. CMT4F is characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome.

MalaCards based summary : Charcot-Marie-Tooth Disease, Demyelinating, Type 4f, also known as charcot-marie-tooth disease type 4f, is related to hypertrophic neuropathy of dejerine-sottas and neuropathy, congenital hypomyelinating, 1, autosomal recessive, and has symptoms including ataxia, sensory An important gene associated with Charcot-Marie-Tooth Disease, Demyelinating, Type 4f is PRX (Periaxin). Affiliated tissues include skeletal muscle, and related phenotypes are vocal cord paresis and sensory ataxia

OMIM : 56 Charcot-Marie-Tooth disease type 4F is an autosomal recessive demyelinating neuropathy characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. Nerve conduction velocities are decreased and sural nerve biopsy shows loss of myelinated fibers. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome (DSS; 145900). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400). (614895)

Related Diseases for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Diseases in the Charcot-Marie-Tooth Disease, Demyelinating, Type 1b family:

Charcot-Marie-Tooth Disease, Demyelinating, Type 1a Charcot-Marie-Tooth Disease, Demyelinating, Type 1c
Charcot-Marie-Tooth Disease, Demyelinating, Type 1d Charcot-Marie-Tooth Disease, Demyelinating, Type 1f
Charcot-Marie-Tooth Disease, Demyelinating, Type 4f Charcot-Marie-Tooth Disease, Demyelinating, Type 1g

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

(show top 50) (show all 74)
# Related Disease Score Top Affiliating Genes
1 hypertrophic neuropathy of dejerine-sottas 29.2 SH3TC2 SBF2 PRX MTMR2 MPZ LITAF
2 neuropathy, congenital hypomyelinating, 1, autosomal recessive 27.7 SH3TC2 SBF2 PRX MTMR2 MPZ LITAF
3 neuropathy 27.6 SH3TC2 SBF2 PRX MTMR2 MPZ GJB1
4 peripheral nervous system disease 26.9 SH3TC2 SBF2 PRX MTMR2 MPZ LITAF
5 tooth disease 26.3 SH3TC2 SBF2 PRX MTMR2 MPZ LITAF
6 charcot-marie-tooth disease 25.7 SH3TC2 SBF2 PRX PLD3 MTMR2 MPZ
7 spinocerebellar ataxia 46 10.4 PRX PLD3
8 early-onset glaucoma 10.3 SBF2 MTMR2
9 argyll robertson pupil 10.2 MPZ GDAP1
10 pupil disease 10.2 MPZ GDAP1
11 charcot-marie-tooth disease, axonal, type 2a1 10.1 MPZ GDAP1
12 strabismus 10.1
13 scoliosis 10.1
14 myopia 10.1
15 progressive muscular atrophy 10.1
16 muscular atrophy 10.1
17 mechanical strabismus 10.1
18 infantile scoliosis 10.1
19 charcot-marie-tooth disease, axonal, type 2l 10.1 MPZ GDAP1
20 charcot-marie-tooth disease, axonal, type 2b2 10.1 MPZ GDAP1
21 charcot-marie-tooth disease, dominant intermediate c 10.0 MPZ GDAP1
22 charcot-marie-tooth disease x-linked recessive 4 9.9 MPZ GJB1
23 autoimmune peripheral neuropathy 9.9 MPZ GJB1
24 yunis-varon syndrome 9.9 SBF2 MTMR2 FIG4
25 abnormal pupillary function 9.9 MPZ GDAP1 EGR2
26 corneal dystrophy, fleck 9.9 SBF2 MTMR2 FIG4
27 mononeuropathy 9.9 SH3TC2 MPZ
28 neuropathy, hereditary motor and sensory, russe type 9.9 SH3TC2 GDAP1 EGR2
29 nerve compression syndrome 9.8 SH3TC2 MPZ
30 charcot-marie-tooth disease, type 4b3 9.8 SH3TC2 SBF2 MTMR2 GDAP1
31 charcot-marie-tooth disease, axonal, type 2cc 9.8 MPZ GJB1
32 charcot-marie-tooth disease, axonal, type 2d 9.8 MPZ GJB1 GDAP1
33 neuropathy, hereditary sensory and autonomic, type ic 9.8 SH3TC2 LITAF
34 charcot-marie-tooth disease, axonal, type 2p 9.8 LITAF GDAP1
35 charcot-marie-tooth disease, type 4k 9.7 SH3TC2 LITAF
36 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.7 MPZ GJB1 EGR2
37 charcot-marie-tooth disease, axonal, type 2q 9.7 MPZ GJB1 EGR2
38 hereditary neuropathies 9.6 PRX MTMR2 MPZ GJB1
39 charcot-marie-tooth disease, dominant intermediate a 9.6 PRX MPZ GJB1 GDAP1
40 charcot-marie-tooth disease, axonal, type 2f 9.6 MTMR2 MPZ GJB1 GDAP1
41 hereditary sensory and autonomic neuropathy type 1 9.6 SH3TC2 LITAF GDAP1
42 charcot-marie-tooth disease, dominant intermediate e 9.5 SH3TC2 SBF2 MTMR2 MPZ GDAP1
43 waardenburg syndrome, type 4a 9.5 MPZ GJB1
44 hereditary motor and sensory neuropathy, type iic 9.5 SH3TC2 MPZ GJB1 GDAP1
45 neuropathy, hereditary sensory and autonomic, type iia 9.3 SH3TC2 LITAF GDAP1 FGD4
46 charcot-marie-tooth disease, axonal, type 2j 9.2 SH3TC2 SBF2 MTMR2 MPZ GDAP1 EGR2
47 motor peripheral neuropathy 9.1 SH3TC2 LITAF GJB1 GDAP1
48 charcot-marie-tooth disease, x-linked recessive, 2 9.1 MPZ LITAF GJB1 EGR2
49 charcot-marie-tooth disease type x 8.9 SH3TC2 MTMR2 MPZ GJB1 GDAP1 EGR2
50 charcot-marie-tooth disease type 2a2a 8.9 SH3TC2 MPZ LITAF GJB1 GDAP1

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



Diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

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

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 vocal cord paresis 31 occasional (7.5%) HP:0001604
2 sensory ataxia 31 occasional (7.5%) HP:0010871
3 scoliosis 31 HP:0002650
4 skeletal muscle atrophy 31 HP:0003202
5 areflexia 31 HP:0001284
6 pes cavus 31 HP:0001761
7 decreased motor nerve conduction velocity 31 HP:0003431
8 motor delay 31 HP:0001270
9 difficulty walking 31 HP:0002355
10 limb muscle weakness 31 HP:0003690
11 peripheral demyelination 31 HP:0011096
12 distal sensory impairment 31 HP:0002936
13 decreased number of large peripheral myelinated nerve fibers 31 HP:0003387
14 basal lamina onion bulb formation 31 HP:0003400

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Skeletal Feet:
pes cavus

Voice:
vocal cord paresis (reported in 1 patient)

Neurologic Peripheral Nervous System:
areflexia
difficulty walking
distal sensory impairment
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)
loss of large myelinated fibers
more
Neurologic Central Nervous System:
delayed motor development
sensory ataxia (less common)

Clinical features from OMIM:

614895

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


ataxia, sensory

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 EGR2 FGD4 FIG4 GDAP1 GJB1 MPZ
2 nervous system MP:0003631 9.4 DRP2 EGR2 FGD4 FIG4 GDAP1 GJB1

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

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

Genetic Tests for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Demyelinating, Type 4f 29 PRX

Anatomical Context for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

40
Skeletal Muscle

Publications for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

(show all 26)
# Title Authors PMID Year
1
Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation. 61 56 6
22847150 2012
2
Charcot-Marie-Tooth type 4F disease caused by S399fsx410 mutation in the PRX gene. 61 56 6
16534116 2006
3
A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease. 61 56 6
11157804 2001
4
Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13.1-13.3 in a large consanguineous Lebanese family: exclusion of MAG as a candidate gene. 61 56 6
10848494 2000
5
Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease. 56 6
15197604 2004
6
Periaxin mutations cause a broad spectrum of demyelinating neuropathies. 56 6
12112076 2002
7
Four novel cases of periaxin-related neuropathy and review of the literature. 61 56
21079185 2010
8
Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease. 6
16770524 2006
9
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
10
Linkage analysis and whole exome sequencing reveals AHNAK2 as a novel genetic cause for autosomal recessive CMT in a Malaysian family. 61
31011849 2019
11
A Case Report on Charcot-Marie-Tooth Disease with a Novel Periaxin Gene Mutation. 61
31523542 2019
12
Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F. 61
31024253 2019
13
A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands. 61
29623298 2018
14
[Establishment of L-periaxin gene knock-out RSC96 cell line]. 61
29034641 2016
15
New mutation in periaxin gene causing Charcot Marie Tooth disease in a Puerto Rican young male. 61
24263033 2013
16
[Charcot-Marie-Tooth disease associated with periaxin mutations (CMT4F): Clinical, electrophysiological and genetic analysis of 24 patients]. 61
24011642 2013
17
Novel mutations in the PRX and the MTMR2 genes are responsible for unusual Charcot-Marie-Tooth disease phenotypes. 61
21741241 2011
18
Genetic study of demyelinating form of autosomal-recessive Charcot-Marie-tooth diseases in a Turkish family. 61
19922348 2009
19
Remodeling of motor nerve terminals in demyelinating axons of periaxin-null mice. 61
18205176 2008
20
[Molecular genetics of inherited neuropathies]. 61
17432174 2006
21
[Molecular genetics of inherited neuropathies]. 61
16541790 2006
22
Neuropathology of Charcot-Marie-Tooth and related disorders. 61
16775365 2006
23
The function of the Periaxin gene during nerve repair in a model of CMT4F. 61
12090399 2002
24
Neuropathology of some hereditary conditions affecting central and peripheral nervous system. 61
12094560 2002
25
A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13.3. 61
11112660 2001
26
Charcot-Marie-Tooth Neuropathy Type 4 61
20301641 1998

Variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

6 (show all 26) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PRX NM_181882.3(PRX):c.2787del (p.Lys930fs)deletion Pathogenic 217239 rs754521978 19:40901472-40901472 19:40395565-40395565
2 PRX NM_181882.3(PRX):c.2857C>T (p.Arg953Ter)SNV Pathogenic 4787 rs104894714 19:40901402-40901402 19:40395495-40395495
3 PRX NM_020956.2(PRX):c.*2350T>ASNV Pathogenic 4792 rs104894707 19:40902114-40902114 19:40396207-40396207
4 PRX NM_020956.2(PRX):c.*3413C>TSNV Pathogenic 4794 rs104894708 19:40901051-40901051 19:40395144-40395144
5 PRX NM_020956.2(PRX):c.*3908G>TSNV Pathogenic 549686 rs1385904344 19:40900556-40900556 19:40394649-40394649
6 PRX NM_020956.2(PRX):c.*1184deldeletion Pathogenic 634532 rs1568708792 19:40903280-40903280 19:40397373-40397373
7 PRX NM_181882.3(PRX):c.3085A>T (p.Arg1029Ter)SNV Likely pathogenic 800938 19:40901174-40901174 19:40395267-40395267
8 PRX NM_020956.2(PRX):c.*2494deldeletion Likely pathogenic 208606 rs797045102 19:40901970-40901970 19:40396063-40396063
9 PRX NM_020956.2(PRX):c.*1421G>ASNV Conflicting interpretations of pathogenicity 220724 rs117336941 19:40903043-40903043 19:40397136-40397136
10 PRX NM_020956.2(PRX):c.*791C>TSNV Conflicting interpretations of pathogenicity 4791 rs104894706 19:40903673-40903673 19:40397766-40397766
11 PRX NM_020956.2(PRX):c.*2303deldeletion Conflicting interpretations of pathogenicity 38453 rs281865062 19:40902161-40902161 19:40396254-40396254
12 PRX NM_020956.2(PRX):c.247del (p.Leu83fs)deletion Conflicting interpretations of pathogenicity 38454 rs281865061 19:40904661-40904661 19:40398754-40398754
13 PRX NM_020956.2(PRX):c.*1399_*1402deldeletion Conflicting interpretations of pathogenicity 637393 19:40903062-40903065 19:40397155-40397158
14 PRX NM_020956.2(PRX):c.*590_*599dupduplication Conflicting interpretations of pathogenicity 637915 19:40903864-40903865 19:40397957-40397958
15 PRX NM_020956.2(PRX):c.*4523G>ASNV Uncertain significance 634531 rs138437458 19:40899941-40899941 19:40394034-40394034
16 PRX NM_020956.2(PRX):c.*3974G>ASNV Uncertain significance 245824 rs200332462 19:40900490-40900490 19:40394583-40394583
17 PRX NM_020956.2(PRX):c.*1751C>TSNV Uncertain significance 246316 rs144305922 19:40902713-40902713 19:40396806-40396806
18 PRX NM_020956.2(PRX):c.*1688_*1765deldeletion Uncertain significance 410606 rs1555801137 19:40902699-40902776 19:40396792-40396869
19 PRX NM_020956.2(PRX):c.80C>A (p.Thr27Asn)SNV Uncertain significance 547996 rs1291881750 19:40909717-40909717 19:40403810-40403810
20 PRX NM_020956.2(PRX):c.*2156G>ASNV Uncertain significance 38452 rs3814290 19:40902308-40902308 19:40396401-40396401
21 PRX NM_020956.2(PRX):c.306C>T (p.Thr102=)SNV Benign/Likely benign 130051 rs744389 19:40904602-40904602 19:40398695-40398695
22 PRX NM_020956.2(PRX):c.*3453C>GSNV Benign/Likely benign 130052 rs3745202 19:40901011-40901011 19:40395104-40395104
23 PLD3 , PRX NM_020956.2(PRX):c.*4264_*4266GGA[6]short repeat Benign 215547 rs139624657 19:40900180-40900182 19:40394273-40394275
24 PRX NM_020956.2(PRX):c.*1688G>CSNV Benign 215545 rs146789340 19:40902776-40902776 19:40396869-40396869
25 PRX NM_020956.2(PRX):c.*2860T>CSNV Benign 130049 rs268672 19:40901604-40901604 19:40395697-40395697
26 PRX NM_020956.2(PRX):c.*2968A>GSNV Benign 130050 rs268673 19:40901496-40901496 19:40395589-40395589

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

73
# Symbol AA change Variation ID SNP ID
1 PRX p.Asp651Asn VAR_069093 rs3814290

Expression for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

Pathways for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

GO Terms for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

# Name GO ID Score Top Affiliating Genes
1 vacuolar membrane GO:0005774 9.16 SBF2 MTMR2
2 early endosome membrane GO:0031901 9.13 MTMR2 LITAF FIG4
3 endosome membrane GO:0010008 8.92 SBF2 MTMR2 LITAF FIG4

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

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol metabolic process GO:0046488 9.26 MTMR2 FIG4
2 negative regulation of myelination GO:0031642 9.16 MTMR2 FIG4
3 myelin assembly GO:0032288 8.96 MTMR2 FIG4
4 myelination GO:0042552 8.8 SBF2 MPZ EGR2

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

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-3-phosphatase activity GO:0004438 8.62 MTMR2 FIG4

Sources for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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