CMT2CC
MCID: CHR618
MIFTS: 29

Charcot-Marie-Tooth Disease, Axonal, Type 2cc (CMT2CC)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Axonal, Type 2cc:

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2cc 57 72 29 6
Cmt2cc 57 12 72
Charcot-Marie-Tooth Disease Axonal Type 2cc 12 15
Charcot-Marie-Tooth Neuropathy, Type 2cc 57 72
Charcot-Marie-Tooth Neuropathy Type 2cc 12
Charcot-Marie-Tooth Disease 2cc 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
progressive disorder
two unrelated families have been reported (last curated april 2016)
variable age at onset (range early childhood to fourth decade)


HPO:

31
charcot-marie-tooth disease, axonal, type 2cc:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity progressive


Classifications:



Summaries for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

UniProtKB/Swiss-Prot : 72 Charcot-Marie-Tooth disease 2CC: An axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2cc, also known as cmt2cc, is related to neuropathy and giant axonal neuropathy. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2cc is NEFH (Neurofilament Heavy Chain). Related phenotypes are proximal muscle weakness and elevated serum creatine kinase

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 that has material basis in heterozygous mutation in the NEFH gene on chromosome 22q12.

OMIM® : 57 Axonal Charcot-Marie-Tooth disease type 2CC is an autosomal dominant peripheral neuropathy that predominantly affects the lower limbs, resulting in muscle weakness and atrophy and gait impairment. Other features include distal sensory impairment and less severe involvement of the upper limbs. The age at onset and severity are variable (summary by Rebelo et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210). (616924) (Updated 20-May-2021)

Related Diseases for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Diseases in the Charcot-Marie-Tooth Disease, Axonal, Type 2e family:

Charcot-Marie-Tooth Disease, Axonal, Type 2a1 Charcot-Marie-Tooth Disease, Axonal, Type 2b
Charcot-Marie-Tooth Disease, Axonal, Type 2d Charcot-Marie-Tooth Disease, Axonal, Type 2b1
Charcot-Marie-Tooth Disease, Axonal, Type 2b2 Charcot-Marie-Tooth Disease, Axonal, Type 2f
Charcot-Marie-Tooth Disease, Axonal, Type 2i Charcot-Marie-Tooth Disease, Axonal, Type 2h
Charcot-Marie-Tooth Disease, Axonal, Type 2j Charcot-Marie-Tooth Disease, Axonal, Type 2k
Charcot-Marie-Tooth Disease, Axonal, Type 2l Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a
Charcot-Marie-Tooth Disease, Axonal, Type 2n Charcot-Marie-Tooth Disease, Axonal, Type 2o
Charcot-Marie-Tooth Disease, Axonal, Type 2p Charcot-Marie-Tooth Disease, Axonal, Type 2q
Charcot-Marie-Tooth Disease, Axonal, Type 2r Charcot-Marie-Tooth Disease, Axonal, Type 2u
Charcot-Marie-Tooth Disease, Axonal, Type 2v Charcot-Marie-Tooth Disease, Axonal, Type 2w
Charcot-Marie-Tooth Disease, Axonal, Type 2x Charcot-Marie-Tooth Disease, Axonal, Type 2z
Charcot-Marie-Tooth Disease, Axonal, Type 2cc Charcot-Marie-Tooth Disease, Axonal, Type 2t
Charcot-Marie-Tooth Disease, Axonal, Autosomal Recessive, Type 2a2b Charcot-Marie-Tooth Disease, Axonal, Type 2dd
Charcot-Marie-Tooth Disease, Axonal, Type 2ee Autosomal Recessive Axonal Charcot-Marie-Tooth Disease Due to Copper Metabolism Defect

Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 neuropathy 29.4 NEFH GAN DCAF8 APTX
2 giant axonal neuropathy 9.9 GAN DCAF8
3 charcot-marie-tooth disease, demyelinating, type 1f 9.9 NEFH DCAF8
4 ataxia-oculomotor apraxia 3 9.7 GAN APTX
5 charcot-marie-tooth disease 9.7 NEFH GAN DCAF8
6 giant axonal neuropathy 2 9.7 NEFH GAN DCAF8
7 axonal neuropathy 9.7 NEFH GAN DCAF8
8 motor peripheral neuropathy 9.6 DCAF8 APTX
9 neuropathy, congenital hypomyelinating, 1, autosomal recessive 9.6 GAN DCAF8
10 neuromuscular disease 9.6 NEFH GAN DCAF8
11 charcot-marie-tooth disease, axonal, type 2e 9.6 NEFH GAN DCAF8
12 peripheral nervous system disease 9.2 NEFH GAN DCAF8 APTX
13 disease of mental health 9.0 NEFH GAN DCAF8 APTX

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc:



Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Human phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 proximal muscle weakness 31 occasional (7.5%) HP:0003701
2 elevated serum creatine kinase 31 very rare (1%) HP:0003236
3 impaired vibratory sensation 31 very rare (1%) HP:0002495
4 babinski sign 31 very rare (1%) HP:0003487
5 upper limb muscle weakness 31 very rare (1%) HP:0003484
6 lower limb muscle weakness 31 very rare (1%) HP:0007340
7 lower limb amyotrophy 31 very rare (1%) HP:0007210
8 emg: neuropathic changes 31 very rare (1%) HP:0003445
9 upper limb amyotrophy 31 very rare (1%) HP:0009129
10 myopathy 31 HP:0003198
11 waddling gait 31 HP:0002515
12 rimmed vacuoles 31 HP:0003805
13 ragged-red muscle fibers 31 HP:0003200
14 pes cavus 31 HP:0001761
15 pyloric stenosis 31 HP:0002021
16 hyporeflexia 31 HP:0001265
17 frequent falls 31 HP:0002359
18 distal sensory impairment 31 HP:0002936
19 increased variability in muscle fiber diameter 31 HP:0003557
20 sensorimotor neuropathy 31 HP:0007141
21 muscle fiber splitting 31 HP:0003555
22 sensory axonal neuropathy 31 HP:0003390

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Feet:
pes cavus
high-arched feet

Neurologic Central Nervous System:
frequent falls
impaired gait due to peripheral neuropathy

Laboratory Abnormalities:
increase serum creatine kinase (in some patients)

Neurologic Peripheral Nervous System:
hyporeflexia
distal sensory impairment
axonal sensorimotor neuropathy
nerve conduction velocities are normal or slightly decreased
decreased amplitudes

Muscle Soft Tissue:
proximal muscle weakness (in some patients)
distal muscle weakness primarily in lower limbs due to peripheral neuropathy
distal muscle atrophy primarily in lower limbs due to peripheral neuropathy
neurogenic changes seen on emg and muscle biopsy
myopathic changes seen on emg and muscle biopsy (in some patients)

Clinical features from OMIM®:

616924 (Updated 20-May-2021)

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Genetic Tests for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Genetic tests related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Axonal, Type 2cc 29 NEFH

Anatomical Context for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Publications for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Articles related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc:

# Title Authors PMID Year
1
Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. 57 6
27040688 2016
2
A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC. 61
32780247 2021
3
Charcot-Marie-Tooth disease type 2CC due to a frameshift mutation of the neurofilament heavy polypeptide gene in an Austrian family. 61
30992180 2019
4
Axonal Charcot-Marie-Tooth neuropathy concurrent with distal and proximal weakness by translational elongation of the 3' UTR in NEFH. 61
28544463 2017
5
Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. 61
28709447 2017

Variations for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2cc:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NEFH NM_021076.4(NEFH):c.3017_3020dup (p.Pro1008fs) Duplication Pathogenic 225631 rs876657412 GRCh37: 22:29886645-29886646
GRCh38: 22:29490656-29490657
2 NEFH NM_021076.4(NEFH):c.3010_3011del (p.Asp1004fs) Deletion Pathogenic 225630 rs876657411 GRCh37: 22:29886638-29886639
GRCh38: 22:29490649-29490650
3 NEFH NM_021076.4(NEFH):c.2327C>G (p.Ser776Cys) SNV Uncertain significance 1033974 GRCh37: 22:29885956-29885956
GRCh38: 22:29489967-29489967
4 NEFH NM_021076.4(NEFH):c.25G>C (p.Ala9Pro) SNV Uncertain significance 1033975 GRCh37: 22:29876276-29876276
GRCh38: 22:29480287-29480287

Expression for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Axonal, Type 2cc.

Pathways for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

GO Terms for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

Cellular components related to Charcot-Marie-Tooth Disease, Axonal, Type 2cc according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.02 NEFH GAN DCAF8 APTX ACY1

Sources for Charcot-Marie-Tooth Disease, Axonal, Type 2cc

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....