CMT2DD
MCID: CHR678
MIFTS: 34

Charcot-Marie-Tooth Disease, Axonal, Type 2dd (CMT2DD)

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

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

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

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2dd 56 12 73 29 6 39
Cmt2dd 56 12 58 73
Charcot-Marie-Tooth Neuropathy, Type 2dd 56 12 73
Atp1a1-Related Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 12 58
Charcot-Marie-Tooth Disease Type 2dd 12 15
Atp1a1-Related Cmt2 12 58
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2dd 58
Charcot-Marie-Tooth Disease 2dd 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
lower limbs more affected than upper limbs
most patients remain ambulatory
some patients have upper limb involvement
variable age at onset (range late childhood to fifties)
most patients have onset in teens or twenties
some patients may have a subclinical course with minimal neurologic findings


HPO:

31
charcot-marie-tooth disease, axonal, type 2dd:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0111558
OMIM 56 618036
OMIM Phenotypic Series 56 PS118220
MeSH 43 D002607
Orphanet 58 ORPHA521414

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

OMIM : 56 Charcot-Marie-Tooth disease type 2DD is an autosomal dominant peripheral sensorimotor neuropathy mainly affecting the lower limbs. Affected individuals have gait impairment due to distal muscle weakness and atrophy. Some patients may also have involvement of the distal upper limbs, resulting in atrophy of the intrinsic hand muscles. The age at onset and severity of the disorder is highly variable, even within families, and those with earlier onset in late childhood or the teenage years tend to have a more severe disease course. Patients remain ambulatory even late in the disease, although some may require orthotic devices (summary by Lassuthova et al., 2018). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210). (618036)

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2dd, also known as cmt2dd, is related to parastremmatic dwarfism and hyperaldosteronism, familial, type i. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2dd is ATP1A1 (ATPase Na+/K+ Transporting Subunit Alpha 1), and among its related pathways/superpathways are Neuropathic Pain-Signaling in Dorsal Horn Neurons and cGMP-PKG signaling pathway. Related phenotypes are areflexia and pes cavus

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 characterized by neuropathy mainly affecting the lower limbs that has material basis in heterozygous mutation in ATP1A1 on chromosome 1p13.1.

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 2DD: A dominant 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.

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

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 2dd via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 parastremmatic dwarfism 9.7 ATP1A4 ATP1A1
2 hyperaldosteronism, familial, type i 9.7 ATP1A4 ATP1A1
3 adrenal gland disease 9.6 ATP1A4 ATP1A1
4 alternating hemiplegia of childhood 9.5 ATP1A4 ATP1A1
5 hypomagnesemia, seizures, and mental retardation 2 9.5 ATP1A1-AS1 ATP1A1
6 conn's syndrome 9.4 ATP1A4 ATP1A1

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



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

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

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

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 areflexia 31 HP:0001284
2 pes cavus 31 HP:0001761
3 hyporeflexia 31 HP:0001265
4 steppage gait 31 HP:0003376
5 muscle spasm 31 HP:0003394
6 foot dorsiflexor weakness 31 HP:0009027
7 sensorimotor neuropathy 31 HP:0007141

Symptoms via clinical synopsis from OMIM:

56
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
steppage gait
foot drop
sensorimotor peripheral neuropathy
more
Muscle Soft Tissue:
muscle cramps
distal muscle atrophy due to peripheral neuropathy
distal muscle weakness due to peripheral neuropathy

Skeletal Feet:
pes cavus

Skeletal Hands:
atrophy of the intrinsic hand muscles

Clinical features from OMIM:

618036

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2dd according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-100 9.17 ATP1A4
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.17 ATP1A4
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.17 ATP1A4
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 9.17 ATP1A1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-130 9.17 ATP1A4
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.17 ATP1A4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-46 9.17 ATP1A4

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

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

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Axonal, Type 2dd 29 ATP1A1

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

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

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

# Title Authors PMID Year
1
Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. 6 56
29499166 2018
2
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
3
Hereditary spastic paraplegia is a novel phenotype for germline de novo ATP1A1 mutation. 61
31705535 2020

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

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATP1A1 NM_000701.8(ATP1A1):c.143T>G (p.Leu48Arg)SNV Pathogenic 545677 rs1553190285 1:116927424-116927424 1:116384802-116384802
2 ATP1A1 NM_000701.8(ATP1A1):c.1798C>G (p.Pro600Ala)SNV Pathogenic 545678 rs1553192091 1:116937869-116937869 1:116395247-116395247
3 ATP1A1 NM_000701.8(ATP1A1):c.1798C>A (p.Pro600Thr)SNV Pathogenic 545679 rs1553192091 1:116937869-116937869 1:116395247-116395247
4 ATP1A1 NM_000701.8(ATP1A1):c.1775T>C (p.Ile592Thr)SNV Pathogenic 545680 rs1553192086 1:116937846-116937846 1:116395224-116395224
5 ATP1A1 NM_000701.8(ATP1A1):c.2432A>C (p.Asp811Ala)SNV Pathogenic 545681 rs1553192783 1:116941690-116941690 1:116399068-116399068

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2dd:

73
# Symbol AA change Variation ID SNP ID
1 ATP1A1 p.Leu48Arg VAR_081039 rs155319028
2 ATP1A1 p.Pro600Ala VAR_081042 rs155319209
3 ATP1A1 p.Asp811Ala VAR_081045 rs155319278

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

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

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

Pathways related to Charcot-Marie-Tooth Disease, Axonal, Type 2dd according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.14 ATP1A4 ATP1A1
2
Show member pathways
12.04 ATP1A4 ATP1A1
3
Show member pathways
12.02 ATP1A4 ATP1A1
4 11.84 ATP1A4 ATP1A1
5
Show member pathways
11.72 ATP1A4 ATP1A1
6
Show member pathways
11.57 ATP1A4 ATP1A1
7 11.54 ATP1A4 ATP1A1
8 11.44 ATP1A4 ATP1A1
9 11.36 ATP1A4 ATP1A1
10 11.31 ATP1A4 ATP1A1
11 11.09 ATP1A4 ATP1A1
12 10.98 ATP1A4 ATP1A1
13 10.83 ATP1A4 ATP1A1
14 10.52 ATP1A4 ATP1A1
15 9.98 ATP1A4 ATP1A1

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

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

# Name GO ID Score Top Affiliating Genes
1 membrane raft GO:0045121 8.96 ATP1A4 ATP1A1
2 sodium:potassium-exchanging ATPase complex GO:0005890 8.62 ATP1A4 ATP1A1

Biological processes related to Charcot-Marie-Tooth Disease, Axonal, Type 2dd according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.48 ATP1A4 ATP1A1
2 potassium ion transport GO:0006813 9.46 ATP1A4 ATP1A1
3 sodium ion transport GO:0006814 9.43 ATP1A4 ATP1A1
4 proton transmembrane transport GO:1902600 9.4 ATP1A4 ATP1A1
5 regulation of cardiac conduction GO:1903779 9.37 ATP1A4 ATP1A1
6 potassium ion import across plasma membrane GO:1990573 9.32 ATP1A4 ATP1A1
7 cellular sodium ion homeostasis GO:0006883 9.26 ATP1A4 ATP1A1
8 sodium ion export across plasma membrane GO:0036376 9.16 ATP1A4 ATP1A1
9 cellular potassium ion homeostasis GO:0030007 8.96 ATP1A4 ATP1A1
10 establishment or maintenance of transmembrane electrochemical gradient GO:0010248 8.62 ATP1A4 ATP1A1

Molecular functions related to Charcot-Marie-Tooth Disease, Axonal, Type 2dd according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sodium:potassium-exchanging ATPase activity GO:0005391 8.96 ATP1A4 ATP1A1
2 potassium-transporting ATPase activity GO:0008556 8.62 ATP1A4 ATP1A1

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....