CMTDIG
MCID: CHR676
MIFTS: 25

Charcot-Marie-Tooth Disease, Dominant Intermediate G (CMTDIG)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Dominant Intermediate G

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Dominant Intermediate G:

Name: Charcot-Marie-Tooth Disease, Dominant Intermediate G 56 73 29 6
Cmtdig 56 73
Charcot-Marie-Tooth Disease, Dominant, Intermediate Type, G 73
Charcot-Marie-Tooth Disease Dominant Intermediate G 12

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype
slowly progressive
later onset has been reported
onset usually in first or second decade


HPO:

31
charcot-marie-tooth disease, dominant intermediate g:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:



Summaries for Charcot-Marie-Tooth Disease, Dominant Intermediate G

OMIM : 56 CMTDIG is an autosomal dominant neurologic disorder with a highly variable phenotype. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment. More severely affected individuals may have pes cavus and claw hands and become wheelchair-bound, whereas other affected individuals have later onset with a milder disease course. Electrophysiologic studies tend to show median motor nerve conduction velocities (NCV) in the 'intermediate' range, between 25 and 45 m/s (summary by Berciano et al., 2017). In a review of intermediate CMT, Berciano et al. (2017) noted that advanced axonal degeneration may induce secondary demyelinating changes resulting in decreased NCV and attenuated compound muscle action potential (CMAP) in median nerve conduction studies. They thus suggested that testing the upper arm, axilla to elbow, may provide more accurate assessment of NCV and CMAP and reveal an intermediate phenotype (review by Berciano et al., 2017). For a discussion of genetic heterogeneity of CMTDI, see 606482. (617882)

MalaCards based summary : Charcot-Marie-Tooth Disease, Dominant Intermediate G, is also known as cmtdig. An important gene associated with Charcot-Marie-Tooth Disease, Dominant Intermediate G is NEFL (Neurofilament Light). Affiliated tissues include testes and eye, and related phenotypes are spasticity and ataxia

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease, dominant intermediate G: An autosomal dominant, intermediate 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. Dominant intermediate forms are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. CMTDIG is phenotypically variable. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment.

Related Diseases for Charcot-Marie-Tooth Disease, Dominant Intermediate G

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 D
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, Dominant Intermediate E
Charcot-Marie-Tooth Disease, Dominant Intermediate F Charcot-Marie-Tooth Disease, Type 4b3
Charcot-Marie-Tooth Disease, Recessive Intermediate C Charcot-Marie-Tooth Disease, Recessive Intermediate D
Charcot-Marie-Tooth Disease, Type 4k Charcot-Marie-Tooth Disease, Dominant Intermediate G
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 2a2a Charcot-Marie-Tooth Disease Type 2a2b
Charcot-Marie-Tooth Disease Type 1g Autosomal Dominant Intermediate Charcot-Marie-Tooth
Autosomal Recessive Intermediate Charcot-Marie-Tooth Disease Charcot-Marie-Tooth Disease Type 2a
Charcot-Marie-Tooth Disease Type 2l 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

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Human phenotypes related to Charcot-Marie-Tooth Disease, Dominant Intermediate G:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 very rare (1%) HP:0001257
2 ataxia 31 very rare (1%) HP:0001251
3 sensorineural hearing impairment 31 very rare (1%) HP:0000407
4 gowers sign 31 very rare (1%) HP:0003391
5 nystagmus 31 HP:0000639
6 areflexia 31 HP:0001284
7 babinski sign 31 HP:0003487
8 pes cavus 31 HP:0001761
9 waddling gait 31 HP:0002515
10 motor delay 31 HP:0001270
11 hyporeflexia 31 HP:0001265
12 split hand 31 HP:0001171
13 sensorimotor neuropathy 31 HP:0007141
14 distal muscle weakness 31 HP:0002460
15 steppage gait 31 HP:0003376
16 distal sensory impairment 31 HP:0002936
17 elevated serum creatine kinase 31 HP:0003236

Symptoms via clinical synopsis from OMIM:

56
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
loss of large myelinated fibers seen on sural nerve biopsy
sensorimotor neuropathy (upper and lower limbs affected)
more
Neurologic Central Nervous System:
waddling gait
steppage gait
delayed motor development
extensor plantar responses
impaired gait
more
Muscle Soft Tissue:
muscle weakness, distal
upper and lower limbs affected
proximal muscle weakness (in some patients)
gowers sign (in some patients)
amyotrophy, distal

Head And Neck Ears:
sensorineural hearing loss (in some patients)

Skeletal Feet:
pes cavus
pes calcaneovalgus

Laboratory Abnormalities:
increased serum creatine kinase

Skeletal Hands:
claw hands

Head And Neck Eyes:
nystagmus (uncommon)
impaired blink response (in some patients)
abnormal saccades (uncommon)

Clinical features from OMIM:

617882

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Genetic Tests for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Genetic tests related to Charcot-Marie-Tooth Disease, Dominant Intermediate G:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Dominant Intermediate G 29 NEFL

Anatomical Context for Charcot-Marie-Tooth Disease, Dominant Intermediate G

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Dominant Intermediate G:

40
Testes, Eye

Publications for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Articles related to Charcot-Marie-Tooth Disease, Dominant Intermediate G:

# Title Authors PMID Year
1
NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype. 56 6
26645395 2016
2
NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype. 56 6
25877835 2015
3
Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie- Tooth disease type 2E. 56 6
24887401 2014
4
Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton. 56 6
17052987 2007
5
The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy. 56 6
14733962 2004
6
Intermediate Charcot-Marie-Tooth disease: an electrophysiological reappraisal and systematic review. 56
28364294 2017
7
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
8
A novel pathogenic variant of NEFL responsible for deafness associated with peripheral neuropathy discovered through next-generation sequencing and review of the literature. 61
30734407 2019

Variations for Charcot-Marie-Tooth Disease, Dominant Intermediate G

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate G:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NEFL NM_006158.4(NEFL):c.293A>G (p.Asn98Ser)SNV Pathogenic 41236 rs58982919 8:24813737-24813737 8:24956223-24956223
2 NEFL NM_006158.4(NEFL):c.1186G>A (p.Glu396Lys)SNV Pathogenic 66671 rs62636503 8:24811293-24811293 8:24953779-24953779
3 NEFL NM_006158.4(NEFL):c.1610A>G (p.Gln537Arg)SNV Conflicting interpretations of pathogenicity 220209 rs377121179 8:24810345-24810345 8:24952832-24952832
4 NEFL NM_006158.4(NEFL):c.986T>C (p.Leu329Pro)SNV Uncertain significance 234913 rs876661290 8:24813044-24813044 8:24955530-24955530

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate G:

73
# Symbol AA change Variation ID SNP ID
1 NEFL p.Asn98Ser VAR_016023 rs58982919
2 NEFL p.Glu396Lys VAR_021614 rs62636503

Expression for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Dominant Intermediate G.

Pathways for Charcot-Marie-Tooth Disease, Dominant Intermediate G

GO Terms for Charcot-Marie-Tooth Disease, Dominant Intermediate G

Sources for Charcot-Marie-Tooth Disease, Dominant Intermediate G

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
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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
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