Charcot–Marie–Tooth disease classifications
Classifications of Charcot–Marie–Tooth disease refers to the types and subtypes of
muscle tissue and touch sensation across various parts of the body. CMT is a result of genetic mutations in a number of genes.[1]
Clinical categories
Type | Name | Incidence | Notes |
---|---|---|---|
CMT1 | Demyelinating type | Affects approximately 30% of CMT patients | Causes severe demyelination, thereby impairing nerve conduction velocity .
|
CMT2 | Axonal type | Affects approximately 20–40% of CMT patients | Mainly affects axonopathy, average nerve conduction velocity is usually not affected (sometimes slightly below normal but mostly above 38 m/s ).
|
CMT3 | Dejerine–Sottas disease | Very rare | Severely impaired nerve conduction velocity. |
CMT4 | Spinal type | ||
CMT5 | Pyramidal type | ||
CMT6 | With optic atrophy | ||
CMTDI | Dominant intermediate type | ||
CMTRI | Recessive intermediate type | ||
CMTX | X-linked type | Affects approximately 10–20% of CMT patients | This type encompasses all CMT forms that are inherited in an . |
Genetic subtypes
Type | Subtype | OMIM
|
Gene | Locus | Inheritance | Notes |
---|---|---|---|---|---|---|
CMT1 | CMT1A[2] | 118220 | PMP22 |
17p11.2 | Autosomal dominant |
The most common form of the disease, 70–80% of Type 1 patients. Average NCV: 20–25 m/s. Allelic with subtype CMT1E. When associated with subtype CMT1B (causing essential tremor and ataxia), it is called Roussy–Lévy syndrome. |
CMT1B | 118200 | MPZ | 1q23.3 | Autosomal dominant |
Responsible for 5–10% of Type 1 patients. Average NCV: < 15 m/s | |
CMT1C | 601098 | LITAF | 16p13.13 | Autosomal dominant |
Usually shows up in infancy. Average NCV: 26–42 m/s. Symptoms are identical to CMT1A. | |
CMT1D | 607678 | EGR2 | 10q21.3 | Autosomal dominant |
Average NCV: 15–20 m/s | |
CMT1E | 118300 | PMP22 |
17p11.2 | Autosomal dominant |
Characterised by demyelination and loss of hearing ; allelic with subtype CMT1A
| |
CMT1F | 607734 | NEFL |
8p21.2 | Autosomal dominant |
||
CMT1G | 618279 | PMP2 | 8q21.13 | Autosomal dominant |
||
CMT2 | CMT2A1 | 118210 | KIF1B | 1p36.22 | Autosomal dominant |
|
CMT2A2A | 609260 | MFN2 | 1p36.22 | Autosomal dominant |
||
CMT2A2B | 617087 | MFN2 | 1p36.22 | Autosomal recessive |
||
CMT2B | 600882 | RAB7A RAB7B |
3q21.3 | Autosomal dominant |
||
CMT2B1 | 605588 | LMNA |
1q22 | Autosomal recessive |
A laminopathy | |
CMT2B2 | 605589 | MED25 | 19q13.33 | Autosomal dominant |
||
CMT2C | 606071 | TRPV4 | 12q24.11 | Autosomal dominant |
May cause vocal cord, diaphragm, and distal weakness | |
CMT2D | 601472 | GARS |
7p14.3 | Autosomal dominant |
Symptoms are more severe in the upper extremities (hands), which is atypical for CMT | |
CMT2E | 607684 | NEFL |
8p21.2 | Autosomal dominant |
||
CMT2F | 606595 | HSPB1 |
7q11.23 | Autosomal dominant |
||
CMT2H | 607731 | GDAP1 | 8q21.11 | Autosomal dominant |
Allelic with subtype CMT2K | |
CMT2I | 607677 | MPZ | 1q23.3 | Autosomal dominant |
Allelic with subtype CMT2J and forms of CMT3 | |
CMT2J | 607736 | MPZ | 1q23.3 | Autosomal dominant |
Allelic with subtype CMT2I and forms of CMT3 | |
CMT2K | 607831 | GDAP1 | 8q21.11 | Autosomal dominant |
Allelic with subtype CMT2H | |
CMT2L | 608673 | HSPB8 | 12q24.23 | Autosomal dominant |
Allelic with Autosomal dominant distal spinal muscular atrophy | |
CMT2M | 606482 | DNM2 | 19p13.2 | Autosomal dominant |
Full name: CMT2M, included; more commonly classified as subtype CMTDIB | |
CMT2N | 613287 | AARS | 16q22.1 | Autosomal dominant |
||
CMT2O | 614228 | DYNC1H1 | 14q32.31 | Autosomal dominant |
Allelic with spinal muscular atrophy with lower extremity predominance 1 | |
CMT2P | 614436 | LRSAM1 | 9q33.3 | Autosomal recessive |
Juvenile or adult onset, slowly progressive | |
CMT2Q | 615025 | DHTKD1 | 10p14 | Autosomal dominant |
||
CMT2R | 615490 | TRIM2 | 4q31.3 | Autosomal recessive |
||
CMT2S | 616155 | IGHMBP2 | 11q13.3 | Autosomal recessive |
||
CMT2T | 617017 | MME |
3q25 | Autosomal recessive |
||
CMT2U | 616280 | MARS | 12q13.3 | Autosomal dominant |
||
CMT2V | 616491 | NAGLU | 17q21.2 | Autosomal dominant |
||
CMT2W | 616625 | HARS1 |
5q31.3 | Autosomal dominant |
||
CMT2X | 616668 | SPG11 | 15q21.1 | Autosomal recessive |
||
CMT2Y | 616687 | VCP |
9p13.3 | Autosomal dominant |
||
CMT2Z | 616688 | MORC2 | 22q12.2 | Autosomal dominant |
||
CMT2CC | 616924 | NEFH | 22q12.2 | Autosomal dominant |
||
CMT2DD | 618036 | ATP1A1 |
1p13.1 | Autosomal dominant |
||
CMT2EE | 618400 | MPV17 | 2p23.3 | Autosomal recessive |
||
CMT3 | CMT3 | 145900 | PMP22 PRX |
1q23.3 10q21.3 17p12 19q13.2 |
Autosomal recessive |
More commonly known as Dejerine–Sottas disease; subtype CMT4F sometimes included here |
CMT4 | CMT4A | 214400 | GDAP1 | 8q21.11 | Autosomal recessive |
Allelic with subtype CMTRIA |
CMT4B1 | 601382 | MTMR2 | 11q21 | Autosomal recessive |
||
CMT4B2 | 604563 | SBF2 | 11p15.4 | Autosomal recessive |
||
CMT4B3 | 615284 | SBF1 | 22q13.33 | Autosomal recessive |
||
CMT4C | 601596 | SH3TC2 | 5q32 | Autosomal recessive |
May lead to respiratory compromise | |
CMT4D | 601455 | NDRG1 | 8q24.3 | Autosomal recessive |
Characterised by demyelination and loss of hearing
| |
CMT4E | 605253 | MPZ EGR2 |
1q23.3 10q21.3 |
Autosomal recessive |
Also known as congenital hypomyelinating neuropathy; phenotype largely overlapping with subtype CMT4F | |
CMT4F | 145900 | PRX | 19q13.2 | Autosomal recessive |
Phenotype largely overlapping with subtype CMT4E; may be the same as CMT3 | |
CMT4G | 605285 | HK1 | 10q22.1 | Autosomal recessive |
Also known as Russe-type hereditary motor and sensory neuropathy (HMSNR); second most common cause of CMT in the Spanish Roma population | |
CMT4H | 609311 | FGD4 | 12p11.21 | Autosomal recessive |
||
CMT4J | 611228 | FIG4 |
6q21 | Autosomal recessive |
Allelic to amyotrophic lateral sclerosis type 11
| |
CMT5 | CMT5 | 600361 | ? | 4q34.3–q35.2 | Autosomal dominant |
Also known as CMT with pyramidal features; onset in 2nd decade of life with distal muscle wasting, particularly in legs |
CMT6 | CMT6A | 601152 | MFN2 | 1p36.22 | Autosomal dominant |
Characterised by optic atrophy, hence known also as CMT with optic atrophy. Also known as hereditary motor and sensory neuropathy type VI.
|
CMT6B | 616505 | SLC25A46 | 5q22.1 | Autosomal recessive
| ||
CMT6C | 618511 | PDXK | 21q22.3 | Autosomal recessive
| ||
CMTDI | CMTDIA | 606483 | ? | 10q24.1–q25.1 | Autosomal dominant |
|
CMTDIB | 606482 | DNM2 | 19p13.2 | Autosomal dominant |
Also classified as subtype CMT2M | |
CMTDIC | 608323 | YARS | 1p35.1 | Autosomal dominant |
||
CMTDID | 607791 | MPZ | 1q23.3 | Autosomal dominant |
||
CMTDIE | 614455 | INF2 | 14q32.33 | Autosomal dominant |
||
CMTDIF | 615185 | GNB4 | 3q26.33 | Autosomal dominant |
||
CMTRI | CMTRIA | 608340 | GDAP1 | 8q21.11 | Autosomal recessive |
Allelic with subtype CMT4A |
CMTRIB | 613641 | KARS | 16q23.1 | Autosomal recessive |
||
CMTX | CMTX1 | 302800 | GJB1 | Xq13.1 | X-linked dominant |
Responsible for approximately 90% of CMTX patients; some studies put this number significantly higher.[3][4] Note that different mutations of GJB1 may produce markedly different forms of Charcot–Marie–Tooth disease. |
CMTX2 | 302801 | CMTX2 | Xq22.2 | X-linked recessive |
||
CMTX3 | 302802 | CMTX3 | Xq26 | X-linked recessive |
||
CMTX4 | 310490 | NAMSD | Xq24–q26.1 | X-linked recessive |
Also known as Cowchock syndrome | |
CMTX5 | 311070 | PRPS1 |
Xq22.3 | X-linked recessive |
Also known as Rosenberg–Chutorian syndrome; signs include optic atrophy, polyneuropathy and deafness
| |
CMTX6 | 300905 | PDK3 | Xp22.11 | X-linked dominant |
||
Type | Subtype | OMIM
|
Gene | Locus | Inheritance | Notes |
It has to be kept in mind that sometimes a particular patient diagnosed with CMT can exhibit a combination of any of the above gene mutations; thus, in these cases precise classification can be arbitrary.
References
- PMID 20220177.
- PMID 11381029.
- PMID 9018031.
- ISBN 978-1-934115-46-6.