Medicine:Charcot–Marie–Tooth disease classifications
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Classifications of Charcot–Marie–Tooth disease refers to the types and subtypes of Charcot–Marie–Tooth disease (CMT), a genetically and clinically heterogeneous group of inherited disorders of the peripheral nervous system characterized by progressive loss 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 axons. Tends to affect lower extremities more than upper extremities. Clinical symptoms are often less severe than in CMT1. As it is an 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 X-linked manner. Average NCV: 25–40 m/s. |
Genetic subtypes
Type | Subtype | OMIM | Gene | Locus | Inheritance | Notes |
---|---|---|---|---|---|---|
CMT1 | CMT1A[2] | Online Mendelian Inheritance in Man (OMIM) 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 | Online Mendelian Inheritance in Man (OMIM) 118200 | MPZ | 1q23.3 | Autosomal dominant | Responsible for 5–10% of Type 1 patients. Average NCV: < 15 m/s | |
CMT1C | Online Mendelian Inheritance in Man (OMIM) 601098 | LITAF | 16p13.13 | Autosomal dominant | Usually shows up in infancy. Average NCV: 26–42 m/s. Symptoms are identical to CMT1A. | |
CMT1D | Online Mendelian Inheritance in Man (OMIM) 607678 | EGR2 | 10q21.3 | Autosomal dominant | Average NCV: 15–20 m/s | |
CMT1E | Online Mendelian Inheritance in Man (OMIM) 118300 | PMP22 | 17p11.2 | Autosomal dominant | Characterised by demyelination and loss of hearing; allelic with subtype CMT1A | |
CMT1F | Online Mendelian Inheritance in Man (OMIM) 607734 | NEFL | 8p21.2 | Autosomal dominant | ||
CMT1G | Online Mendelian Inheritance in Man (OMIM) 618279 | PMP2 | 8q21.13 | Autosomal dominant | ||
CMT2 | CMT2A1 | Online Mendelian Inheritance in Man (OMIM) 118210 | KIF1B | 1p36.22 | Autosomal dominant | |
CMT2A2A | Online Mendelian Inheritance in Man (OMIM) 609260 | MFN2 | 1p36.22 | Autosomal dominant | ||
CMT2A2B | Online Mendelian Inheritance in Man (OMIM) 617087 | MFN2 | 1p36.22 | Autosomal recessive | ||
CMT2B | Online Mendelian Inheritance in Man (OMIM) 600882 | RAB7A RAB7B |
3q21.3 | Autosomal dominant | ||
CMT2B1 | Online Mendelian Inheritance in Man (OMIM) 605588 | LMNA | 1q22 | Autosomal recessive | A laminopathy | |
CMT2B2 | Online Mendelian Inheritance in Man (OMIM) 605589 | MED25 | 19q13.33 | Autosomal dominant | ||
CMT2C | Online Mendelian Inheritance in Man (OMIM) 606071 | TRPV4 | 12q24.11 | Autosomal dominant | May cause vocal cord, diaphragm, and distal weakness | |
CMT2D | Online Mendelian Inheritance in Man (OMIM) 601472 | GARS | 7p14.3 | Autosomal dominant | Symptoms are more severe in the upper extremities (hands), which is atypical for CMT | |
CMT2E | Online Mendelian Inheritance in Man (OMIM) 607684 | NEFL | 8p21.2 | Autosomal dominant | ||
CMT2F | Online Mendelian Inheritance in Man (OMIM) 606595 | HSPB1 | 7q11.23 | Autosomal dominant | ||
CMT2H | Online Mendelian Inheritance in Man (OMIM) 607731 | GDAP1 | 8q21.11 | Autosomal dominant | Allelic with subtype CMT2K | |
CMT2I | Online Mendelian Inheritance in Man (OMIM) 607677 | MPZ | 1q23.3 | Autosomal dominant | Allelic with subtype CMT2J and forms of CMT3 | |
CMT2J | Online Mendelian Inheritance in Man (OMIM) 607736 | MPZ | 1q23.3 | Autosomal dominant | Allelic with subtype CMT2I and forms of CMT3 | |
CMT2K | Online Mendelian Inheritance in Man (OMIM) 607831 | GDAP1 | 8q21.11 | Autosomal dominant | Allelic with subtype CMT2H | |
CMT2L | Online Mendelian Inheritance in Man (OMIM) 608673 | HSPB8 | 12q24.23 | Autosomal dominant | Allelic with Autosomal dominant distal spinal muscular atrophy | |
CMT2M | Online Mendelian Inheritance in Man (OMIM) 606482 | DNM2 | 19p13.2 | Autosomal dominant | Full name: CMT2M, included; more commonly classified as subtype CMTDIB | |
CMT2N | Online Mendelian Inheritance in Man (OMIM) 613287 | AARS | 16q22.1 | Autosomal dominant | ||
CMT2O | Online Mendelian Inheritance in Man (OMIM) 614228 | DYNC1H1 | 14q32.31 | Autosomal dominant | Allelic with spinal muscular atrophy with lower extremity predominance 1 | |
CMT2P | Online Mendelian Inheritance in Man (OMIM) 614436 | LRSAM1 | 9q33.3 | Autosomal dominant Autosomal recessive |
Juvenile or adult onset, slowly progressive | |
CMT2Q | Online Mendelian Inheritance in Man (OMIM) 615025 | DHTKD1 | 10p14 | Autosomal dominant | ||
CMT2R | Online Mendelian Inheritance in Man (OMIM) 615490 | TRIM2 | 4q31.3 | Autosomal recessive | ||
CMT2S | Online Mendelian Inheritance in Man (OMIM) 616155 | IGHMBP2 | 11q13.3 | Autosomal recessive | ||
CMT2T | Online Mendelian Inheritance in Man (OMIM) 617017 | MME | 3q25 | Autosomal recessive | ||
CMT2U | Online Mendelian Inheritance in Man (OMIM) 616280 | MARS | 12q13.3 | Autosomal dominant | ||
CMT2V | Online Mendelian Inheritance in Man (OMIM) 616491 | NAGLU | 17q21.2 | Autosomal dominant | ||
CMT2W | Online Mendelian Inheritance in Man (OMIM) 616625 | HARS1 | 5q31.3 | Autosomal dominant | ||
CMT2X | Online Mendelian Inheritance in Man (OMIM) 616668 | SPG11 | 15q21.1 | Autosomal recessive | ||
CMT2Y | Online Mendelian Inheritance in Man (OMIM) 616687 | VCP | 9p13.3 | Autosomal dominant | ||
CMT2Z | Online Mendelian Inheritance in Man (OMIM) 616688 | MORC2 | 22q12.2 | Autosomal dominant | ||
CMT2CC | Online Mendelian Inheritance in Man (OMIM) 616924 | NEFH | 22q12.2 | Autosomal dominant | ||
CMT2DD | Online Mendelian Inheritance in Man (OMIM) 618036 | ATP1A1 | 1p13.1 | Autosomal dominant | ||
CMT2EE | Online Mendelian Inheritance in Man (OMIM) 618400 | MPV17 | 2p23.3 | Autosomal recessive | ||
CMT3 | CMT3 | Online Mendelian Inheritance in Man (OMIM) 145900 | MPZ EGR2 PMP22 PRX |
1q23.3 10q21.3 17p12 19q13.2 |
Autosomal dominant Autosomal recessive |
More commonly known as Dejerine–Sottas disease; subtype CMT4F sometimes included here |
CMT4 | CMT4A | Online Mendelian Inheritance in Man (OMIM) 214400 | GDAP1 | 8q21.11 | Autosomal recessive | Allelic with subtype CMTRIA |
CMT4B1 | Online Mendelian Inheritance in Man (OMIM) 601382 | MTMR2 | 11q21 | Autosomal recessive | ||
CMT4B2 | Online Mendelian Inheritance in Man (OMIM) 604563 | SBF2 | 11p15.4 | Autosomal recessive | ||
CMT4B3 | Online Mendelian Inheritance in Man (OMIM) 615284 | SBF1 | 22q13.33 | Autosomal recessive | ||
CMT4C | Online Mendelian Inheritance in Man (OMIM) 601596 | SH3TC2 | 5q32 | Autosomal recessive | May lead to respiratory compromise | |
CMT4D | Online Mendelian Inheritance in Man (OMIM) 601455 | NDRG1 | 8q24.3 | Autosomal recessive | Characterised by demyelination and loss of hearing | |
CMT4E | Online Mendelian Inheritance in Man (OMIM) 605253 | MPZ EGR2 |
1q23.3 10q21.3 |
Autosomal recessive | Also known as congenital hypomyelinating neuropathy; phenotype largely overlapping with subtype CMT4F | |
CMT4F | Online Mendelian Inheritance in Man (OMIM) 145900 | PRX | 19q13.2 | Autosomal recessive | Phenotype largely overlapping with subtype CMT4E; may be the same as CMT3 | |
CMT4G | Online Mendelian Inheritance in Man (OMIM) 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 | Online Mendelian Inheritance in Man (OMIM) 609311 | FGD4 | 12p11.21 | Autosomal recessive | ||
CMT4J | Online Mendelian Inheritance in Man (OMIM) 611228 | FIG4 | 6q21 | Autosomal recessive | Allelic to amyotrophic lateral sclerosis type 11 | |
CMT5 | CMT5 | Online Mendelian Inheritance in Man (OMIM) 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 | CMT6 | Online Mendelian Inheritance in Man (OMIM) 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. |
CMTDI | CMTDIA | Online Mendelian Inheritance in Man (OMIM) 606483 | ? | 10q24.1–q25.1 | Autosomal dominant | |
CMTDIB | Online Mendelian Inheritance in Man (OMIM) 606482 | DNM2 | 19p13.2 | Autosomal dominant | Also classified as subtype CMT2M | |
CMTDIC | Online Mendelian Inheritance in Man (OMIM) 608323 | YARS | 1p35.1 | Autosomal dominant | ||
CMTDID | Online Mendelian Inheritance in Man (OMIM) 607791 | MPZ | 1q23.3 | Autosomal dominant | ||
CMTDIE | Online Mendelian Inheritance in Man (OMIM) 614455 | INF2 | 14q32.33 | Autosomal dominant | ||
CMTDIF | Online Mendelian Inheritance in Man (OMIM) 615185 | GNB4 | 3q26.33 | Autosomal dominant | ||
CMTRI | CMTRIA | Online Mendelian Inheritance in Man (OMIM) 608340 | GDAP1 | 8q21.11 | Autosomal recessive | Allelic with subtype CMT4A |
CMTRIB | Online Mendelian Inheritance in Man (OMIM) 613641 | KARS | 16q23.1 | Autosomal recessive | ||
CMTX2 | Online Mendelian Inheritance in Man (OMIM) 302801 | CMTX2 | Xq22.2 | X-linked recessive | ||
CMTX3 | Online Mendelian Inheritance in Man (OMIM) 302802 | CMTX3 | Xq26 | X-linked recessive | ||
CMTX4 | Online Mendelian Inheritance in Man (OMIM) 310490 | NAMSD | Xq24–q26.1 | X-linked recessive | Also known as Cowchock syndrome | |
CMTX5 | Online Mendelian Inheritance in Man (OMIM) 311070 | PRPS1 | Xq22.3 | X-linked recessive | Also known as Rosenberg–Chutorian syndrome; signs include optic atrophy, polyneuropathy and deafness | |
CMTX6 | Online Mendelian Inheritance in Man (OMIM) 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
- ↑ "Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy". The New England Journal of Medicine 362 (13): 1181–1191. April 2010. doi:10.1056/NEJMoa0908094. PMID 20220177.
- ↑ "The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes". Genome Research 11 (6): 1018–1033. June 2001. doi:10.1101/gr.180401. PMID 11381029.
![]() | Original source: https://en.wikipedia.org/wiki/Charcot–Marie–Tooth disease classifications.
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