Medicine:Charcot–Marie–Tooth disease classifications

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.

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	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.