Charcot–Marie–Tooth disease classifications

Classifications of Charcot–Marie–Tooth disease refers to the types and subtypes of Charcot–Marie–Tooth disease, 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.
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		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, it is called Roussy–Lévy syndrome.
CMT1	CMT1B		MPZ	1q23.3	Autosomal dominant	Responsible for 5–10% of Type 1 patients. Average NCV: < 15 m/s
CMT1	CMT1C		LITAF	16p13.13	Autosomal dominant	Usually shows up in infancy. Average NCV: 26–42 m/s. Symptoms are identical to CMT1A.
CMT1	CMT1D		EGR2	10q21.3	Autosomal dominant	Average NCV: 15–20 m/s
CMT1	CMT1E		PMP22	17p11.2	Autosomal dominant	Characterised by demyelination and loss of hearing; allelic with subtype CMT1A
CMT1	CMT1F		NEFL	8p21.2	Autosomal dominant
CMT1	CMT1G		PMP2	8q21.13	Autosomal dominant
CMT2	CMT2A1		KIF1B	1p36.22	Autosomal dominant
CMT2	CMT2A2A		MFN2	1p36.22	Autosomal dominant
CMT2	CMT2A2B		MFN2	1p36.22	Autosomal recessive
CMT2	CMT2B		RAB7A RAB7B	3q21.3	Autosomal dominant
CMT2	CMT2B1		LMNA	1q22	Autosomal recessive	A laminopathy
CMT2	CMT2B2		MED25	19q13.33	Autosomal dominant
CMT2	CMT2C		TRPV4	12q24.11	Autosomal dominant	May cause vocal cord, diaphragm, and distal weakness
CMT2	CMT2D		GARS	7p14.3	Autosomal dominant	Symptoms are more severe in the upper extremities, which is atypical for CMT
CMT2	CMT2E		NEFL	8p21.2	Autosomal dominant
CMT2	CMT2F		HSPB1	7q11.23	Autosomal dominant
CMT2	CMT2H		GDAP1	8q21.11	Autosomal dominant	Allelic with subtype CMT2K
CMT2	CMT2I		MPZ	1q23.3	Autosomal dominant	Allelic with subtype CMT2J and forms of CMT3
CMT2	CMT2J		MPZ	1q23.3	Autosomal dominant	Allelic with subtype CMT2I and forms of CMT3
CMT2	CMT2K		GDAP1	8q21.11	Autosomal dominant	Allelic with subtype CMT2H
CMT2	CMT2L		HSPB8	12q24.23	Autosomal dominant	Allelic with distal spinal muscular atrophy">Anatomical terms of location">distal spinal muscular atrophy
CMT2	CMT2M		DNM2	19p13.2	Autosomal dominant	Full name: CMT2M, included; more commonly classified as subtype CMTDIB
CMT2	CMT2N		AARS	16q22.1	Autosomal dominant
CMT2	CMT2O		DYNC1H1	14q32.31	Autosomal dominant	Allelic with spinal muscular atrophy with lower extremity predominance 1
CMT2	CMT2P		LRSAM1	9q33.3	Autosomal dominant Autosomal recessive	Juvenile or adult onset, slowly progressive
CMT2	CMT2Q		DHTKD1	10p14	Autosomal dominant
CMT2	CMT2R		TRIM2	4q31.3	Autosomal recessive
CMT2	CMT2S		IGHMBP2	11q13.3	Autosomal recessive
CMT2	CMT2T		MME	3q25	Autosomal recessive
CMT2	CMT2U		MARS	12q13.3	Autosomal dominant
CMT2	CMT2V		NAGLU	17q21.2	Autosomal dominant
CMT2	CMT2W		HARS1	5q31.3	Autosomal dominant
CMT2	CMT2X		SPG11	15q21.1	Autosomal recessive
CMT2	CMT2Y		VCP	9p13.3	Autosomal dominant
CMT2	CMT2Z		MORC2	22q12.2	Autosomal dominant
CMT2	CMT2CC		NEFH	22q12.2	Autosomal dominant
CMT2	CMT2DD		ATP1A1	1p13.1	Autosomal dominant
CMT2	CMT2EE		MPV17	2p23.3	Autosomal recessive
CMT3	CMT3		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		GDAP1	8q21.11	Autosomal recessive	Allelic with subtype CMTRIA
CMT4	CMT4B1		MTMR2	11q21	Autosomal recessive
CMT4	CMT4B2		SBF2	11p15.4	Autosomal recessive
CMT4	CMT4B3		SBF1	22q13.33	Autosomal recessive
CMT4	CMT4C		SH3TC2	5q32	Autosomal recessive	May lead to respiratory compromise
CMT4	CMT4D		NDRG1	8q24.3	Autosomal recessive	Characterised by demyelination and loss of hearing
CMT4	CMT4E		MPZ EGR2	1q23.3 10q21.3	Autosomal recessive	Also known as congenital hypomyelinating neuropathy; phenotype largely overlapping with subtype CMT4F
CMT4	CMT4F		PRX	19q13.2	Autosomal recessive	Phenotype largely overlapping with subtype CMT4E; may be the same as CMT3
CMT4	CMT4G		HK1	10q22.1	Autosomal recessive	Also known as Russe-type hereditary motor and sensory neuropathy ; second most common cause of CMT in the Spanish Roma population
CMT4	CMT4H		FGD4	12p11.21	Autosomal recessive
CMT4	CMT4J		FIG4	6q21	Autosomal recessive	Allelic to amyotrophic lateral sclerosis type 11
CMT5	CMT5		?	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		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.
CMT6	CMT6B		SLC25A46	5q22.1	Autosomal recessive	Characterised by optic atrophy, hence known also as CMT with optic atrophy. Also known as hereditary motor and sensory neuropathy type VI.
CMT6	CMT6C		PDXK	21q22.3	Autosomal recessive	Characterised by optic atrophy, hence known also as CMT with optic atrophy. Also known as hereditary motor and sensory neuropathy type VI.
CMTDI	CMTDIA		?	10q24.1–q25.1	Autosomal dominant
CMTDI	CMTDIB		DNM2	19p13.2	Autosomal dominant	Also classified as subtype CMT2M
CMTDI	CMTDIC		YARS	1p35.1	Autosomal dominant
CMTDI	CMTDID		MPZ	1q23.3	Autosomal dominant
CMTDI	CMTDIE		INF2	14q32.33	Autosomal dominant
CMTDI	CMTDIF		GNB4	3q26.33	Autosomal dominant
CMTRI	CMTRIA		GDAP1	8q21.11	Autosomal recessive	Allelic with subtype CMT4A
CMTRI	CMTRIB		KARS	16q23.1	Autosomal recessive
CMTX	CMTX1		GJB1	Xq13.1	X-linked dominant	Responsible for approximately 90% of CMTX patients; some studies put this number significantly higher. Note that different mutations of GJB1 may produce markedly different forms of Charcot–Marie–Tooth disease.
CMTX	CMTX2		CMTX2	Xq22.2	X-linked recessive
CMTX	CMTX3		CMTX3	Xq26	X-linked recessive
CMTX	CMTX4		NAMSD	Xq24–q26.1	X-linked recessive	Also known as Cowchock syndrome
CMTX	CMTX5		PRPS1	Xq22.3	X-linked recessive	Also known as Rosenberg–Chutorian syndrome; signs include optic atrophy, polyneuropathy and deafness
CMTX	CMTX6		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.