charcot–marie–tooth disease classifications 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 cmt1cmt1a 118220pmp2217p11.2autosomal dominantthe 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 118200mpz1q23.3autosomal dominantresponsible for 5–10% of type 1 patients. average ncv: < 15 m/s cmt1c 601098litaf16p13.13autosomal dominantusually shows up in infancy. average ncv: 26–42 m/s. symptoms are identical to cmt1a. cmt1d 607678egr210q21.3autosomal dominantaverage ncv: 15–20 m/s cmt1e 118300pmp2217p11.2autosomal dominantcharacterised by demyelination and loss of hearing; allelic with subtype cmt1a cmt1f 607734nefl8p21.2autosomal dominant cmt1g 618279pmp28q21.13autosomal dominant cmt2cmt2a1 118210kif1b1p36.22autosomal dominant cmt2a2a 609260mfn21p36.22autosomal dominant cmt2a2b 617087mfn21p36.22autosomal recessive cmt2b 600882rab7arab7b3q21.3autosomal dominant cmt2b1 605588lmna1q22autosomal recessivea laminopathy cmt2b2 605589med2519q13.33autosomal dominant cmt2c 606071trpv412q24.11autosomal dominantmay cause vocal cord, diaphragm, and distal weakness cmt2d 601472gars7p14.3autosomal dominantsymptoms are more severe in the upper extremities (hands), which is atypical for cmt cmt2e 607684nefl8p21.2autosomal dominant cmt2f 606595hspb17q11.23autosomal dominant cmt2h 607731gdap18q21.11autosomal dominantallelic with subtype cmt2k cmt2i 607677mpz1q23.3autosomal dominantallelic with subtype cmt2j and forms of cmt3 cmt2j 607736mpz1q23.3autosomal dominantallelic with subtype cmt2i and forms of cmt3 cmt2k 607831gdap18q21.11autosomal dominantallelic with subtype cmt2h cmt2l 608673hspb812q24.23autosomal dominantallelic with autosomal dominant distal spinal muscular atrophy cmt2m 606482dnm219p13.2autosomal dominantfull name: cmt2m, included; more commonly classified as subtype cmtdib cmt2n 613287aars16q22.1autosomal dominant cmt2o 614228dync1h114q32.31autosomal dominantallelic with spinal muscular atrophy with lower extremity predominance 1 cmt2p 614436lrsam19q33.3autosomal dominantautosomal recessivejuvenile or adult onset, slowly progressive cmt2q 615025dhtkd110p14autosomal dominant cmt2r 615490trim24q31.3autosomal recessive cmt2s 616155ighmbp211q13.3autosomal recessive cmt2t 617017mme3q25autosomal recessive cmt2u 616280mars12q13.3autosomal dominant cmt2v 616491naglu17q21.2autosomal dominant cmt2w 616625hars15q31.3autosomal dominant cmt2x 616668spg1115q21.1autosomal recessive cmt2y 616687vcp9p13.3autosomal dominant cmt2z 616688morc222q12.2autosomal dominant cmt2cc 616924nefh22q12.2autosomal dominant cmt2dd 618036atp1a11p13.1autosomal dominant cmt2ee 618400mpv172p23.3autosomal recessive cmt3cmt3 145900mpzegr2pmp22prx1q23.310q21.317p1219q13.2autosomal dominantautosomal recessivemore commonly known as dejerine–sottas disease; subtype cmt4f sometimes included here cmt4cmt4a 214400gdap18q21.11autosomal recessiveallelic with subtype cmtria cmt4b1 601382mtmr211q21autosomal recessive cmt4b2 604563sbf211p15.4autosomal recessive cmt4b3 615284sbf122q13.33autosomal recessive cmt4c 601596sh3tc25q32autosomal recessivemay lead to respiratory compromise cmt4d 601455ndrg18q24.3autosomal recessivecharacterised by demyelination and loss of hearing cmt4e 605253mpzegr21q23.310q21.3autosomal recessivealso known as congenital hypomyelinating neuropathy; phenotype largely overlapping with subtype cmt4f cmt4f 145900prx19q13.2autosomal recessivephenotype largely overlapping with subtype cmt4e; may be the same as cmt3 cmt4g 605285hk110q22.1autosomal recessivealso known as russe-type hereditary motor and sensory neuropathy (hmsnr); second most common cause of cmt in the spanish roma population cmt4h 609311fgd412p11.21autosomal recessive cmt4j 611228fig46q21autosomal recessiveallelic to amyotrophic lateral sclerosis type 11 cmt5cmt5 600361 ?4q34.3–q35.2autosomal dominantalso known as cmt with pyramidal features; onset in 2nd decade of life with distal muscle wasting, particularly in legs cmt6cmt6 601152mfn21p36.22autosomal dominantcharacterised by optic atrophy, hence known also as cmt with optic atrophy. also known as hereditary motor and sensory neuropathy type vi. cmtdicmtdia 606483 ?10q24.1–q25.1autosomal dominant cmtdib 606482dnm219p13.2autosomal dominantalso classified as subtype cmt2m cmtdic 608323yars1p35.1autosomal dominant cmtdid 607791mpz1q23.3autosomal dominant cmtdie 614455inf214q32.33autosomal dominant cmtdif 615185gnb43q26.33autosomal dominant cmtricmtria 608340gdap18q21.11autosomal recessiveallelic with subtype cmt4a cmtrib 613641kars16q23.1autosomal recessive cmtxcmtx1 302800gjb1xq13.1x-linked dominantresponsible 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. cmtx2 302801cmtx2xq22.2x-linked recessive cmtx3 302802cmtx3xq26x-linked recessive cmtx4 310490namsdxq24–q26.1x-linked recessivealso known as cowchock syndrome cmtx5 311070prps1xq22.3x-linked recessivealso known as rosenberg–chutorian syndrome; signs include optic atrophy, polyneuropathy and deafness cmtx6 300905pdk3xp22.11x-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.