Table 1.
Electrophysiological and histological evidence for secondary axon degeneration in demyelinating neuropathy patients and rodent models. Nerve conduction studies with evoked potentials were included as electrophysiological evidence; reduced compound muscle action potential (CMAP) amplitudes (↓CMAP), reduced sensory nerve action potential (SNAP) amplitudes (↓SNAP), reduced CMAP & SNAP Amplitudes (↓CMAP & ↓SNAP), reduced compound action potentials (↓CAP) and not specified (NS). Peripheral nerve biopsies demonstrating features of axon degeneration were included as histological evidence; axonal atrophy (AA), active axon degeneration (AD), axonal loss (AL), sxonal swellings (AS), axon sprouts/clusters of regenerating axons (ASC), bands of Büngner (BB) and myelin ovoids (MO). Reports inaccessible due to language barriers were excluded. Additional abbreviations: distal acquired demyelinating symmetric neuropathy (DADS), deletion (del), duplication (dup), experimental autoimmune neuritis (EAN), GM1 ganglioside (GM1), heterozygous (het), insertion (ins), knockout (KO), knockin (KI), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), not applicable (N/A), no reports (NR), super enhancer (SE), transgenic (Tg).
| Disease | Subtype | Sample | Electrophysiological Evidence for Secondary Axon Degeneration |
Histological Evidence for Secondary Axon Degeneration |
Mechanisms Involved |
|---|---|---|---|---|---|
| CMT1A (17p11.2-p12 Duplication [PMP22 Duplication]) | N/A | Patients |
↓CMAP [4, 39, 50, 61, 148, 173, 240, 270, 288, 297, 311, 323, 416, 419, 433, 451, 581, 585, 596, 623] ↓SNAP [563] ↓CMAP & ↓SNAP [27, 48, 49, 59, 94, 129, 137, 176, 195, 214, 223, 224, 228, 231, 293, 368, 370, 378, 424, 465, 509, 521, 593, 602, 634] |
AA [562] AD [421] AL [214, 378] ASC [85, 214, 501, 563, 623] |
Trophic support [494, 597], vulnerable to toxic insults [9, 102, 191, 241] |
| Rodents |
↓CMAP:
PMP22 Tg Mice (C61 [279, 284], TgN248 [364]), PMP22 Tg Rats [159, 192] ↓CMAP & ↓SNAP: PMP22 Tg Mice (C3-PMP [592], C22 [592]), PMP22 Tg Rats [514] |
AA:
PMP22 Tg Mice (C3-PMP [592], C22 [480, 592]), PMP22 Tg Rats [192] AD: PMP22 Tg Rats [514] AL: My41 PMP22 Tg Mice [480], PMP22 Tg Rats [159] ASC: C61 PMP22 Tg Mice [279] BB: PMP22 Tg Mice (C22 [480], My41 [480]) |
Nodal architecture [284], cytoskeletal organization [157, 192, 423, 489, 492, 500], cargo transport [489, 492, 592], trophic support [422, 494, 597] | ||
| HNPP (17p11.2-p12 Deletion [PMP22 Deletion]) | N/A | Patients |
↓CMAP [55, 80, 109, 177, 217, 240, 294, 429, 591, 618] ↓SNAP [19, 66, 110, 113, 185, 236, 299, 309, 319, 321, 342, 344, 351, 397, 404, 412, 439, 443, 460, 467, 567, 575, 615, 632] ↓CMAP & ↓SNAP [16, 17, 20, 23, 40, 53, 56, 88, 111, 112, 119, 152-154, 160, 186, 189, 193, 201, 210, 216, 219, 223, 226, 260, 268, 269, 285, 327, 367, 431, 435, 448, 455, 519, 533, 573] NS [36, 438, 515, 603] |
AA [226, 562] AD [226, 285, 351, 533, 603] AL [299, 351] ASC [216, 351, 515, 573, 603] MO [603] |
Cytoskeletal organization [124], vulnerable to toxic insults [253] |
| Rodents | ↓CMAP: PMP22 Het KO Mice [7, 229, 651] | AL: PMP22 SE Het del Mice [442] | NR | ||
| CMT1B (MPZ Point Mutationa) | Infantile-onset | Patients |
↓CMAP: p.I30S [393], p.I30T [161], p.T65N [77], p.H81Qb [99], p.H81Rb [151], p.R98C [30, 32], P.G103W [77], p.S121F [516], p.G123D [72], p.T124K [282], p.C127Y [144], p.D128Nb [151], p.K130R [635], p.N131K [280], p.P132L [135], p.D134E [30], p.I135T [135], p.G137R [532], p.L175SfsX74 [612], p.L184AfsX50 [553], p.L184AfsX51 [537], p.A209EfsX24 [30], p.Q215X [366] ↓CMAP & ↓SNAP: p.P105L [346], p.N131S [232], p.G137_K149del [559], p.K207X [652] NS: p.D90Eb [358] |
AL: p.R98C [32], p.G167R [560] AD: p.D90Eb [60, 358], p.R98C [612], p.K130R [635] ASC: p.H81Qb [99], p.R98C [317], p.G167R [560] MO: p.D90Eb [60] |
Nodal architecture [32], cytoskeletal organization [387] |
| Rodents | ↓CMAP: p.R98C KI Mice [505] | NR | NR | ||
| Adolescent-onset | Patients |
↓CMAP: p.V58D [317], p.T65A [281], p.R98Hb [307, 540], p.Q100X [393], p.V102CfsX11b [107], p.D109N [307], p.I135M [336], p.Q187PfsX63 [336] ↓SNAP: p.V102CfsX11b [107] ↓CMAP & ↓SNAP: p.K48Qb [77], p.E97AfsX5b [77], p.K214M [35], p.K236del [541], c.645 + 1G>Tb,d [77, 275] NS: p.G123Sb [318] |
AL: p.V58D [317], p.R98Hb [307] ASC: p.R98Hb [307], p.D109N [307], p.G123Sb [318], p.S233RfsX18 [317] |
NR | |
| Rodents | ↓CMAP: p.S63del Tg Mice [619] | AD: p.S63del Tg Mice [619] | NR | ||
| Adult-onset | Patients |
↓CMAP: p.H39P [325, 539], p.S51F [640], p.S54VfsX5d [92], p.I62M [26], p.E71X [306], p.S78Lb [150, 151, 262, 381, 640], p.H81L [339], p.F95L [427], p.I99T [131], p.T124A [365], p.T124Mc [301, 302, 314, 339], p.L144RfsX18[534], p.Y145LfsX4 [365], p.Y145Sc [313, 543], p.G163R [140] ↓SNAP: p.S20F [156], p.D104TfsX14 [116] ↓CMAP & ↓SNAP: p.D35N [72], p.R36G [114], p.R36W [81], p.H39P [266], p.V46M [77], p.S55I [275], p.E56K [283], p.D60H [27], p.P70S [310], p.D75V [394], p.Y82H [58], p.D104TfsX14c [353, 445], p.P105T [251], p.R106C [375], p.D109E [503], p.N116S [275], p.D121N [136], p.T124M [74, 91, 118, 174, 207, 394, 513, 547, 565, 570], p.V136Gc [475], p.T143R [77], p.Y145X [363], p.V146G [77], p.V150 S195del [486], p.P151AfsX3 [456], p.D224Yc [147, 508], p.H225QfsX10b [215], p.R227G [523] |
AA: p.D61G [513], p.Y119C [513], p.T124M [394, 513] AL: p.S20F [156], p.D35Y [376], p.S51F [640], p.D61G [513], p.I99T [131], p.Y119C [513], p.T124M [32, 91, 118, 207, 301, 513], p.D224Y [508], AD: p.D35Y [376], p.D61G [513], p.P70S [310], p.Y119C [513], p.T124M [91, 301, 302, 394, 513], p.D224Y [508] ASC: p.R36G [114], p.H39P [266, 325], p.S44F [151], p.D61G [513], p.P70S [310], p.E71X [306], p.Y82H [58], p.I99T [131], p.D104TfsX14c [445], p.Y119C [513], p.T124M [32, 74, 91, 118, 151, 207, 301, 394, 513, 547, 638], p.D224Y [508], p.R227G [523] BB: p.D61G [513], p.Y119C [513], p.T124M [513], p.R227G [523] MO: p.R36G [114], p.T124M [301], p.R227G [523] |
Nodal architecture [325], cytoskeletal organization [207] | |
| Rodents | NR | NR | NR | ||
| CMT1C (LITAF Point Mutation) | N/A | Patients |
↓CMAP: p.T49Mf [495], p.G112Sg [244] ↓SNAP: p.G112S [265] ↓CMAP & ↓SNAP: p.I92V [506], P.G112S [495], p.P135R [103], p.V144M [182] |
AL: p.T49Mf [495], p.P135R [103] ASC: p.P135R [103] |
NR |
| Rodents | ↓CMAP: p.W116G Tg Mice [316] | AD: p. W116G Tg Mice [316] | Nodal architecture [316], cargo transport [316] | ||
| CMT1D (EGR2 Point Mutation) | N/A | Patients |
↓CMAP: p. I268Nc [613], P.R359W [100, 564], p.R381C [637], p.R381H [447], p.S382R + p.D383Y [613], p.D411G [194] ↓SNAP: p.R353G [415], p.R359W [178], p.T387N [522] ↓CMAP & ↓SNAP: p.R359Q [391], p.R381C [75], p.R409Q [517], p.R409W [322], p.E412G [487, 568] NS: p.R381C [611] |
AL: p.R359W [100, 564], pE412G [568] AD: pE412G [568] ASC: p.D355V [411], pE412G [568] |
Cytoskeletal organization [564, 613], vulnerable to toxic insults [415] |
| Rodents | N/R | N/R | Nodal architecture [34] | ||
| CMT1E (PMP22 Point Mutation) | N/A | Patients |
↓CMAP: p.S7YfsX30 [326], p.L18R [362], p.S22F [484], p.W28X [87], p.W39C [557], p.S72L [371, 531], p.L78P [461], p.Q86X [335], p.T99_G100del [290], p.Q103X [461], p.I104FfsX7 [335], p.G107VfsX4 [215], p.C109R [149], p.V110_I116dup [290], p.S112R [252], p.A115_T118del [499], p.T118Mc,h [528], p.Y136_A139del [598], p.G150D [237], p.X161WextX10c [644], c.178 + 2T>C [169], c.179 - 1G>A [261], c.319 + 1G>A [335], c.417 + 2T>G [609], 17p11.2-p12 del/p.W61X [248], 17p11.2-p12 del/p.T118Mh [528], 17p11.2-p12 del/Exon 2+3 deli [14], 17p11.2-p12 del/Exon 5 deli [1, 113] ↓SNAP: p.S7YfsX30 [420], p.C42R [335], p.R95QfsX128 [321], p.G100EfsX11 [403], p.I116TfsX5[558], p.L145PfsX78 [646], Exon 4+5 deli [552, 587] ↓CMAP & ↓SNAP: p.L4RfsX3 [405], p.S22F [277], p.T23R [356], p.S76TfsX35 [350], p.R95QfsX128 [120], p.Y97TfsX14 [643], p.C109X [3], p.T118Mh [484], p.S131C [484], p.L145RfsX10 [55], p.R159C [183], c.78 + 5G>Ac [622], c.79 - 2A>G [290], c.179 + 1G>C [43], Exon 5 deli [1, 86], 17p11.2-p12 del/p.T118Mh [243] |
AA: p.V30M [491], c.179 - 1G>C [389] AL: p.L18R [362], p.T23R [246], p.S149R [430], 17p11.2-p12 del/Exon 2+3 deli [14] AD: p.S72L [65], p.R159C [183] AS: p.R159C [183] ASC: p.S76TfsX35 [350], p.R95QfsX128 [120], p.C109X [3], p.R159C [183], c.179 - 1G>C [389], 17p11.2-p12 del/p.R157G [425] MO: p.C109X [3] |
Cytoskeletal organization [3, 491] |
| Rodents | ↓CMAP: TremblerJ (p.L16P) Mice [128, 384, 385, 493] |
AA: TremblerJ (p.L16P) Mice [480] AD: Trembler (p.G150D) Mice [220, 361] AL: TremblerJ (p.L16P) Mice [479], Trembler-m1H (p.H12R) Mice [238], Trembler-m2H (p.Y153X) Mice [238], Trembler-m3H (p.S72T) [238] BB: TremblerJ (p.L16P) Mice [480] |
Nodal architecture [128, 198, 418, 477, 482, 610], cytoskeletal organization [121-123, 220, 263, 273, 347, 463, 491, 493, 544], cargo transport [121-123, 463, 482], trophic support [165, 494] | ||
| CMT1F (NEFL Point Mutation) | N/A | Patients |
↓CMAP: p.P8L [247], p.P8Q [247], p.P8R [117, 225, 247, 337, 392], p.P22S [142, 181, 337], p.E90K [247], p.L93P [392], p.N98S [54, 225, 247, 354, 630, 639], p.E163Xc [167], p.L268P [143], p.L311P [225], p.Q333P [388], p.Y389C [213], p.E396K [141, 337, 459] ↓CMAP & ↓SNAP: p.P22R [524], p.P22S [57, 359], p.P22T [639], p.E210Xc [642], p.C322_N326del [143], p.E396K [52, 143], p.E397K [653], p.R421X [10] |
AA: p.P22S [142], p.E396K [141] AD: p.C322_N326del [143], p.E396K [141], p.E397K [653] AL: p.P8R [225], p.N98S [225, 354], p.N272K [134] AS: p.P22S [142, 359], p.N98S [354], p.L268P [143], p.N272K [134], p.C322_N326del [143], p.E397K [653], p.P440L [45] ASC: p.P8R [225], p.P22S , p.E90K [2, 247], p.N98S [2], p.E140Xc [2], p.E163Xc [167], p.E210Xc [642], p.L268P [143], p.N272K [134], p.C322_N326del [143], p.Y389C [213], p.E396K [2, 141, 143], p.E397K [653], p.P440L [45] BB: p.E397K [653] MO: p.E90K [247], p.P440L [45] |
Cytoskeletal organization [45, 134, 142, 143, 167, 359, 642, 653], cargo transport [141, 143, 213, 359, 653] |
| Rodents | ↓CAP: p.N98S KI Mice [308] |
AD: p.N98S KI Mice [308] AL: p.N98S KI Mice [308], p.E396K Tg Mice [599] ASC: p.N98S KI Mice [308] |
Cytoskeletal organization [6, 127, 308, 504, 648], cargo transport [127, 308, 504, 648] | ||
| CMT1X (GJB1 Point Mutation or Deletionj) | N/A | Patients |
↓CMAP: p.M1I [572], p.T4K [393], p.L6S [572], p.L9F [78], p.S11C [93], p.N14K [93], p.R15L [349], p.R15Q [82, 203], p.R15W [259], p.H16L [262], p.I20F [572], p.G21D [349], p.W24C [315], p.S26L [203, 550, 572], p.S26W [138, 640], p.R32G [262], p.V35L [334], p.A39S [349], p.S49Y [572], p.I52TfsX31 [393], p.T55I [203, 259], p.T55R [315], p.V63I [561], p.C64F [640], p.C64Y [257, 550], p.Y65C [349], p.Y65H [510], p.S72F [332], p.R75P [395], p.V91M [63, 572], p.M93K [393], p.V95M [399], p.I101RfsX8 [572], p.E102X [203, 554, 640], p.E109X [315], p.V120E [259], P.V125D [315], p.I127M [332], p.V139M [203], p.R142Q [93], p.R142W [349], p.L144del [572], p.F153L [572], p.Y160H [262], p.R164K [437], p.R164Q [259], p.R164W [349, 525, 640], p.V170D [262], p.C173Y [572], p.V177del [650], p.C179G [402], p.R183C [203, 572], p.R183H [349, 572], p.E186K [349, 561], p.T191fsi [315], p.I202D [341], p.E208K [203], p.Y211X [203], p.L212F [78], p.R215P [572], P.R215W [550, 640], p.R220X [572], c.-5413_-49del [298], c.-529 T>C [571], c.-146-90_-146-89insT [566], c.-17 + 1G>T [566], c.*15 C>T [95], GJB1 Deletioni [11, 414] ↓SNAP: p.N2S [340], p.H16L [606], p.E102del [616], p.F153S [315], p.S198A [393] ↓CMAP & ↓SNAP: p.MIR [78], p.N2K [96], p.W3G [352], p.W3X [340], p.T8I [130], p.N14S [542], p.R15Q [550], p.R15W [200, 511], p.I20T [349], p.R22Q [511, 561], p.R32K [33], p.I33N [382, 616], p.V35M [332], p.V37GfsX47 [338], p.V38A [258], p.A40T [360], p.E41D [410], p.N54H [536], p.N54S [616], p.C60Y [22], p.V63F [78], p.I71S [626], p.R75CfsX8 [72], p.L81P [340], p.P87L [300], p.L90P [340], p.A88D [349], p.M93R [616, 649], p.V95M [550], p.A96V [190], p.Q99_H100insQ [488], p.H100Q [257], p.H100Y [197], p.L106P [340], p.R107MfsX10 [485], P.I127S [605], p.I127F [349], p.I127N [349], p.I127T [230], p.W133GfsX63 [496, 616], p.Y135LfsX12 [349], p.V137A [551], p.V140E [278], p.R142E [334], p.R142Q [548], p.L143P [278], p.L144W [190], p.F145C [340], p.A147PfsX49 [386], p.F149L [627], p.L156AfsX37 [579], p.R164Q [550, 616], p.R164W [550], p.L165Q [190], p.V170F [257], p.P172L [550], p.C179Y [72], p.S182T [332], p.R183C [349], p.T188I [334], p.T191_F193dup [590], p.F193S [190], p.A197V [349], p.L204F [550], p.N205S [31], p.Y211X [205], p.R224L [190], p.S277GfsX128 [393], p.R238C [373], p.K260E [257], p.I262TfsX13 [67], c.-529 T>C [41], c.-459 C>T [329, 571], c.-215 G>A [624], c.-170 T>G [357], c.-103 C>T [566], c.-17 G>A [409, 566], c.*15 C>T [566], GJB1 Deletioni [83, 561] NS: p.Y211H [63], p.S62R [330], p.S128L [380], p.R142Q [212], p.L156R [621], p.V177A [18] |
AA: p.N2K [96], p.R15W [511], p.R22Q [511], p.E102G [490], p.I127S [605] AL: p.R15W [617], p.D46G [449], p.L108P [65], p.Y211H [63], p.F235C [333] AD: p.H16L [606], p.R22Q [561], p.S26L [203], p.V63I [561], p.P87L [203, 300], p.H94R [600], p.V95M [600], p.I127S [605], p.L156AfsX37 [579], p.R183C [203, 600], p.E186K [561], p.E208K [203], p.Y211X [203, 205], p.R215W [600], p.R219C [600], c.-17 G>A [409], GJB1 Deletioni [203, 414, 561] ASC: p.N2K [96], p.R15Q [82, 203], p.R15W [200, 511, 512], p.H16L [606], p.R22Q [511, 512, 561], p.R22X [62], p.A39V [512], p.F69L [638], p.P87L [300], p.E102G [490], p.I127Fk [470], p.I127S [605], 561], p.S128X [638], p.V140E [278], p.L156AfsX37 [579], p.P158A [62], p.D178Gk [470], p.E208K [203, 204], p.Y211X [205], p.P227SfsX16 [512], c.-5413_-49del [298], c.-459 C>T [329], c.-215 G>A [624], c.-19 C>G [45], c.-17 G>A [409, 566], GJB1 Deletioni [11, 203, 414] MO: c.-17 G>A [409] NS: p.V91M [390], p.T191fsi [315] |
Cytoskeletal organization [203, 204, 490], cargo transport [490], vulnerable to toxic insults [464] |
| Rodents | ↓CMAP: Cx32 KO Mice [21] |
AL: Cx32 KO Mice [507] ASC: Cx32 KO Mice [21, 507] |
Cytoskeletal organization [490, 507, 589], cargo transport [490, 589] | ||
| AIDP1 (Acute Immune Response Targeting PNS) | N/A | Patients |
↓CMAP: [47, 227, 239, 254, 264, 400, 444, 535, 549] ↓SNAP: [76, 304, 578] ↓CMAP & ↓SNAP: [13, 15, 37, 51, 89, 125, 175, 196, 436, 518, 582, 608, 629] NS: [469] |
AD: [47, 51, 84, 202, 295, 348, 406, 469] AL: [51, 84, 406] ASC: [47, 51] BB: [51, 406] MO: [254, 406, 469] |
Cytoskeletal organization [84] |
| Rodents |
↓CMAP: Severe EAN Mice [625] ↓SNAP: AIDP Patient IG Mice [115] ↓CAP: Guinea Pig Myelin EAN Rats [343] |
AL: Severe EAN Mice [625] AD: Guinea Pig Myelin EAN Rats [343], PMP2 EAN Rats [245, 343] |
Nodal architecture [343] | ||
| CIDP (Chronic Immune Response Targeting PNS) | Mixed/Not Classified | Patients |
↓CMAP: Unknown Ig [188, 233, 444, 473] ↓CMAP & ↓SNAP: CNTN1 IgG4 [289, 471], NF-155 IgG4 [289, 428], Unknown Ig [38, 199, 211, 289, 428, 432, 586] NS: GM1 IgM [255], IgGγ [601], IgGκ [601], IgMγ [601], IgMκ [601], IgGκ + IgMκ [601] |
AD: CASPR IgG4 [132], IgGγ [601], IgGκ [601], IgMγ [601], IgMκ [601], IgGκ + IgMκ [601], Unknown Ig [28, 38, 139, 188, 209, 271, 295, 355, 413, 432, 457, 468, 497] AL: CASPR IgG4 [132], CNTN1 IgG4 [289], Unknown Ig [71, 164, 188, 296, 355] ASC: Unknown Ig [71, 101, 271, 296, 355, 457, 468, 586, 604] MO: Unknown Ig [604] |
Nodal architecture [101, 132], cytoskeletal organization [164, 413, 468, 478, 604], cargo transport [604] |
| Typical | Patients |
↓CMAP: Unknown Ig [155] ↓CMAP & ↓SNAP: Unknown Ig [234] |
AD: CNTN1 IgG4 [133, 286], NF-155 IgG4 [286], Unknown Ig [234, 286] AL: CNTN1 IgG4 [133, 286], NF-155 IgG4 [286], Unknown Ig [286] ASC: Unknown Ig [234, 584] MO: CNTN1 IgG4 [286], NF-155 IgG4 [286] |
NR | |
| DADS | Patients |
↓CMAP: Unknown Ig [155, 434] ↓CMAP & ↓SNAP: Unknown Ig [234] |
AD: NF-155 IgG4 [286], Unknown Ig [234, 286, 434] AL: NF-155 IgG4 [286], Unknown Ig [286] ASC: Unknown Ig [234, 584] MO: NF-155 IgG4 [286], Unknown Ig [434] |
NR | |
| MADSAM | Patients | ↓CMAP & ↓SNAP: Unknown Ig [234] |
AD: Unknown Ig [234, 286] AL: Unknown Ig [286] ASC: Unknown Ig [234] |
NR | |
| Pure Motor | Patients | ↓CMAP: IgE [272] | NR | NR | |
| Pure Sensory | Patients | ↓CMAP & ↓SNAP: Unknown Ig [234] |
AD: Unknown Ig [234, 286] ASC: Unknown Ig [584] |
NR | |
| N/A | Rodents |
↓ CMAP: B7-2–Deficient Nod Mice [498, 577], Bovine Peripheral Nerve Myelin Immunized Rats [250], PMP2 EAN Rats [218] ↓ CAP: CNTN1 IgG4 Treated Rats [369] |
AD: B7-2–Deficient Nod Mice [577], Bovine Peripheral Nerve Myelin Immunized Rats [250], PMP2 EAN Rats [483] AL: B7-2–Deficient Nod Mice [577] |
Nodal architecture [369] |
a
MPZ amino acid number corresponds to the full-length protein containing the leader peptide.
b
The same MPZ mutation occasionally causes a spectrum of disease onset. These mutations were included in the most common or earliest disease onset group in the table: infantile- and adolescent-onset (p.H81Q, p.H81R, p.D90E), adolescent- and adult-onset (p.K48Q, p.E97AfsX5, p.V102CfsX11, p.G123S, p.H225QfsX10, c.645 + 1G>T) and infantile-, adolescent- and adult-onset (p.S78L, p.R98H, p.D128N).
c
Mutations are generally heterozygous but homozygous mutations has also been identified and they frequently present with more severe CMT than their heterozygous relatives.
d
Some patients were also diagnosed with well-controlled diabetes.
e
Insufficient details were provided to accurately determine disease onset age.
f
LITAF p.T49M pathogenicity is controversial [41].
g
A PRX variant (p.R187C) of unknown significance in was also identified in this patient.
i
Proper nomenclature could not be established based on reported mutation.
j
Both male and female CMT1X patients were included.
k
The abstracts of some reports that were inaccessible due to language barriers contained sufficient information to be included. However, it is unclear if the full text provides additional evidence.
l
Reports demonstrating a lack of denervation by electromyography without supporting histological evidence for secondary axon degeneration were excluded.