Antibody & Biopsy
Patient Information


CMT & HMSN: Demyelinating
    CMT 1A: PMP-22; 17p12
    CMT 1B: P0 protein; 1q23
    CMT 1C: LITAF; 16p13
    CMT 1D: EGR2; 10q21
    CMT 1E (Deafness)
      PMP-22: 17p12
      P0 protein: 1q23
    CMT 1F: NEFL; 8p21
    CMT 1G: PMP2; 8q21
    CMT1: FBLN5; 14q32
      PMP-22 (Deletion or Point); 17p12
      KARS; 16q23
    HMSN 3 (Dejerine-Sottas)
        PMP-22; P0; 8q23; EGR2
    PNS & CNS hypomyelin: SOX10; 22q13
    Sensory PN + Hearing loss: GJB3; 1p34
    Hypomyelination: ARHGEF10; 8p23
    CMT-DIF: GNB4; 3q26
    HMSN: HARS; 5q31

  Recessive: Also AR-CMT1
    CMT 4A: GDAP1; 8q21
    CMT 4B1: MTMR2; 11q22
    CMT 4B2: SBF2; 11p15
    CMT 4B3: SBF1; 22q13
    CMT 4C: SH3TC2 (KIAA1985); 5q32
    CMT 4D (Lom): NDRG1; 8q24
    CMT 4E: EGR2; 10q21
    CMT 4F: Periaxin; 19q13
    HMSN-Russe (4G): HK1; 10q22
    CMT 4H: FGD4; 12q12
    CMT 4J: FIG4; 6q21
    CMT 4K: SURF1; 9q34
    HMSN 3 (Dejerine-Sottas)
        P0; PMP-22; EGR2; Periaxin
    HMSN + Juvenile glaucoma
    Cataracts (CCFDN): CTDP1; 18qter
    Cockayne's: 5
    Congenital hypomyelinating
        P0, PMP-22 & EGR-2
    Farber lipogranulomatosis: ASAH; 8p22
    CDG1a: PMM2; 16p13
    Krabbe: GALC; 14q31
    MLD: ARSA; 22q13
    PMP-22 point mutations
    Refsum's disease
        Childhood: PHYH; 10pter-p11.2
        Adolescent-Adult: PEX7; 6q22
        Infant: PEX1; 7q21
        PHARC: ABHD12; 20p11
        PBD8B: PEX16; 11p11
    HMSN +
      CNS: Heterogeneous
      Neurodegeneration: DNAJC3; 13q32

    CMTX1 (Males): GJB1 (CX32); Xq13
    CMTX3: Xq27
    Pyramidal signs
CMT & HMSN: Axonal
    CMT 2A2A: MFN2; 1p36
    ? CMT 2A1: KIF1B; 1p36
    CMT 2B: RAB7; 3q21
    CMT 2C: TRPV4; 12q24
    CMT 2D: GARS; 7p14
    CMT 2E: NEFL; 8p21
    CMT 2F/ Distal HMN: HSPB1; 7q11
    CMT 2G: See CMT 2P
    CMT 2I: P0; 1q22
    CMT 2J: P0; 1q22
    CMT 2K: GDAP1; 8q21
    CMT 2L: HSPB8; 12q24
    CMT 2M: DNM2; 19p13
    CMT 2N: AARS; 16q22
    CMT 2O: DYNC1H1; 14q32
    CMT 2P: LRSAM1; 9q33
    CMT 2Q: DHTKD1; 10p14
    CMT 2U: MARS; 12q13
    CMT 2V: NAGLU; 17q21
    CMT 2W: HARS; 5q31
    CMT 2Y: VCP; 9p13
    CMT 2Z: MORC2; 22q12
    CMT 2CC: NEFH; 22q12
    CMT 2DD: ATP1A1; 1p13
    CMT 2: TFG; 3q12
    CMT 2: DGAT2; 11q13
    CMT 2: MME; 3q25
    Giant axonal 2: DCAF8; 1q22
    HMSN: BAG3
    HMSN-Proximal: TFG; 3q12
    CMT2 + Pyramidal
      HMSN5: 4q34
      MFN2; 1p36
      KIF5A: 12q13
    HMSN + Optic atrophy
    HMSN + Deafness
      Connexin-31 (GJB3)
      Eye ± Ear dysfunction
    HMSN6A (+ Optic): MFN2; 1p36
    HSMN + Ulcero-mutilation
    HMSN: SPTLC3; 20p12
    HSMN + Ataxia: IFRD1; 7q31
    HMN 5B: BSCL2; 11q13
    CFEOM3: TUBB3; 16q24
    HSAN I
      SPTLC1: 9q22
      SPTLC2: 14q24
      A (B1): Lamin A/C; 1q22
      B (B2): MED25; 19q13.3
      F/Distal HMN: HSPB1; 7q11-q21
      H/Pyramidal signs: 8q21.3
      K/Hoarseness: GDAP1; 8q21
      P: LRSAM1; 9q33
      R: TRIM2; 4q31
      S: IGHMBP2; 11q13
      T: MME; 3q25
      X: SPG11; 15q21
      A2B: MFN2; 1p36
      EE: MPV17; 2p23
      AHNAK2: 14q32
      EGR2; 10q21
      HSJ1/DNAJB2; 2q35
      MCM3AP (GANP): 21q22
      PNKP: 19q13
      PRPH: 12q13
      SACS: 13q12
    Acrodystrophy: ATSV; 2q37
    Andermann: KCC3; 15q13
    Ataxia + Neuropathy
      Cough + Sensory
      Hepato-Cerebellar: SCYL1; 11q13
    Early onset
      CMT: SCO2; 22q13
      Lethal Neonatal
      NBIA2A: PLA2G6; 22q13
      Optic: MFN2; 1p36
      Respiratory failure
        REEP1: 2p11
        MFN2: 1p36
      Severe: NEFL; 8p21
    Episodic: SGPL1; 10q22
    Giant axonal: Gigaxonin; 16q23
    Neuromyotonia: HINT1; 5q31
    Optic neuropathy
      HMSN ± Deaf
      HMSN6B: SLC25A46; 5q22
    Syndromes: HMSN+
      Childhood onset

      1: GJB1 (CX32); Xq13
      6: PDK3; Xp22
      2: Xp22.2
      3: Xq27
      4 (Cowchock): AIFM1; Xq26
      5: PRPS1; Xq22
      Sensory PN + Deaf: Xq23

  Mitochondrial: MT-ATP6
CMT + Intermediate NCV
    CMT-DIA: 10q24
    CMT-IB: DNM2; 19p13
    CMT-DIC: YARS; 1p35
    CMT-DID: P0; 1q22
    CMT-DIE: INF2; 14q32
    CMT-DIF: GNB4; 3q26
    CMT-DIG: NEFL; 8p21
    CMT-X (Semi-dominant)
    CMT 1C: LITAF; 16p13
    CMT 2E: NEFL; 8p21
    Hypomyelination: ARHGEF10; 8p23

    CMT RIA: GDAP1; 8q21.1
    CMT RIB: KARS; 16q23
    CMT RIC: PLEKHG5; 1p36
    CMT RID: COX6A1; 12q24
    CMT XI: DRP2; Xq22

Other related names or disorders

  α-Methylacyl-CoA racemase (AMACR)
  Brachial plexopathy, Hereditary
  Childhood onset neuropathies
  CNS & Cranial nerve disorders
  Complex clinical syndromes
  Congenital Hypomyelinating
    EGR2: 10q21
    P0: 1q22
    PMP-22: 17p11
    ARHGEF10; 8p23
  Connective tissue: EMILIN1; 2p23
  Cowchock: AIFM1; Xq26
  Dejerine-Sottas (HMSN 3)
  Focally folded myelin sheaths
    CMT 4B: MTMR2; 11q23
    CMT 4B2: SBF2; 11p15
    CMT 4E: EGR2; 10q21
    CMT 4F: Periaxin; 19q13
    P0: 1q22
    Juvenile glaucoma
    Motor neuropathies
      Distal (dHMN)
    Sensory neuropathies (HSN; HSAN)
  Metabolic abnormalities
  Minifascicles & Gonadal dysgenesis
    HSN: DHH; 12q12
  Myelin disorders; Recessive
    Brachial plexopathy
    Pressure palsies (HNPP): PMP-22
    Neuropathy: 21q21
  SCA + Neuropathy
  SPG + Neuropathy
  Vertical talus: HOXD10; 2q31
Charcot-Marie-Tooth (CMT)
    Childhood CMT
  Myelin proteins
  External link: Mutation database

Charcot (left) & Babinski
at the Salpêtrière clinic.


  • Hereditary neuropathies: 10 to 40 per 100,000
  • CMT Type 1: 15 per 100,000
  • CMT 1A
    • 10.5 per 100,000
    • 60% to 70% of Demyelinating CMT
    • 40% to 50% of all CMT
  • CMT 2: ? 7 per 100,000
  • Most common: PMP22, GJB1, MPZ, MFN2, GDAP1
Tissue & Functional involvement


R Baloh
Hereditary Neuropathies: Related Molecules

Pathology in hereditary neuropathies: Differential diagnosis 120
Other hereditary motor-sensory neuropathies
Bramwell 1907
Clinical CMT (HMSN): Differential Diagnosis & Associated Features 93

Neuropathy: CMT Genes & Drugs

HMSN types: Comparison of clinical features 36
Disorder Gene Locus Usual onset Early or distinct
CMT1: Dominant; Demyelinating
17p11 1st decade Distal weakness
Commonest form
Absent 15 to 20 M/s
CMT 1B P0 1q22 1st decade Distal weakness
More severe
Absent <20 M/s
CMT 1C LITAF 16p13 2nd decade Distal weakness Reduced 16 to 25 M/s
CMT 1D EGR2 10q21 2nd decade Distal weakness
Absent 26 to 42 M/s
CMT 1F NF-68 8p21 1 to 40 yrs Distal weakness
Reduced Axon loss
CMT 1 Fibulin-5 14q32 3rd to 6th decade Distal weakness Reduced Axon loss
CMT 1 PMP2 8q21 1st & 2nd decade Distal weakness Absent 15 to 22 M/s
CMT X (S-D*) GJB1 Xq13 2nd decade Distal weakness
Hearing loss
Absent distal 25 to 40 M/s
17p11 3rd decade Focal episodic
Normal Entrapments
  (HMSN 3)
2 yrs Severe weakness Absent <10 m/s
CMT DIB DNM2 19p13 1st or 2nd
Distal weakness
25 to 50 m/s
CMT DIE INF2 14q32 1st to 3rd
Distal weakness
Renal (Proteinuria)
23 to 45 m/s
1st to 5th
Distal weakness   15 to 50 m/s
CMT2: Dominant; Axonal
CMT 2A MFN2 1p36 10 yrs Distal weakness
Hearing Δ
Absent distal > 38 M/s
CMT 2B RAB7 3q13 2nd decade Distal weakness
Sensory loss
Absent distal Axon loss
CMT 2C TRPV4 12q24 1st decade Vocal cord &
Distal weakness
Absent > 50 M/s
CMT 2D GARS 7p15 16 to 30 yrs Distal weakness
  Arms > Legs
Reduced Axon loss
CMT 2E NF-68 8p21 1 to 40 yrs Distal weakness Reduced Axon loss
  Distal HMN
HSPB1 7q11 6 to 54 yrs Difficulty walking Reduced ankle Axon loss
CMT 2G   12q12 15 to 25 yrs Distal weakness Reduced 42 to 58 M/s
CMT 2K GDAP1 8q13 Infant Distal weakness
Vocal cord
Early disability
Reduced Axon loss
CMT 2L HSPB8 12q24 15 to 33 yrs Distal weakness Reduced Axon loss
CMT 2M DNM2 19p13 0 to 50 yrs Distal weakness
  Legs > Arms
Reduced Axon loss
CMT 2N AARS 16q22 6 to 54 yrs Distal leg weak
Reduced Axon loss
HMSN-P   3q13 17 to 50 yrs Proximal weakness
Absent Axon loss
HSMN + Ataxia IFRD1 7q31 13 to 27 yrs Gait ataxia Absent Axon loss
CMT 2 P0 P0 1q22 37 to 61 yrs Leg weakness
Pupil or Hearing Δ
Reduced < 38 M/s to
AR-CMT2: Recessive; Axonal
AR-CMT2A Lamin A/C 1q22 2nd decade Distal weakness Reduced Axon loss
AR-CMT2B MED25 19q13 3rd & 4th
Distal weakness Absent distal Axon loss
AR-CMT2 LRSAM1 9q33 2rd to 5th
Distal weakness &
Sensory loss
Absent Axon loss
(CMT 2B5)
NEFL 8p21 < 2 years Severe
Distal weakness &
Sensory loss
Absent Axon loss
AR-CMT2 HSPB1 7q11 1st to 6th decade Distal weakness Reduced Axon loss
Andermann KCC3 15q13 1st decade Hypotonia Absent Mildly
Cowchock AIFM1 Xq26 1st decade Distal weakness
Absent Axon loss
CMT X5 PRPS1 Xq22 8 to 13 yrs Legs
Hearing loss
Optic neuropathy
Reduced Axon loss
CMT4: Recessive; Demyelinating
CMT 4A GDAP1 8q13 Childhood Distal weakness
Vocal cord
Reduced Slow
CMT 4B MTMR2 11q22 2 to 4 yrs Distal & Proximal
Absent Slow
11p15 1st 2 decades Distal weakness
Sensory loss
Absent 15-30 m/s
CMT 4C SH3TC2 5q23 5 to 15 yrs Delayed walking Reduced 14 to 32 M/s
CMT 4D (Lom) NDRG1 8q24 1 to 10 yrs Gait disorder
Hearing Δ
Absent 10 to 20 M/s
CMT 4E EGR2 10q21 Birth Infant hypotonia
Respiratory failure
Absent 9 to 20 M/s
CMT 4F Periaxin 19q13 1 to 3 yrs Motor delay
Sensory loss
Absent Absent
HMSN-Russe (4G) HK1 10q22 8 to 16 yrs Distal leg
CMT 4H FGD4 12q12 10 to 24 mo Walking delay
Severe; Scoliosis
Absent < 15 M/s
CMT 4J FIG4 6q21 Congenital
  to Adult
Proximal &
Distal weakness
Absent 2 to 40 M/s
CMT 4 SURF1 9q34 Childhood Distal weakness &
  sensory loss
Absent 15 to 22 M/s
  (HMSN 3)
2 yrs Severe weakness Absent <10 M/s
Birth Severe weakness Absent <10 M/s
CCFDN CTDP1 18q23 1st or 2nd
Distal leg weak
Reduced 20 to 34 M/s
* Semi-Dominant

External links

Hereditary Motor-Sensory Neuropathy (HMSN) Syndromes


  PMP 22 ; Chromosome 17p12; Dominant

PMP-22 mutation types
    Contiguous gene (YUHAL)
  Homozygous (Duplication)
CMT 1E (Deafness)
  Clinical-Gene relations
  Gene mutations

Also see: HNPP

PMP-22 Duplication

Chaddock 1900

CMT IB + Other P0 mutation syndromes 61

  P0 protein (MPZ) ; Chromosome 1q23.3; Often Dominant or de novo

P0: Genetic features
P0 protein
P0 Clinical syndromes
  CMT 1B: Dominant; Demyelinating
  CMT 1B (Roussy-Levy): Dominant; Demyelinating
  CMT 1B: Dominant; Demyelinating; Pupils; Early onset
  CMT 1E: Dominant; Demyelinating, Hearing loss
  CMT 2I: Dominant; Axonal
  CMT 2J: Dominant; Axonal; Pupil disorders; Hearing loss
  CMT-DID: Dominant; Intermediate nerve conductions
  Congenital: Recessive or Dominant; Hypomyelinating
  Dejerine-Sottas: Dominant or Recessive; Demyelinating
  Steroid responsive, Late-onset: Dominant; Demyelinating
  Adult onset (Axonal)
  Hypertrophic radiculopathy
  P0 variant syndromes


CMT 1C 20

  Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF; SIMPLE; EET1; PIG7) ; Chromosome 16p13.13; Dominant

EGR2 mutations: CMT 1D & Other phenotypes

  EGR2 (Krox20) ; Chromosome 10q21.3; Dominant or Recessive

Hereditary Neuropathies (CMT 1 or D-HMN) ± Macular Degeneration & Hyperelastic Skin (HNARMD) 91

  Fibulin-5 (FBLN5) ; Chromosome 14q32.12 Dominant

CMT 1G 129

  Peripheral myelin protein 2 (PMP2) ; Chromosome 8q21.13; Dominant or Sporadic

CMT: X-linked

Type 1
Type 2
Type 3
Type 4 (Cowchock)
Type 5
Pyramidal signs



General features

CMT 2A: General

  Kinesin family member 1Bβ (KIF1B) ; Chromosome 1p36.22; Dominant

From: B Baloh MD

  Mitofusin 2 (MFN2; KIAA0214) ; Chromosome 1p36.22; Dominant, Semi-Dominant or Recessive

  RAB7 ; Chromosome 3q21.3; Dominant

  • CMT 2C (HMSN 2C) 27
      TRPV4 ; Chromosome 12q24.11: Dominant

    CMT 2D
      Glycyl tRNA Synthetase (GARS) ; Chromosome 7p14.3; Dominant

    CMT 1F 39
      Neurofilament light chain (NEFL) ; Chromosome 8p21.2; Dominant or Sporadic CMT 2E 4
      Neurofilament light chain (NEFL) ; Chromosome 8p21.2; Dominant
    AR-CMT (CMT 2B5): Severe, Early onset 78
      Neurofilament light chain (NEFL) ; Chromosome 8p21.2; Recessive

    CMT 2F/ Distal HMN 19
      Heat-shock 27-kD protein 1 (HSPB1; HSP 27) ; Chromosome 7q11.23; Dominant or Recessive

    CMT 2L 47
      Heat-shock 22-kD protein 8 (HSPB8) ; Chromosome 12q24.3; Dominant

    CMT 2N 81
      Alanyl-tRNA Synthetase (AARS) ; Chromosome 16q22.1; Dominant

    CMT 2O 96
      Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) ; Chromosome 14q32.31; Dominant

    CMT 2Q 108
      2-Oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrial, Probable (DHTKD1) ; Chromosome 10p14; Dominant

    Charcot-Marie-Tooth disease, Recessive Intermediate D (CMTRID) 123
      COX6A1 ; Chromosome 12q24.31; Recessive


    CMT 2-P0

    Hereditary Sensory-Motor Neuropathy with Ataxia (SMNA) 26
      Interferon-related developmental regulator gene 1 (IFRD1) ; Chromosome 7q31.1; Dominant

    CMT with Intermediate NCV (DI-CMT) 17

    DI-CMT, Type A (CMTDIA)
      Chromosome 10q24.1-q25.1; Dominant

    DI-CMT, Type B (CMTDIB)
      Dynamin 2 (DNM2) ; Chromosome 19p13.2; Dominant

    DI-CMT, Type C (CMTDIC) 43
      Tyrosyl-tRNA synthetase (YARS) ; Chromosome 1p35.1; Dominant

    DI-CMT, Type E (CMT-DIE): CMT, Intermediate with Glomerulopathy 101
      Inverted formin 2 (INF2; c14orf173) ; Chromosome 14q32.33; Dominant or Sporadic

    DI-CMT, Type F (CMT-DIF) 113
      Guanine nucleotide-binding protein, β4 (GNB4) ; Chromosome 3q26.33; Dominant

    Other CMT disorders with intermediate NCV

    Recessive, Axonal CMT

    AR-CMT2A: Lamin A/C; 1q22
    AR-CMT2B: MED25; 19q13.3
    AR-CMT2 + Hoarseness (CMT 2K): GDAP1; 8q21
    AR-CMT2, Severe & Early onset: NEFL; 8p21
    AR-CMT2/Distal HMN: HSPB1; 7q11-q21
    AR-CMT2: LRSAM1; 9q33
    AR-CMT2-Ouvrier: Early childhood onset
    AR-CMT2 + Neuromyotonia: HINT1; 5q31
    Andermann (Corpus callosum Δ): 15q13
    CMT X-linked
    HMSN + CNS: Heterogeneous
    Giant axonal neuropathy: Gigaxonin; 16q24
    HMSN + Deafness
    HMSN + Optic neuropathy ± Deafness
    Lethal Neonatal
    Neuroaxonal dystrophy

    Axonal CMT (AR-CMT2A; CMT2B1) 1
      Lamin A/C ; Chromosome 1q22; Recessive

    Axonal CMT (AR-CMT2B; CMT2B2) 12
      MED25 (ARC92; ACID1) ; Chromosome 19q13.33; Recessive

    CMT 2K 23
      Ganglioside-induced differentiation-associated protein 1 (GDAP1) ; Chromosome 8q21.11; Recessive or Dominant

    GDAP1 CMT Variants
        Recessive (AR-CMT 2K)
        Recessive, Mild
        Dominant (CMT 2K)
        Recessive, Type A (CMT RIA)
        Recessive, (CMT 4A)

    Axonal CMT (AR-CMT): Ouvrier type
      Autosomal Recessive or Semi-Dominant

    Axonal CMT with pyramidal involvement (AR-CMT2C; CMT4C2; CMT 2H) 14
      Chromosome 8q21.3; Recessive

    HMSN with Intermediate NCV, X-linked (CMT XI) 128
      Dystrophin-related protein 2 (DRP2) ; Chromosome Xq22.1; Recessive

    Hereditary Ulcero-mutilating Sensory > Motor Neuropathy, Recessive (HSAN IIC; HSN2C) 94
      Axonal transporter of synaptic vesicles (KIF1A; ATSV) ; Chromosome 2q37.3; Recessive

    Axonal CMT (CMT2) with Acrodystrophy, Recessive
      Recessive 8

    Axonal CMT (CMT2P), Recessive
      Leucine-rich repeat- and sterile alpha motif-containing 1 (LRSAM1) ; Chromosome 9q33.3; Recessive 90 or Dominant 99

    Axonal CMT2, Recessive + Neuromyotonia (ARAN-NM; AR-CMT2 + Neuromyotonia; NMAN) 106
      Histidine triad nucleotide-binding protein 1 (HINT1) ; Chromosome 5q31.1; Recessive
    • Nosology
    • Epidemiology
      • 11% of AR-CMT2 families: > 60 families
      • Common in
        • Eastern Europe & Czech: Arg37Pro founder mutation; Carrier frequency up to 1/67
        • Portugal Roma & Italy: H112N
    • Genetics: Mutations
      • Missense
      • Loss of function
      • Glu34Lys; Arg37Pro; Q62X; C84R; G89V; G93D; H112N; W123X; c.148_149delAC
    • HINT1 protein
      • Histidine triad family
      • Subunit structure: Homodimer
      • Interacts with: CDK7
      • Subcellular location: Cytoplasm, Nucleus
      • Ubiquitously expressed
      • Purine phosphoramidase
        • Hydrolyzes adenosine 5'-monophosphoramidate substrates
        • Preferentially hydrolyses adenosine derivatives with a single phosphate, including phosphoramidates
      • Binds to lysyl-tRNA synthetase (KARS; LysRS)
      • Transcription factors regulated by HINT1
        • MITF , USF2 , Pontin (RUVBL1) , Reptin (RUVBL2)
        • Inhibits activator protein-1 (AP1; JUN) transcription factor by binding to POSH-JNK2 complex
      • Interacts with the μ-opioid receptor (MOR), major molecular target for morphine analgesia
    • Clinical
      • General: Motor > Sensory
      • Onset
        • Age: Often childhood; Range 3 to 28 years
        • Gait imbalance
      • Weakness
        • Distal
        • Legs > Hands (Finger extensors)
        • May be asymmetric
      • Muscle wasting: Distal; Legs & Hands
      • Neuromyotonia
        • Rest: Myokymia
        • Legs: Stiffness
        • Cramps & Fasciculations: Arms & Legs
        • Myotonia
          • Action, Not Percussion
          • Worse in Cold
          • Increased with action
          • Especially hands & grip
        • Frequency: 70% to 80%
        • Increased with nerve ischemia
      • Sensory loss: Some patients
      • Tendon reflexes: Reduced or Absent; Worse with disease progression
      • Joints
        • Hands: Flexion contractures with disease progression
        • Feet: Deformities
          • Pes cavus, equinovarus, cavovarus or Achilles tendon shortening
          • Toe contractures
        • Scoliosis (33%)
      • Course: Progressive; Most remain ambulatory > 60 years
    • Laboratory
      • Sensory nerve biopsy: Axon loss
      • EMG
        • Neuromyotonia
          • Spontaneous peripheral nerve discharges
            • Often increased by: Voluntary muscle contraction
          • Electrical activity
            • Enhanced by: Nerve ischaemia,
            • Not by: Mechanical or Rlectrical stimulation
        • Neurogenic changes: Distal > Proximal
      • NCV
        • Axon loss
          • Motor: 100%
          • Sensory: 65%
        • Conduction velocities: Normal
      • Serum CK: Normal to 1300; High in 33%
      • Sural nerve biopsy: Axon loss
    • Heterozygous carriers: Normal

    NMAN: Leg wasting, Distal

    Axonal CMT2, Recessive, Early-onset 115
      Tripartite motif-containing protein 2 (TRIM2) ; Chromosome 4q31.3; Recessive

    AR-CMT2T: Axonal CMT2, Recessive, Adult onset 133
      Membrane metalloendopeptidase (MME; CD10; CALLA; Neprilysin; NEP) ; Chromosome 3q25.2; Recessive
    AR-CMT2 + Intellectual Disability (PNRIID) 138
      Minichromosome maintenance 3-associated protein (MCM3AP; GANP) ; Chromosome 21q22.3; Recessive
    AR-CMT2 147
      AHNAK Nucleoprotein 2 (AHNAK2) ; Chromosome 14q32; Recessive
    Episodic Axonal Recessive Neuropathy 137
      Sphingosine 1-phosphate lyase (SGPL1) ; Chromosome 10q22.1; Recessive

    HMSN III (Dejerine-Sottas) 32


    Dejerine & Sottas 1893

    Hereditary Liability to Pressure Palsies (HNPP)

    PMP-22 mutations
    KARS mutations

    HNPP: PMP-22 Genetics
      PMP-22 deletion; Chromosome 17p12; Dominant

    HNPP-PMP22: Clinical features 44 HNPP: Laboratory features
    Charcot-Marie-Tooth disease, Recessive Intermediate B (CMTRIB) 88
      Lysyl-tRNA Synthetase (KARS) ; Chromosome 16q23.1; Recessive or Dominant

    CMT 4

    General features

    CMT 4A
      Ganglioside-induced differentiation-associated protein 1 (GDAP1) ; Chromosome 8q21.11; Recessive

    HMSN with focally folded myelin sheaths (CMT 4B)

      CMT 4B1 (CMT 4B)
        Myotubularin-related protein-2 (MTMR2) ; Chromosome 11q21; Recessive

      CMT 4B2 2
        SET binding factor 2 (SBF2) (MTMR13) ; Chromosome 11p15.4; Recessive   HMSN with focally folded myelin sheaths: With juvenile-onset Glaucoma 6
        SET binding factor 2 (SBF2) (MTMR13) ; Chromosome 11p15.4; Recessive

      CMT 4B3 with Focally folded myelin 117
        SET binding factor 1 (SBF1) (MTMR5) ; Chromosome 22q13.33; Recessive

      HMSN with focally folded myelin sheaths: Dominant
        P0 protein; Chromosome 1q23.3; Dominant
        Additional loci

      HMSN with focally folded myelin sheaths: Additional locus

    CMT 4C
      SH3 domain and tetratricopeptide repeat domain 2 (SH3TC2; KIAA1985) ; Chromosome 5q32; Recessive

    CMT 4D: HMSN (Demyelinating) & Hearing loss (Lom type)
      N-myc Downstream-Regulated Gene 1 (NDRG1) ; Chromosome 8q24.22; Recessive

    CMT 4F 3
      Periaxin (PRX) ; Chromosome 19q13.2; Recessive

    HMSN-Russe (HMSNR; CMT 4G) 5
      Hexokinase 1 (HK1) ; Chromosome 10q22.1; Recessive

    CMT 4H 52
      frabin/FGD4 ; Chromosome 12p11.21; Recessive

    CMT 4J 69
      FIG4 ; Chromosome 6q21; Recessive

    HMSN with CNS or Cranial nerve involvement

    Dominant, Axonal
    Dominant, Demyelinating
    Recessive, Axonal
    Recessive, Demyelinating
    X-linked, Demyelinating

    HMSN with CNS or Cranial nerve: Dominant, Demyelinating

    HMSN with Systemic, CNS or Cranial nerve Disorders: Dominant, Axonal

    HMSN with CNS or Cranial nerve: Recessive, Axonal neuropathy

    HMSN with CNS or Cranial nerve: Recessive, Demyelinating

    REFSUM SYNDROMES (Peroxisome Biogenesis Disorders; Zellweger syndromes)

    HMSN with CNS or Cranial nerve: X-linked, Demyelinating

    HMSN with pyramidal signs & cerebral white matter lesions 40

    Hereditary Neuropathies - Other

    α-Methylacyl-CoA racemase (AMACR) deficiency
      AMACR ; Chromosome 5p13.2; Recessive
    HMSN with Minifascicle Formation & 46XY Pure Gonadal Dysgenesis 25
      desert hedgehog (DHH) ; Chromosome 12q13.12; Sporadic (Recessive)
    HMSN with Congenital vertical talus 49
      HOXD10 ; Chromosome 2q31.1; Dominant
    Hereditary Recurrent Neuropathy 122
      Chromosome 21q21.1–q21.3; Dominant
    CMT 2W: Peripheral neuropathy, Hereditary 105
      Histidyl-tRNA synthetase (HARS) ; Chromosome 5q31.3; Dominant or Sporadic

    CMT 2U: Peripheral neuropathy, Sensory-Motor 116
      Methionyl-tRNA synthetase (MARS) ; Chromosome 12q13.3; Dominant
    CMT 2Z: Peripheral neuropathy, Sensory-Motor 131
      MORC family CW-type zinc finger protein 2 (MORC2) ; Chromosome 22q12.2; Dominant

    CMT 2: Peripheral neuropathy, Early onset + Sensory Ataxia 132
      Diacylglycerol O-Acyltransferase 2 (DGAT2) ; Chromosome 11q13.5; Dominant

    CMT 2: Peripheral neuropathy, Motor + Sensory 139
      ATPase, Na+/K+ transporting, alpha-1 polypeptide (ATP1A1) ; Chromosome 1p13.1; Dominant
    Also see: Childhood onset neuropathies
    Patient information
    Support groups

    Return to Polyneuropathy Index
    Return to Neuromuscular home page

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    Illustration by J. Kwon, MD