Charcot-Marie-Tooth disease CMT

Synonyms:
  • Hereditary Motor and Sensory Neuropathy HMSN
  • Now the whole group is called Charcot-Marie-Tooth disease CMT

Diagnosis:

Clinical +electrodiagnostics (EMG/NCS) +Genetic testing:

Clinical features:

Abnormal LMN features: weakness
Atrophy: champagne-glass legs, stork legs
Deformity: claw toe, Friedreich’s foot, kyphoscoliosis
Sensory features: loss of vibration and later on loss of proprioception
Palpable nerves

Genetics:

CMT1 a.k.a. HMSN1 a.k.a. Charcot-Marie-Tooth CMT disease a.k.a. peroneal muscular artrophy, demyelinating:
CMT1 Autosomal dominant forms:

  • CMT1A: PMP22 gene chr. 17p11.2, peripheral myelin protein-22 PMP22
  • CMT1B: MPZ gene chr. 1q22, protein= myelin protein zero MPZ
  • CMT1C: LITAF gene chr. 16p13.3-p12
  • CMT1D: early growth response EGR2 gene chr. 10q21.1-q22.1,
  • CMT1E:
  • CMT1F: NEFL gene chr. 8p21, protein= Neurofilament light chain,

Dejerine-Sottas disease DSD a.k.a. HMSN3:

  • DSD A AD (AR) 17p11.2-12, protein PMP-22
  • DSD B AD (AR) 1q22-q23
  • DSD C AD 10q21-q22, Gene= EGR2

CMT1 AR: autosomal recessive forms (formerly CMT4):

  • CMT1 ARA (CMT4A) chr. 8q13 – 21.1. Gene= GDAP1
  • CMT1 ARB1 (CMT4B1) chr. 11q22. Gene=  MTMR2
  • CMT1 ARB2 (CMT4B2) chr. 11p15. Gene=  MTMR13
  • CMT1 ARC (CMT 4C) chr. 5q23-q33. Gene= KIAA1985
  • CMT1 ARD (CMT4D) chr. 8q24. Gene=  NDRG1
  • CMT1 ARE (CCFDN) chr. 18q
  • CMT1 ARF (CMT4F) chr. 19q13.1-13.3. Gene=  Periaxin
  • CMT1 ARG (HMSNR) chr. 10q22-q

CMT 1X i.e. CMT type 1 X-linked, demyelinating, X-linked. Xq13.1
CMT2 a.k.a. HMSN2, axonal:

  • CMT2 AD, Autosomal dominant forms:
    • CMT 2A AD, chr. 1p35. Gene=KIF1B. Protein= GTPase mitofusin 2
    • CMT 2B AD, chr.  3q13 – q22. Gene= RAB7
    • CMT 2C AD, chr.  12q23 – q24
    • CMT 2D AD, chr.  7p14. Gene= GARS
    • CMT2E AD: NEFL gene chr. 8p21, protein= Neurofilament light chain,
    • CMT 2F AD, chr.  7q11-q21. Gene= HSP 27
    • CMT 2G AD, chr.  12q12-q13.3
    • CMT 2L AD, chr.  12q24. Gene= HSP 22
    • CMT 2 AD, chr. 1q22-q23
  • CMT2 AR, autosomal recessive forms:
    • CMT2 AR, chr. 1q21.2 – 21.3. Gene= LMNA
    • CMT2 AR, chr. 19q13.1
    • CMT2 AR, chr. 8q21. Gene= GDAP1 3.
  • CMT 2X i.e. CMT type 2 X-linked, axonal, X-linked. Xq24-26

Pathology, nerve biopsy:

CMT1, CMTX:

  • Loss of myelinated fibres, affects all fascicles to the same extent
  • Onion bulb formation: demyelination and remyelination, except in young children
  • Increased size of fascicles

CMT2:

  • Nonspecific. Loss of axons

Investigations to consider:

EMG, NCS: axonal vs. demyelinating
Appropriate genetic testing

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