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