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Charcot–Marie–Tooth Association
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CMT2

Axonal Types of CMT

CMT Type 2 represents axonal forms of Charcot-Marie-Tooth disease that are dominantly inherited and make up about one-third of all dominant CMT cases. Patients with Type 2 have a wider age range for onset of the disorder and more variation in degree of disability.

What causes CMT2

CMT2 is caused by a variety of gene mutations. The gene that is mutated determines the subtype of CMT2 that a person has. Mutations that can cause type 2 include:

  • CMT2A, CMT2A2B, CMT2B4, HMSN6A – Mitofusin 2 (MFN2)
  • CMT2B – Members RAS oncogene family (RAB7 or RAB7A)
  • CMT2B1 – Lamin A/C (LMNA)
  • CMT2B2 – Polynucleotide Kinase-Phosphatase (PNKP)
  • CMT2B3, CMT2K – Ganglioside-induced differentiation-associated protein 1 (GDAP1)
  • CMT2B5, CMT2E – Neurofilament light polypeptide (NEFL)
  • CMT2C – TRP superfamily of cation channels (TRPV4)
  • CMT2CC – Neurofilament heavy polypeptide (NEFH)
  • CMT2D – Glycyl-tRNA synthetase (GARS)
  • CMT2DD – ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1)
  • CMT2EE – mitochondrial inner membrane protein (MPV17)
  • CMT2F – Heat shock 27-kD protein 1 (HSPB1/HSP27)
  • CMT2FF – Cell adhesion molecule 3 gene (CADM3)
  • CMT2GG (formerly called CMTDIA) – Golgi-specific brefeldin-A resistance factor 1 gene (GBF1)
  • CMT2HH – Jagged 1 gene (JAG1/JAGL1)
  • CMT2I, CMT2J – Myelin protein zero (MPZ/P0)
  • CMT2L – Heat-shock 22-KD protein 8 (HSPB8/HSP22)
  • CMT2M – Dynamin 2 (DNM2)
  • CMT2N – Alanyl-tRNA synthetase (AARS1/AARS/ALARS)
  • CMT2O – Dynein cytoplasmic 1 heavy chain 1 (DYNC1H1)
  • CMT2P – Leucine rich repeat and sterile alpha motif containing 1 (LRSAM1)
  • CMT2Q – Dehydrogenase E1 and transketolase domain containing protein 1 (DHTKD1)
  • CMT2R – Tripartite motif containing protein 2 (TRIM2)
  • CMT2S – Immunoglobulin mu DNA binding protein 2 (IGHMBP2)
  • CMT2T – Membrane metalloendopeptidase (MME)
  • CMT2U – Methionyl-tRNA synthetase (MARS1/MARS)
  • CMT2V – N-acetyl-alpha-glucosaminidase (NAGLU)
  • CMT2W – Histidyl-tRNA synthetase (HARS1/HARS)
  • CMT2X – Spatacsin (SPG11)
  • CMT2Y – Valosin containing protein (VCP)
  • CMT2Z – MORC family CW-type zinc finger protein 2 (MORC2)
  • HMSN-Okinawa Type – Protein TFG (TRK-fused gene protein) (TFG)
  • MYH14-dHMN – Myosin, heavy chain 14 (MYH14)

What are the Symptoms of CMT2

CMT2 patients show little if any slowing in their nerve conductions, and biopsies show the loss of myelinated axons but little segmental demyelination/remyelination. The clinical presentation is similar to Type 1: distal weakness, muscle atrophy, sensory loss and foot deformities. They are slightly more likely to maintain their deep tendon reflexes.

When do symptoms of CMT2 start?

The age of onset varies from childhood to 60 years of age, even within families. Whereas the original descriptions of CMT2 identified patients affected at an older than typical CMT1 patients, the mutations that cause these late onset cases have proven difficult to identify. Rather, MFN2 mutations, the commonest cause of CMT2 identified to date, cause an axonal neuropathy that mainly has an onset in childhood. All other types of CMT2 are rare; many more genetic causes remain to be discovered.

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