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Charcot–Marie–Tooth Association
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CMT4

Recessive Demyelinating Types of CMT

All Type 4 instances of CMT are inherited in an autosomal recessive pattern (see inheritance) and are rare in the United States (~5% of cases). Type 4 is also typically demyelinating. They have various presentations, with some being mild and some severe. These disorders may also have symptoms in other areas of the body, such as cataracts and deafness.

What causes CMT4

CMT4 is caused by a variety of gene mutations inherited in an autosomal recessive pattern. The person with CMT4 would have two copies of the affected gene to develop symptoms. These genes are not located on the chromosomes associated with determining biological sex. Both parents of the person with CMT4 are “carriers” of the affected gene. The parent carrier has one copy of affected gene with recessive inheritance and will not exhibit symptoms of CMT4.

Mutated genes related to Type 4 include:

  • CMT4A – Ganglioside-induced differentiation-associated protein 1 (GDAP1)
  • CMT4B1 – Myotubularin related protein 2 (MTMR2)
  • CMT4B2 – SET binding factor 2 (SBF2/MTMR13)
  • CMT4B3 – SET binding factor 1 (SBF1/MTMR5)
  • CMT4C – SH3 domain and tetratricopeptide repeat-containing protein 2 (SH3TC2/KIAA1985)
  • CMT4D – N-myc downstream regulated 1 (NDRG1)
  • CMT4E or CHN-1 – Early growth response 2 (EGR2/Krox20)
  • CMT4F – Periaxin (PRX)
  • CMT4G or HMSN-Russe Type (HMSNR) – Hexokinase 1 (HK1)
  • CMT4H – FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4)
  • CMT4J – Polyphosphoinositide phosphatase (FIG4)
  • CMT4K – Surfeit locus protein 1 (SURF1)

What are the Symptoms of CMT4

The symptoms of people with CMT4 usually progress faster than those of people with autosomal dominant CMT types. Signs and symptoms include a broad spectrum, but MAY include:

  • pes cavus (high arch) and hammertoes
  • pes equino-varus (claw-like hands)
  • spinal abnormalities
  • cataracts
  • deafness
  • High or flat arches
  • Respiratory problems due to progression of disease/involvement of breathing muscles and diaphragm weakness
  • Bony or joint abnormalities
  • CNS involvement (issues with cognition or other brain functions)

When do symptoms of CMT4 start?

The age of onset typically occurs during early infancy (before the age of 3), but can also begin later in life.

Simply CMT