How CMT4J Affects the Body

The severity and timing of when signs and symptoms of CMT4J begin to show in individuals can vary. Some patients show mild signs, while others have a more severe disability that requires more support. CMT4J mainly causes problems with motor skills, such as weakness in the limbs and muscles. Individuals with CMT4J gradually or rapidly lose both gross motor control and fine motor control.

Living CMT4J | Signs and Symptoms Illustration

Science Behind CMT4J

CMT4J affects both motor and sensory nerves, so understanding how the nervous system functions is essential. The nervous system consists of both motor neurons and sensory neurons. One set of nerves delivers messages from the brain to the rest of the body, and the other brings messages from the rest of the body back to the brain.

Motor neurons send messages from the brain through the spinal cord to the lower muscles of the body. Sensory neurons send messages from the sensory input to the spinal cord upward to the brain. The peripheral nervous system (the nervous system outside of the brain and spinal cord) affects both motor and sensory nerve fibers. These nerves have an inner coating, the axon core, which is wrapped with a protective insulation called the myelin sheath. The myelin sheath’s job is to protect the axon and speed transmission of signals through the nerves.

In individuals living with CMT, these nerves are damaged due to mutated genes that result in both motor symptoms (weakness and muscle wasting) and sensory symptoms (numbness).

Living CMT4J | Science Behind CMT4J



All subtypes of CMT4 are inherited in an autosomal recessive pattern. Autosomal recessive describes one of several ways that a disorder or disease is passed down through families. An autosomal recessive disorder occurs when a child inherits two copies of an abnormal gene, one from the mother and one from the father. The biological parents often have no symptoms of disease because the one functional gene is able to compensate for the defective gene. Two healthy people, who are carriers, can have multiple children with a genetic disorder even though they do not show symptoms themselves.

In the case of CMT4J, a variant in the FIG4 gene must be inherited from both parents for a child to inherit the CMT4J disease.

Healthy FIG4 Gene

When functioning normally, FIG4 encodes a protein that aids in the survival of neurons and regulates the transport of waste within the cells.

Living CMT4J |

CMT4J Gene

When there is a FIG4 variant present, the body’s ability to move waste through cells is impaired and waste builds up. This buildup of waste slows the nerves’ ability to do their job of sending messages and leads to nerve damage, classifying CMT4J as a demyelinating neuropathy. Demyelination leads to weakness and sometimes numbness or pain.

Living CMT4J | Neurogene Illustration


  1. Nicholson, G., Lenk, G. M., Reddel, S. W., Grant, A. E., Towne, C. F., Ferguson, C. J., … Meisler, M. H. (2011). Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P₂ phosphatase FIG4. Brain: a journal of neurology134(Pt 7), 1959–1971. doi:10.1093/brain/awr148. Retrieved June 26, 2019, from link.
  2. Field research conducted by Neurogene and Ten Bridge Communications, July 2019.
  3. Novais, E. N., Bixby, S. D., Rennick, J., Carry, P. M., Kim, Y. J., & Millis, M. B. (2014). Hip dysplasia is more severe in Charcot-Marie-Tooth disease than in developmental dysplasia of the hip. Clinical orthopaedics and related research472(2), 665–673. doi:10.1007/s11999-013-3127-z. Retrieved June 26, 2019, from link.
  4. Hatakeyama, S., Suzuki, J., Murukami, T., Nagaoka, T., Suzuki, K., Sakamato, K., … Uchigata, M. (2000). [Respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease: A case report]. Journal of the Japanese Respiratory Society, 38(8), 637-641. Retrieved June 26, 2019, from link.
  5. Bharadwaj, R., Cunningham, K. M., Zhang, K., & Lloyd, T. E. (2015). FIG4 regulates lysosome membrane homeostasis independent of phosphatase function. Human Molecular Genetics, 25(4), 681-692. doi:10.1093/hmg/ddv505. Retrieved September 24, 2019, from link.
  6. Haidar, M., & Timmerman, V. (2017). Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies. Frontiers in Molecular Neuroscience, 10. doi:10.3389/fnmol.2017.00143. Retrieved September 24, 2019, from link.
  7. Types of CMT. (n.d.). Retrieved June 26, 2019, from link.
  8. Fliesler, N. (2017, March 6). With no time to lose, parents drive CMT4J gene therapy forward. Retrieved June 26, 2019, from link.
  9. Lewis, R. (2017, February 23). Rare Disease Day 2017: Talia’s Story [Web log post]. Retrieved June 26, 2019, from link.
  10. Li, J. (1993). Charcot-Marie-Tooth Neuropathy Type 4J. Retrieved June 26, 2019, from link.
  11. About CMT4J. (n.d.). Retrieved June 26, 2019, from link.
  12. Orengo, J. P., Khemani, P., Day, J. W., Li, J., & Siskind, C. E. (2018). Charcot Marie Tooth disease type 4J with complex central nervous system features. Annals of Clinical and Translational Neurology, 5. doi:10.1002/acn3.525. Retrieved on June 26, 2019, from link.