Charcot-Marie-Tooth (CMT) history

First identified in 1886, Charcot-Marie-Tooth disease (CMT) is an inherited neurological disorder that affects both motor and sensory nerves. It currently impacts approximately 1 in 2,500 people, of all genders and ethnicities. CMT is also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, which are a group of disorders that affect peripheral nerves and the muscles attached to the peripheral nervous system. Peripheral nerves are found outside the brain and spinal cord; their job is to supply the muscles and sensory organs in the limbs with the messages needed to operate correctly. There are many subtypes of CMT, including variants in at least 80 genes that cause the different subtypes of CMT. Symptoms and disease management for each subtype of CMT vary.

Type CMT4 history

All subtypes of CMT4 are inherited in an autosomal pattern. Autosomal recessive describes one of several ways that a disorder or disease is passed down through families. An autosomal recessive disorder occurs when two copies of an abnormal gene are passed from each parent to the child.

CMT is further classified based on the pathogenic variant involved — for instance, CMT4A, CMT4B, etc.

Type CMT4J history

CMT4J is a very rare subtype of CMT. It accounts for approximately one quarter of the 4% of CMT cases that are recessive. First described in scientific literature 100 years earlier, the gene was not identified until 2007, when it was found in patients previously diagnosed with unknown CMT variants. In 2011, a study was conducted that identified almost three times more patients living with 4J. Today, even more patients have been diagnosed with CMT4J outside of this study through the efforts of CureCMT4J, a family foundation and advocacy organization.

Reported cases of CMT4J total approximately three dozen worldwide and make up less than 1% of all CMT cases. Healthy carriers of the FIG4 gene are more common; the carrier rate of the FIG4 gene among northern Europeans is 1 in 1,000.

It is common for individuals to receive misdiagnoses prior to learning that they are living with CMT4J. People living with CMT4J are commonly misdiagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), multiple sclerosis (MS), Guillain-Barré Syndrome (GBS), and amyotrophic lateral sclerosis (ALS), as well as other CMT and neuromuscular diseases, with the primary symptom being muscle weakness due to issues with the muscle fiber (myopathies).

Sources:

  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 on June 26, 2019, from link.
  2. Field research conducted by Neurogene and Ten Bridge Communications, July 2019.
  3. Charcot-Marie-Tooth disease. (2018, October). Retrieved June 26, 2019, from link.
  4. Charcot-Marie-Tooth Disease Fact Sheet. (2019, May 13). Retrieved June 26, 2019, from link.
  5. Kushimura, Y., Azuma, Y., Mizuta, I., Muraoka, Y., Kyotani, A., Yoshida, H., Tokuda, T., Mizuno, T., Yamaguchi, M. (2018, July 4). Loss-of-function mutation in Hippo suppressed enlargement of lysosomes and neurodegeneration caused by dFIG4 knockdown. NeuroReport. 29(10), 856-862. doi:10.1097/WNR.0000000000001044. Retrieved September 12, 2019, from link.
  6. Lewis, R. (2017, February 23). Rare Disease Day 2017: Talia’s Story [Web log post]. Retrieved June 26, 2019, from link.
  7. Martyn, C., & Li, J. (2013, Feb.). Fig4 Deficiency: a newly emerged lysosomal storage disorder? Progress in Neurobiology. doi:10.1016/j.pneurobio.2012.11.001. Retrieved September 12, 2019, from link.
  8. Rajabelly, Y., Adams, D., Latour, P., Attarian, S. (2016, March 23). Hereditary and inflammatory neuropathies: a review of reported associations, mimics, and misdiagnoses. JNNP Online First. BMJ. doi:10.1136/jnnp-2015-310835. Retrieved September 12, 2019, from link.