CHARCOT-MARIE TOOTH DISEASE

Disease

Brief Summary

Charcot-Marie Tooth Disease (CMT) is manifested as a group of inherited peripheral nerve problems. Despite being a neurological disorder, it is not life-threatening and it does not affect the brain. Affected individuals mostly have smaller, weaker muscles. Through stem cell and physiotherapy, the symptoms of this disease can be alleviated. CMT is also known as hereditary motor and sensory neuropathy.

Person affected by Charcot-Marie-Tooth Disease

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Source

Frequency

Charcot-Marie-Tooth disease is the most common inherited disorder that involves the peripheral nerves. It occurs in populations worldwide with a prevalence of about 1 in 3,300 individuals.

Inheritance

Charcot-Marie-Tooth disease has different modes of inheritance, including autosomal dominant, autosomal recessive, and rarely, X-linked. The most common mode of inheritance is autosomal dominant, where one copy of the mutated gene is sufficient to cause the disease. Autosomal recessive inheritance requires both copies of the gene to be mutated, and X-linked inheritance is rare and affects males differently from females

History of Disease

In 1886, Jean-Martin Charcot and Pierre Marie of France, and Howard Henry Tooth of the United Kingdom first reported Charcot-Marie-Tooth disease (CMT) and was described as a spectrum of nerve disorders. Hoffman during 1912 distinguished an instance of peroneal solid decay with thickened nerves and was alluded to as Hoffman sickness and later named Charcot-Marie-Tooth-Hoffman illness. In the year of 1968, CMT illness was partitioned into two kinds, respectively, CMT 1 and CMT 2, basing on pathologic and physiologic rules.

Brief Summary

History of Disease

Pathogenesis

Type X Charcot-Marie-Tooth sickness (CMTX) is brought about by mutations in the GJB1 gene, located on the X-chromosome that ciphers protein connexin-32 (gap junction beta 1). CMTX condition is considered as X-linked in which it causes the mutations on the X chromosome. CMTX is acquired in a X-linked dominant parent such inheritance is possible in the event that if one dominant duplicate of the altered gene is adequate to cause the disease.

Source

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Mutated chromosome by CMT Disease

Symptoms

high foot arches

difficulty lifting your foot at the ankle (footdrop)

curled toes (hammertoes)

awkward or higher than normal step (gait)

Social Concerns

In an investigation of 80 individuals living with CMT, it was found that there is a downturn with individuals living with the condition. Living with CMT can be debilitating, disappointing, and overpowering, and may prompt misery, forlornness, outrage, and dread.

Clinical Trials

Treatment

Different methods are used by scientists which contributes to creating available clinical medication for CMT disease, such as physiotherapy and stem cell treatment. Physiotherapy treatment reduces the risk of muscle contractures, thus, utilizing physical techniques, such as massage and manipulation, that stimulate healing and well being. Stem cell treatment includes introducing lively cells that advances nerve recovery.

Source

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Treatment for CMT Disease

Expert Directory

Dr. Martha Bolanos

Pediatrician - Neurologist

Location:

Metropolitan Medical Center

Binondo, Manila

Clinical Trials

Title:

International, Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Study Assessing in Parallel Groups the Efficacy and Safety of 2 Doses of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A Treated 15 Months

Intervention Phase:

The clinical trial is currently at phase III determining the effectiveness and safetiness of PXT3003 drug (a fixed dose combination of (RS)-baclofen, naltrexone hydrochloride and D-sorbitol) as treatment for Charcot-Marie-Tooth disease type 1A (CMT1A) on children, young adults, and adults diagnosed patients.

Procedure:

Patients are randomly assigned to three treatments: PXT3003 dose 1, PXT3003 dose 2, and placebo, wherein they receive a liquid oral solution of 5 ml twice a day - morning and evening - accompanied with food for 15 months.

Goal:

The goal of the study is to assess the efficacy of PXT3003 drug on improving the overall neuropathy limitation scale (ONLS) total score of Charcot-Marie-Tooth disease type 1A.

Further details at:

https://clinicaltrials.gov/ct2/show/study/NCT02579759

References

[1] Barreto LC, Oliveira FS, Nunes PS, de França Costa IM, Garcez CA, Goes GM, Neves EL, de Souza Siqueira Quintans J, de Souza Araújo AA. Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology. 2016;46(3):157-65. doi: 10.1159/000443706. Epub 2016 Feb 6. Review.
[2] Cedars Sinai (n.d) Charcot-Marie-Tooth Disease. Retrieved from https://www.cedars-sinai.org/health-library/diseases-and-conditions/c/charcot-marie-tooth-disease.html

[3] Charcot-Marie Tooth Disease. (n.d.). Omim#606482. https://www.omim.org/entry/606482

[3] Charcot Marie Tooth News (n.d) Living with Charcot-Marie-Tooth Disease (CMT). Retrieved from https://charcot-marie-toothnews.com/living-with-charcot-marie-tooth-disease-cmt/#Helle Høyer, Geir J. Braathen, Øyvind L. Busk, Øystein L. Holla, Marit Svendsen, Hilde T. Hilmarsen, Linda Strand, Camilla F. Skjelbred, Michael B. Russell, "Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing", BioMed Research International, vol. 2014, Article ID 210401, 13 pages, 2014. https://doi.org/10.1155/2014/210401

[4] Mayo Clinic (n.d) Charcot-Marie Tooth Disease. Retrieved from https://www.mayoclinic.org/diseases-conditions/charcot-marie-tooth-disease/diagnosis-

treatment/drc-20350522#
[5] Min Zhong, Qing Luo, Ting Ye, XiDan Zhu, Xiu Chen, JinBo Liu, "Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis", BioMed Research International, vol. 2020, Article ID 1353516, 13 pages, 2020. https://doi.org/10.1155/2020/1353516

FOR INFORMATION

FOR IMAGES

[1] Charcot-Marie-Tooth disease. (2018). Health Direct. Retrieved from https://www.healthdirect.gov.au/charcot-marie-tooth-disease

[2]Delague, V. & Sandre-Giovannoli, A. (2005). Homozygosity mapping of autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy (CMT4H) to a novel locus on chromosome 12p11.21-q13.11. Journal Of Medical Genetics; 42(3):260-5. DOI: 10.1136/jmg.2004.024364

[3]Vita, G. La Foresta, S., Russo, M., et al. (2016). Sport activity In Charcot-Marie-Tooth Disease: A case study of a Paralympic swimmer. NEuromuscular Disorders; 26 (9). Pp 614-618. https://doi.org/10.1016/j.nmd.2016.06.002

[4]You, Y., Wang, X., Li, S., Zhao, X., & Zhang, X. (2018). Exome sequencing reveals a novel MFN2 missense mutation in a Chinese family with Charcot‑Marie‑Tooth type 2A. Experimental and Therapeutic Medicine, 16, 2281-2286.