Charcot-Marie-Tooth Disease

Understanding the condition

From: MedlinePlus, National Library of Medicine

Charcot-Marie-Tooth disease (CMT) is a group of genetic nerve disorders. It is named after the three doctors who first identified it. In the United States, CMT affects about 1 in 2,500 people.

CMT affects your peripheral nerves. Peripheral nerves carry movement and sensation signals between the brain and spinal cord and the rest of the body. Symptoms usually start around the teen years. Foot problems such as high arches or hammertoes can be early symptoms. As CMT progresses, your lower legs may weaken. Later, your hands may also become weak.

Doctors diagnose CMT by doing a neurologic exam, nerve tests, genetic tests, or a nerve biopsy. There is no cure. The disease can be so mild you don't realize you have it or severe enough to make you weak. Physical therapy, occupational therapy, braces and other devices and sometimes surgery can help.

Genetic causes described in the linked summary

From: MedlinePlus Genetics

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in dozens of different genes can cause Charcot-Marie-Tooth disease. These genes provide instructions for making proteins that are involved in the function of peripheral nerves. The variants that are associated with Charcot-Marie-Tooth disease can cause cells to produce proteins that do not work properly. These changes affect myelin or the axons of nerve cells and slow down or weaken nerve signals. Longer nerves that run from the spinal cord to the hands and feet are especially vulnerable. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles in the feet, legs, and hands, and to transmit sensory signals from these areas to the brain. Different variants in the same gene can lead to different types of Charcot-Marie-Tooth disease.

Pathogenic variants in the PMP22, MPZ, MFN2, and GJB1 genes account for 80 to 90 percent of the genetic causes of Charcot-Marie-Tooth disease. Most people with CMT1 have variants that affect the PMP22 gene. These cases typically occur when there is an extra copy of the gene due to a small piece genetic material on chromosome 17 being abnormally copied (duplicated). Another 5 to 10 percent of individuals with CMT1 have variants in the MPZ gene. Variants in the MFN2 gene are the most common cause of CMT2, while approximately 90 percent of people with CMTX have GJB1 gene variants.

Pathogenic variants in many other genes have been identified in smaller numbers of individuals with Charcot-Marie-Tooth disease. As research advances, the number of genes associated with Charcot-Marie-Tooth disease continues to grow.

Inheritance described in the linked summary

From: MedlinePlus Genetics

The pattern of inheritance varies depending on the type of Charcot-Marie-Tooth disease.

CMT1, most cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to cause the disorder.

CMT4, a few CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. In autosomal recessive inheritance, the parents of an affected individual each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

CMTX is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), a pathogenic variant in the only copy of the gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked variants to their sons. In females (who have two copies of the X chromosome), one altered copy of the gene generally causes milder signs and symptoms of the disorder than those seen in affected males. However, in some cases, females with CMTX may have signs and symptoms that are as severe as those in males.

About 10 percent of cases of Charcot-Marie-Tooth disease result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Which doctor should you see?

The suggested department for discussing Charcot-Marie-Tooth Disease is Dentistry, with a dentist / relevant dental specialist as the relevant type of clinician. Dentist / Relevant dental specialist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which teeth, gum tissues or oral structures are affected?
• What is the purpose of any proposed dental imaging or procedure?
• What oral-care routine is suitable while the problem is being treated?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.